Indian consensus statement for the diagnosis and

management of IPF

Making the diagnosis of IPF

Dr. Aditya Jindal

Questions
Q1. What is the importance of clinical history in the diagnosis and
differential diagnosis of DPLD?

Q2. What investigations should be done in patients suspected to have

IPF?

Q3. What is the role of pulmonary function tests and exercise testing?
Which pulmonary function tests must be carried out at the time of
diagnosis of IPF?

Q4. What investigations should be done to assess the prognosis?

Q1. What is the importance of clinical history in the diagnosis and
differential diagnosis of DPLD?
• DPLD have a wide differential diagnosis
• LVF, COPD, TB, etc
• Three step approach

St • Establish ILD diagnosis

ep
1
St • Establish primary (IIPs) vs secondary ILD
ep
2
St • Establish type of IIP
ep
3
Meyer, Translational Respiratory Medicine 2014
Meyer, Translational Respiratory Medicine 2014
 Symptoms indicative of
idiopathic pulmonary fibrosis at
baseline.

Management of patients with idiopathic pulmonary fibrosis in clinical practice: the

INSIGHTS-IPF registry. Behr et al. ERJ 2015.
Evaluation of History, Exam.,
PFT, CXR
suspected IIP Suspected ILD
HRCT
Typical features
Yes No
IPF
Secondary
Treat causes
appropriately Yes
No
Blood
Surgical lung n di a gnostic investigations,
No TBLB
biopsy

Diagnostic Diagnostic
Non diagnostic Treat as required Treat
Multidisciplinary appropriately
review
Recommendation
• A thorough clinical history and examination is an essential step in the
evaluation of patients with ILD.
Q2. What investigations should be done in patients suspected to have
IPF?

• Purpose
• To rule out differential diagnoses
• To establish the diagnosis
• To assess patient fitness for treatment/ prognosis

Laboratory tests to order in the majority of patients with interstitial lung disease

Complete blood count and differential

Liver function tests
Renal function tests
Tests for possible rheumatic disease
• Antinuclear antibody (ANA)
• Rheumatoid factor (RF)
Laboratory tests to order in selected patients with interstitial lung disease

Additional possible tests for systemic rheumatic disease

• Anti-cyclic citrullinated peptide (Anti-CCP)
• Creatine kinase (CK), aldolase
• Anti-Jo-1 antibody
• Anti-neutrophil cytoplasmic antibody (ANCA)
• Anti-topoisomerase (Scl-70) antibody, anti-PM-1 (PM-Scl) antibody
• Anti-double stranded (ds) DNA antibodies

Sicca features or positive anti-extractable nuclear antigen (ENA): Check anti-RO (SS-A), anti-La (SS-B), anti-
ribonucleoprotein (RNP), serum protein electrophoresis, serum IgG4
Sclerodactyly, prominent GERD: Check anti-centromere, anti-topoisomerase I (anti-Scl-70)
Mechanics hands: Antisynthetase antibodies (in addition to anti-Jo-1)
Suspicion of heart failure or pulmonary hypertension: Brain natriuretic peptide (BNP) or N-terminal proBNP (NT-
proBNP)
Anemia and/or hemoptysis: Coagulation studies, anti-glomerular basement membrane (GBM) antibodies,
antiphospholipid antibodies, serum IgA endomysial or tissue transglutaminase antibodies in patients who may have
idiopathic pulmonary hemosiderosis
Risk factors for HIV: HIV test
Testing for hypersensitivity pneumonitis antibodies based on patient exposures

Fisher et al. ERS-ATS research statement: interstitial pneumonia with autoimmune features Eur Respir
J 2015
• Other investigations
• Chest X-ray – More helpful for ruling out alternative diagnoses

• To rule out cardiac disease

• ECG
• Serum brain natriuretic peptide or N-terminal-proBNP
• Doppler echocardiography
• Right heart catheterization in patients with normal echocardiogram but high clinical
suspicion for pulmonary hypertension

• HRCT thorax
to be discussed in the next session
• Histopathology
Recommendation
• Relevant targeted investigations may be done after clinical evaluation
to establish the diagnosis of IPF and to rule out alternative diagnoses.
Q3. What is the role of pulmonary function tests and exercise
testing? Which pulmonary function tests must be carried out at the
time of diagnosis of IPF?
• Spirometry, lung volumes, diffusing capacity and pulse oximetry should be
obtained in virtually all patients with suspected interstitial lung disease

• Lung function is most helpful for assessing the severity of lung involvement and
the pattern, whether obstructive, restrictive, or mixed

• PFTs are helpful in narrowing the differential diagnosis, assessing the severity and
prognosis of the disease and in following up the patient
• Most of the interstitial disorders have a restrictive defect with reductions in total
lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV)
• FEV1/FVC ratio is usually normal or increased

• Interstitial pattern on chest radiograph accompanied by obstructive airflow

limitation is suggestive of any of the following
• Sarcoidosis
• Hypersensitivity pneumonitis
• Pulmonary Langerhans cell histiocytosis
• Tuberous sclerosis and pulmonary lymphangioleiomyomatosis
• Combined chronic obstructive pulmonary disease (COPD) and ILD
• Constrictive bronchiolitis
• Longitudinal changes in DLCO and FVC have been used to assess disease
progression or regression.
• Due to difficulties with reproducibility in measuring DLCO, a change of 15% is
needed to identify a true change in disease severity while a change of 10%
suffices for FVC
• For the initial assessment DLCO values provide better prognostic information
while changes in FVC more consistently predicts mortality on follow up

• Desaturation during the 6MWT has been shown to strongly associated with
prognosis, both at diagnosis and follow up
• Maximal exercise testing does not provide superior information in the routine
clinical setup
Wells et al. Interstitial lung disease BTS guidelines. Thorax 2008
Latsi et al. AJRCCM 2003
Raghu et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based
Guidelines for Diagnosis and Management. AJRCCM 2011
Recommendation
• Standard spirometry should be done in the evaluation of the majority
of patients suspected to have IPF
Q4. What investigations should be done to assess the prognosis?

Raghu et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-

based Guidelines for Diagnosis and Management. AJRCCM 2011
• Biomarkers
• Surfactant proteins A and D (SP-A and SP-D)
• KL-6
• Lactate dehydrogenase (LDH)
• CCL-18

• Sufficient data not yet available

Thomeer et al. Clinical use of biomarkers of survival in pulmonary fibrosis Respiratory Research
2010
Kaplan–Meier survival
curve examining long-term
oxygen
therapy (LTOT) initiation at
baseline

Sharp C, Adamali HI, Millar AB. A comparison of published multidimensional indices to predict
outcome in idiopathic pulmonary fibrosis. ERJ Open Res 2017
Multidimensional indices: baseline values and univariable Cox regression hazard ratios

Sharp C, Adamali HI, Millar AB. A comparison of published multidimensional indices to predict
outcome in idiopathic pulmonary fibrosis. ERJ Open Res 2017;
Recommendation
• Clinical evaluation and lung function testing are currently the best
methods to assess the prognosis of IPF in the clinical scenario