IDIOPATHIC PULMONARY FIBROSIS (IPF)

ADETUNJI T.A.Dept Of Medicine

OAUTHC Ile-Ife

OUTLINE• INTRODUCTION• CLASSIFICATION• EPIDEMIOLOGY• AETIOLOGY• PATHOPHYSIOLOGY• CLINICAL FEATURES• DIAGNOSIS• DIFFERENTIALS• COMPLICATIONS• PROGNOSIS• CONCLUSION• REFRENCES

INTRODUCTION

• Idiopathic pulmonary fibrosis (IPF) a.k.a cryptogenic fibrosing alveolitis, is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause,– primarily occurring in older adults, – limited to the lungs, – associated with histopathologic and/or radiologic pattern of

usual interstitial pneumonia (UIP)• IPF portends a poor prognosis • No proven effective therapies are available for its

treatment beyond lung transplantation.

INTODUCTION2

• IPF is an interstitial lung disease (ILD)• ILDs represent a large number of conditions that

involve the parenchyma of the lung—the alveoli, the alveolar epithelium, the capillary endothelium, and the spaces between these structures, as well as the perivascular and lymphatic tissues.

• Heterogeneous group of disorders classified together because of similar clinical, roentgenographic, physiologic, or pathologic manifestions

CLASSIFICATION

• ILD can be broadly classified based on major histo-pathological finding into(1) those associated with predominant inflammation

and fibrosis and (2) those with a predominantly granulomatous

reaction • Each can be subdivided into– Known cause– Unknown cause

Inflammation/Fibrosis

Known Cause • Asbestosis• Fumes, gases• Drugs (antibiotics,

amiodarone, gold) and chemotherapy drugs

• Radiation• Aspiration pneumonia• Residual of acute

respiratory distress syndrome

• Smoking-related– Desquamative

interstitial pneumonia (DIP)

– Respiratory bronchiolitis–associated interstitial lung disease

– Langerhans cell granulomatosis (eosinophilic granuloma of the lung)

Inflammation/Fibrosis

• Unknown Cause• Idiopathic interstitial

pneumonias (IIP)– Idiopathic pulmonary

fibrosis– Acute interstitial

pneumonia– Cryptogenic organizing

pneumonia (bronchiolitis obliterans with organizing pneumonia)

– Nonspecific interstitial pneumonia

• Connective tissue diseases– Systemic lupus

erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren's syndrome, polymyositis-dermatomyositis

• Pulmonary hemorrhage syndromes– Goodpasture's syndrome,

idiopathic pulmonary hemosiderosis, isolated pulmonary capillaritis

Inflammation/Fibrosis

• Lymphocytic infiltrative disorders (lymphocytic interstitial pneumonitis assd with CTD)

• Eosinophilic pneumonias• Lymphangioleiomyomatosis• Amyloidosis• Inherited diseases

– Tuberous sclerosis, neurofibromatosis, Niemann-Pick disease, Gaucher's disease, Hermansky-Pudlak syndrome

• Gastrointestinal or liver diseases (Crohn's disease, primary biliary cirrhosis, chronic active hepatitis, ulcerative colitis)

• Graft-versus-host disease (bone marrow transplantation; solid organ transplantation)

Granulomatous

Known Cause • Hypersensitivity

pneumonitis (organic dusts)

• Inorganic dusts: beryllium, silica

• Unknown cause• Bronchocentric

granulomatosis

• Lymphomatoid granulomatosis

• Sarcoidosis• Granulomatous

vasculitides• Langerhans' cell

granulomatosis • Wegener's granulomatosis • Allergic granulomatosis of

Churg-Strauss

EPIDEMIOLOGY

• IPF is the commonest of all Idiopathic Interstitial Pneumonias (IIPs)

• Worldwide incidence– 10.7 cases per 100,000 person-years for males and 7.4

cases per 100,000 person years for females.• Worldwide prevalence– 20 cases per 100,000 persons for males and 13 cases per

100,000 persons for females.

• Kim DS, Collard HR, King TE., Jr Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc

2006;3:285–92.

EPIDEMIOLOGYUSA• Age and sex adjusted incidence

– 8.8-17.4 per 100,000 person-years a

• Prevalence– 27.4-63/100,000 person years a

• Nigeria – case reportb

• a-Fernandez Perez ER, Daniels CE, Schroeder DR, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. Jan 2010;137(1):129-37• b-A rare case of cor pulmonale secondary to idiopathic pulmonary fibrosis in Nigeria Raphael Chinedu Anakwue et al

EPIDEMIOLOGY

• Age– >50yrs

• Sex prevalence– >M:F (55yrs and older)

• Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Oct 1 2006;174(7):810-6

AETIOLOGY

• Remains undefined• However, some inciting agents have been

implicated– Cigarette smoking– Smoke– Environmental pollutants– Viral infections– Gastroesophageal reflux disease– Chronic aspiration– Genetic basis : <5%

PATHOGENESIS

• Previous theory - generalized inflammation progressed to widespread parenchymal fibrosis.

• Current theory - IPF is an epithelial-fibroblastic disease, in which unknown endogenous or environmental stimuli disrupt the homeostasis of alveolar epithelial cells, resulting in diffuse epithelial cell activation and aberrant epithelial cell repair.

Re-establishing an intact epithelium following injury is a key component of normal wound healing.

PATHOGENESIS

• In IPF, exposure to an inciting agent in a susceptible host may lead to the initial alveolar epithelial damage

• Following injury, aberrant activation of alveolar epithelial cells leading to– 1) release of potent fibrogenic cytokines and growth

factors, eg. TNF-α, TGF-β, platelet-derived growth factor, insulin-like growth factor-1, ET-1

– These are involved in the migration and proliferation of fibroblasts and the transformation of fibroblasts into myofibroblasts

PATHOGENESIS

– 2) provokes the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci

– myofibroblasts secrete extracellular matrix proteins

PATHOGENESIS

• Failure of apoptosis leads to myofibroblast accumulation, exuberant extracellular matrix protein production, persistent tissue contraction, and pathologic scar formation

PATHOGENESIS

• TGF-β has been shown to promote an antiapoptotic phenotype in fibroblasts

• Research has shown that apoptosis resistance in the fibroblasts and myofibroblasts participating in the repair of the alveolar epithelium may contribute to the persistent and/or progressive fibrosis in idiopathic pulmonary fibrosis.

PATHOGENESIS

Genetic basis– Mutant telomerase

• Telomerase is a specialized polymerase that adds telomere repeats to the ends of chromosomes, helping to offset shortening that occurs during DNA replication.

• TGF-β negatively regulates telomerase activity- mutation

PATHOGENESIS

• This telomere shortening could promote the loss of alveolar epithelial cells, resulting in aberrant epithelial cell repair, and therefore should be considered as another potential contributor to the pathogenesis of idiopathic pulmonary fibrosis

PATHOGENESIS– MUC5B– Mucin 5B is a protein that is encoded MUC5B gene

• A common variant in the putative promoter of the gene that encodes mucin 5B (MUC5B) has been associated with the development of both familial interstitial pneumonia and sporadic pulmonary fibrosis.

• MUC5B expression in the lung was reported to be 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not.

• Therefore, dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis.

PATHOGENESIS

– Surfactant protein C• Genetic mutations in serum surfactant protein

C have been discovered in some individuals with familial pulmonary fibrosis.

• These mutations in serum surfactant protein C may damage type II alveolar epithelial cells

PATHOGENESIS

– Caveolin-1• Caveolin-1 limits TGF-β–induced production of

extracellular matrix proteins and restores the alveolar epithelial-repair process.

• It has been observed that the expression of caveolin-1 is reduced in lung tissue from patients with idiopathic pulmonary fibrosis.

CLINICAL FEATURES

• SYMPTOMS• Gradual onset, often

greater than 6 months, of dyspnea – exertional, progressive

• and/or a nonproductive cough

Systemic symptoms (uncommon)

• Weight loss• Low-grade fevers• Fatigue• Arthralgias• Myalgias

CLINICAL FEATURES

• Approximately 5% of patients are asymptomatic at diagnosis – routine chest radiograph/lung biopsy

• In these group however, symptoms developed approximately 1000 days after the recognition of the radiographic abnormality a

• a-Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):285-92.

CLINICAL FEATURES

• It is critical to obtain a complete history, including – medication history – amiodarone, bleomycin,

nitrofurantoin– social history– occupational history– exposure history– Review of systems

• To exclude other causes of interstitial lung disease.

CLINICAL FEATURES

SIGNS• Evidence of respiratory distress• fine bibasilar inspiratory crackles (Velcro

crackles). • digital clubbing(25-50%)• Cyanosis • Aside features of pulm HTN/cor pulmonale,

extra pulmonary involvement does not occur with idiopathic pulmonary fibrosis

Clubbing of the fingers in idiopathic pulmonary fibrosis

CLINICAL FEATURES

• FEATURES OF PULM HTN (20-40%)– loud P2 – fixed split S2, – holosystolic tricuspid regurgitation murmur,– pedal edema.– right ventricular heave– elevation of the jugular venous pressure

DIAGNOSIS

• If IPF is suspected, diagnosis can be challenging

DIAGNOSIS

• A Multidisciplinary Consensus Statement on the Idiopathic Interstitial Pneumonias published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2000 proposed specific major and minor criteria for establishing the diagnosis of IPF.

• However, in 2011, new simplified and updated criteria for the diagnosis and management of IPF were published by the ATS, ERS, together with the Japanese Respiratory Society (JRS) and Latin American Thoracic Association (LATA)

DIAGNOSIS

Currently, a diagnosis of IPF requires:• Exclusion of known causes of ILD, e.g., domestic

and occupational environmental exposures, connective tissue disorders, or drug exposure/toxicity

• The presence of a typical radiological Usual Interstitial Pneumonia (UIP) pattern on HRCT.

• Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy

IMAGING

High-resolution computed tomography• an essential component of the diagnostic

pathway in IPF• IPF is characterized by patchy, predominantly

peripheral, predominantly subpleural, and bibasilar reticular opacities

• Subpleural honeycombing (< 5-mm round translucencies with a density equal to that of air) is also a common finding

Classic subpleural honeycombing (red circle) in a patient with a diagnosis of idiopathic pulmonary fibrosis

IMAGING

• Ground-glass opacities can be found but are less extensive than reticular abnormalities.

• Traction bronchiectasis could also be found

A patient with IPF and a confirmed histologic diagnosis of usual interstitial pneumonia. Note the reticular opacities (red circle) distributed in both lung bases and the minimal ground-glass opacities (blue circle)

High-resolution computed tomography scans of the chest of a patient with IPF. The main features are of a peripheral, predominantly basal pattern of coarse reticulation with honeycombing

IMAGING

• Reticular opacities and honeycombing seen on HRCT imaging correlates histologically with fibrosis and honeycombing.

• The presence of subpleural honeycombing, traction bronchiectasis, and thickened interlobular septae increase the specificity of HRCT for diagnosing idiopathic pulmonary fibrosis

IMAGING

• Multiple studies have documented that the accuracy of a confident diagnosis of usual interstitial pneumonia made on the basis of HRCT imaging findings by an experienced observer exceeds 90%a

• a-Misumi S, Lynch DA. Idiopathic pulmonary fibrosis/usual interstitial pneumonia: imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. Jun 2006;3(4):307-14.

IMAGING

HRCT Criteria for UIP Pattern:

– UIP pattern requires all 4 features below.• Subpleural, basal predominance• Reticular abnormality• Honeycombing with or without traction

bronchiectasis• Absence of features listed as inconsistent with

UIP pattern

IMAGING

Inconsistent with UIP pattern requires any of the 7 features below.– Upper or mid-lung predominance– Peribronchovascular predominance– Extensive ground-glass abnormality (extent greater than

reticular abnormality)– Profuse micronodules (bilateral, predominantly upper lobes)– Discrete cysts (multiple, bilateral, away from areas of

honeycombing)– Diffuse mosaic attenuation/air-trapping (bilaterally, in 3 or more

lobes)– Consolidation in bronchopulmonary segment(s)/lobe(s)

IMAGING

Chest Radiography• Virtually all patients with IPF have an

abnormal chest radiograph at the time of diagnosis

• lacks diagnostic specificity for idiopathic pulmonary fibrosis.

IMAGING

The typical findings :• Peripheral reticular opacities (netlike linear

and curvilinear densities) predominantly at the lung bases.

• Honeycombing (coarse reticular pattern) and lower lobe volume loss can also be seen.

Chest radiograph of a patient with idiopathic pulmonary fibrosis showing bilateral lower lobe reticular opacities (red circles)

A chest radiograph of a patient with IPF. Note the small lung fields and peripheral pattern of reticulonodular opacification

OTHER TESTS

Pulmonary function testing• Findings are nonspecific and should be used in

conjunction with clinical, radiologic, and pathologic information to ensure an accurate diagnosis

• Good for prognostication

• Ventilatory pattern – Restrictive– Vital capacity, functional residual capacity, total lung

capacity, and forced vital capacity (FVC) all are reduced

– Obstructive ventilatory defect, not common; if present, may suggest the coexistence of COPD.

• Diffusion Capacity of Carbon monoxide (DLco) – Reduced– In IPF, reduced DLCO may precede the development

of abnormal lung volumes

6-Minute walk testing (6MWT)• marker of functional exercise capacity that is

being increasingly used in the initial and longitudinal clinical assessment of patients with idiopathic pulmonary fibrosis

• Markers of increased mortality– Patients who have >10% decline in FVC (percent

predicted) over 6 months, have a 2.4-fold increased risk of death.

– Baseline DLCO below 35% is correlated with increased mortality.

– So also decline in DLCO greater than 15% over 1 year– Desaturation below the threshold of 88% during the

6MWT

Note:• in patients who do not desaturate to less than

88% during a 6-minute walk test (6MWT), the only strong predictor of mortality is a progressive decline in FVC (>10% after 6 mo)

• in patients who desaturate to less than 88% during a 6MWT, a progressive decline in DLCO (>15% after 6 mo) is a strong predictor of increased mortality

• Bronchoalveolar Lavage (BAL)– not required for the diagnosis of IPF– can be useful to exclude other alternative diagnoses– may demonstrate the presence of infection,

malignancy, alveolar proteinosis, eosinophilic pneumonia, or occupational dusts.

BAL fluid neutrophilia has been demonstrated to predict early mortality.

Diagnostic Value of Bronchoalveolar Lavage in Interstitial Lung Disease

Condition Bronchoalveolar lavage finding

Sarcoidosis Lymphocytosis; CD4:CD8 ratio >3.5 most specific of diagnosis

Hypersensitivity Pneumonitis Marked lymphocytosis (>50%)

Organizing Pneumonia Foamy macrophages; mixed pattern of increased cells characteristic; decreased CD4:CD8 ratio

Eosinophilic lung disease Eosinophils > 25%

Diffuse alveolar bleeding Hemosiderin-laden macrophages, red blood cells

Diffuse alveolar damage – drug toxicity

Atypical hyperplastic type II pneumocytes

Opportunistic infections Pneumocystis carinii, fungi, cytomegalovirus-transformed cells

Lymphangitic carcinomatosis, alveolar cell carcinoma, pulmonary lymphoma

Malignant cells

Diagnostic Value of Bronchoalveolar Lavage in Interstitial Lung Disease

Condition BAL findings

Alveolar proteinosis Milky effluent, foamy macrophages and lipoproteinaceous intraalveolar material (periodic acid–Schiff stain–positive)

Lipoid pneumonia Fat globules in macrophages

Pulmonary Langerhans Cell Histiocytosis

Increased CD1+ Langerhans cells, electron microscopy demonstrating Birbeck granule in lavaged macrophage (expensive and difficult to perform)

Asbestos-related pulmonary disease

Dust particles, ferruginous bodies

Berrylliosis Positive lymphocyte transformation test to beryllium

Silicosis Dust particles by polarized light microscopy

Lipoidosis Accumulation of specific lipopigment in alveolar macrophages

• Transthoracic Echocardiography – pulm HTN, • ECG – pulmonary HTN• Up to 30% of patients with IPF have positive

tests for ANA or rheumatoid factor; however, these titers are generally not high.– Presence of high titers may suggest the presence

of a connective-tissue disease. • CRP, ESR – may be elevated (60-94%)

LUNG BIOPSY

• According to the updated 2011 guidelines, in the absence of a typical UIP pattern on HRCT, a surgical lung biopsy is required for confident diagnosis

i.e, in patients with possible UIP pattern or inconsistent with UIP pattern

• Histologic specimens for the diagnosis of IPF must be taken at least in three different places and be large enough that the pathologist can comment on the underlying lung architecture

• Hence, surgical lung biopsy specimen are obtained through either an open lung biopsy or video-assisted thoracoscopic surgery (VATS)

HISTOLOGY• The histopathological lesion associated with

idiopathic pulmonary fibrosis is -Usual interstitial pneumonia(UIP).

• characterized by a heterogeneous, variegated appearance with alternating areas of healthy lung, interstitial inflammation, fibrosis, and honeycomb change

• resulting in a patchwork appearance at low magnification

Photomicrograph of the histopathological appearances of usual interstitial pneumonia. High-power magnification (on the right) shows a focus of fibroblastic proliferation, close to an area of fibrosis within which a mild, non-specific, chronic inflammatory cell infiltrate can be observed. In the subpleural space, a typical honeycombing aspect can be recognized.

• Fibrosis predominates over inflammation in usual interstitial pneumonia

• Fibroblastic foci represent microscopic zones of acute lung injury and are randomly distributed within areas of interstitial collagen deposition and

• Consist of fibroblasts and myofibroblasts arranged in a linear fashion within a pale-staining matrix.

• they represent an important diagnostic criterion

UIP pattern requires all 4 criteria below.• Evidence of marked fibrosis/architectural

distortion and/or honeycombing in a predominantly subpleural/paraseptal distribution

• Presence of patchy involvement of lung parenchyma by fibrosis

• Presence of fibroblast foci• Absence of features against a diagnosis of UIP

suggesting an alternate diagnosis

• Probable UIP pattern requires the following:– Evidence of marked fibrosis/architectural

distortion and/or honeycombing– Absence of either patchy involvement or

fibroblastic foci, but not both– Absence of features against a diagnosis of UIP

suggesting an alternate diagnosisOR– Honeycombing changes only

• Possible UIP pattern requires all 3 criteria. – Patchy or diffuse involvement of lung parenchyma

by fibrosis, with or without interstitial inflammation

– Absence of other criteria for UIP– Absence of features against a diagnosis of UIP

suggesting an alternate diagnosis

• Not UIP pattern requires any of the 6 criteria.– Hyaline membranes– Organizing pneumonia– Granulomas– Marked interstitial inflammatory cell infiltrate

away from honeycombing– Predominant airway centered changes– Other features suggestive of an alternate

diagnosis

Diagnostic Considerations

• IPF– possible UIP pattern on HRCT and – UIP pattern or probable UIP pattern on surgical

lung biopsy• Probable IPF– possible UIP pattern on HRCT and – possible UIP pattern or non-classifiable fibrosis on

surgical lung biopsy

• Possible IPF– a pattern inconsistent with UIP on HRCT and– UIP pattern on surgical lung biopsy

• Not IPF– a pattern inconsistent with UIP on HRCT and– probable UIP/possible UIP/ nonclassifiable fibrosis

on surgical lung biopsy– Any pattern on HRCT associated with a surgical

lung biopsy finding of not UIP

DIFFERENTIAL DIAGNOSIS

• These are numerous. A few include• Other Idiopathic Interstitial Pneumonias (IIPs)– nonspecific interstitial pneumonia,– cryptogenic organizing pneumonia, – acute interstitial pneumonia– lymphoid interstitial pneumonia

DIFFERENTIAL DIAGNOSIS

• Other causes of UIP pattern– Systemic sclerosis/Scleroderma– Hypersensitivity Pneumonitis– Rheumatoid Arthritis– Fibronodular Sarcoidosis– Asbestosis– Drug induced fibrosis

DIFFERENTIAL DIAGNOSIS

• Other causes of Ground Glass Appearance on HRCT– Heart Failure– Non Specific Idiopathic Pneumonia (NSIP)– Desquamative Interstitial Pneumonia– Hypersensitivity Pneumonitis

TREATMENT

Can be divided into

Non-pharmacologic

Pharmacologic

Surgical

TREATMENT

Non-pharmacologic• Smoking cessation• Diet: healthy diet/ideal body weight improves

QOL• Long term Oxygen therapy – when SpO2<88%

or PaO2< 55mmHg• Vaccination against influenza and

pneumoccocal infections

TREATMENT

Pharmacologic• Novel approaches to treatment are being

developed based on the new theories of IPF pathogenesis

• No optimal medical treatment of IPF is yet to be identified

• Hence, risk-benefit ratio important.

TREATMENT

Antioxidants• N-acetyl cysteine (NAC) – gluthathione

precursor• Study of the Effects of High-Dose N-

Acetylcysteine (NAC) in IPF (IFIGENIA Idiopathic Pulmonary Fibrosis International Group Exploring N-Ace-tylcysteine I Annual)– showed improvement in Dlco and VC over 12

months of follow up

TREATMENT

• Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF(PANTHER-IPF) however, worsened outcome, and increased admission rate

Biological response modulators• Etanercept (anti TNF-alpha) – no improvementEndothelin receptor antagonists• Bosentan showed no improvement in 6MWT

over placebo

TREATMENT

Phosphodiesterase inhibitors• Sidenafil - no significant difference in the

6MWT• However, statistically significant differences in

the change in dyspnea, PaO2, diffusing capacity, and quality of life were noted.

TREATMENT

Tyrosine kinase inhibitors• Imatinib mesylate: potent inhibitor of lung

fibroblast-myofibroblast transformation and proliferation, through inhibition of platelet-derived growth factor and transforming growth factor-β signaling – showed no significant improvement in lung function over placebo

TREATMENT

Antifibrotic agents• Pirfenidone(Esbriet): a novel compound with

combined anti-inflammatory, antioxidant, and antifibrotic effects – first approved in Japan

• Approved by USA FDA in Oct 15 2014• Colchicine: no improvement in clinical

outcomeAnticoagulant: worsened outcome

TREATMENT

Surgical• Lung transplantation – definitive treatment– Any patient diagnosed with IPF or probable IPF should be

referred for lung transplantation evaluation, regardless of the vital capacity

• Indication for listing– DLCO <39% predicted, – 10% or greater decrement in FVC during 6 months of follow-

up, – decrease in pulse oximetry below 88% during a 6MWT– or honeycombing on HRCT imaging

COMPLICATIONS

Acute exacerbation of IPF (AE-IPF)• Commonest/most dreaded• Worsens prognosis• Rate – 10-57%• Usually secondary to infections, pulmonary

embolism, or pneumothorax

COMPLICATIONS

Diagnostic criteria for an AE-IPF:• Previous or concurrent diagnosis of idiopathic pulmonary fibrosis• Unexplained worsening or development of dyspnea within 30

days• HRCT scan with new bilateral ground-glass abnormality and/or

consolidation superimposed on a background reticular or honeycomb pattern consistent with a usual interstitial pneumonia pattern

• Worsening hypoxemia from a known baseline arterial blood gas measurement

• No evidence of pulmonary infection by endotracheal aspiration or BAL

OTHER COMPLICATIONS

• Pulmonary hypertension• Respiratory infection• Acute coronary syndrome• Thromboembolic disease• Adverse medication effects• Lung cancer

PROGNOSIS

• Prognosis is poor• 5yr survival rate – 20-40%Poor prognostic factors

– >10% decline in FVC (% predicted) over 6 months– DLCO <35%

– A decline in DLCO >15% over 1 year – Desaturation below the threshold of 88% during the 6MWT– Progressive decline in DLCO (>15% after 6 mo)– BAL fluid neutrophilia – Male sex– Age >65

CONCLUSION

• IPF is a chronic progressive fibrosing IP • Aetiology is unknown • It’s uncommon but invariably fatal• Bears semblance to a host of other disease entities• Diagnosis relies on the clinician integrating the clinical,

laboratory, radiologic, and/or pathologic features to make a clinical-radiologic-pathologic correlation that supports its diagnosis.

• No proven effective medical therapy save lung transplantation.

REFERENCES

• Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. Mar 15 2011;183(6):788-824.].

• American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. Jan 15 2002;165(2):277-304.

REFERENCES

• du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. Dec 15 2011;184(12):1382-9

• Wikipedia online• Medscape online• Harrison’s textbook of clinical medicine

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