Key Clinical Summary: Recognising Early Pulmonary Fibrosis and Accelerating Diagnosis
This is a micro-learning module summary of Prof. Corey Kershaw’s session which you can find here. Before participating, please read our CME and disclosure information which can be found here.
Acknowledgment: This activity is supported by an educational grant from This program is supported by an independent educational grant from Bristol Myers Squibb (BMS). This online education program has been designed solely for healthcare professionals in the USA. The content is not available for healthcare professionals in any other country.
Introduction
This session, led by Corey Kershaw, explored the practical steps clinicians must take to recognise early pulmonary fibrosis, distinguish idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases (ILDs), and accelerate accurate diagnosis. Using a representative clinical case, the session highlighted how history, imaging, serology, and multidisciplinary review integrate to form a confident diagnosis and guide timely management.
Case Overview: Mr. Rice
Mr. Rice, a 70-year-old former attorney with a 30-pack-year smoking history, presented with a long-standing dry cough and gradually worsening exertional dyspnoea. Symptoms had progressed subtly over more than two years, with reduced exercise tolerance and breathlessness during daily activities such as showering. Initial evaluations for allergy and cardiac disease were unrevealing. He reported no relevant environmental exposures, no concerning medications, and no family history of ILD.
On exam, the only notable finding was fine bibasilar crackles. Blood work for connective tissue disease was negative. Pulmonary function tests revealed a FVC below normal (2.73 L/69%) and reduced diffusing capacity (DLCO 48% predicted).
Understanding Idiopathic Pulmonary Fibrosis
IPF is defined as a chronic fibrosing ILD characterised by a radiologic or histopathologic usual interstitial pneumonia (UIP) pattern in the absence of an identifiable cause, such as environmental factors ascribed to ILD, associated connective tissue disease or other know causes of ILD. Risk factors include older age, male sex, and a history of smoking. Incidence varies by geography and is highest in South Korea, the United States, and Canada.
Disease progression is heterogeneous. Some patients follow a slow, steady decline; others progress rapidly or experience acute exacerbations that lead to irreversible functional loss.
The central mechanism is aberrant epithelial repair following an unknown alveolar epithelial cell injury. This aberrant healing results in progressive fibrosis that often is irreversible, especially in the case of IPF. Multiple profibrotic pathways (e.g., TGF-β, PDGF, IL-13) become activated, driving fibroblast proliferation and extracellular matrix deposition. Genetic susceptibility (e.g., MUC5B promoter variant, telomere dysfunction) contributes to abnormal healing.
Differential Diagnosis Within ILD
There are many different ILDs and providers need to make sure they identify what type of ILD they are dealing with as soon as possible to ensure optimal outcomes. A key early step is distinguishing IPF from:
- ILDs of known cause (environmental, occupational, medication-induced)
- Autoimmune-associated ILD
- Granulomatous ILDs such as sarcoidosis
- Other idiopathic interstitial pneumonias (NSIP, DIP, RB-ILD, AIP, COP, PPFE)
Within idiopathic ILD there are some major phenotypes:
- Smoking-related ILD
- Acute ILD
- Fibrosing ILDs, that include IPF
Because UIP is a pattern, not a diagnosis, clinicians must exclude alternative causes before diagnosing IPF.
The Central Role of Clinical History
A detailed history remains one of the most powerful diagnostic tools to identify the type of ILD that a patient might have. Clinicians should explore:
- Type of symptoms: dyspnea, dry cough
- Symptom onset and progression: acute or insidious - insidious dyspnoea and chronic dry cough (weeks to months) suggest IPF
- Occupational and environmental exposures: mould, birds, water damage, woodworking, composting
- Smoking history
- Past and current medications with known pulmonary toxicity, such as amiodarone, nitrofurantoin, cancer or autoimmune disease treatment
- Autoimmune symptoms: arthritis, rashes, dysphagia, recurring fevers, Raynaud's
Isolated autoantibody positivity in connective tissue disease serology is insufficient for diagnosis; clinical correlation and rheumatology input are essential.
HRCT Interpretation: Identifying UIP
The last diagnostic algorithm for IPF published in 2022 provides a step-by-step framework for IPF diagnosis. Here, after the review of all the potential causes and the associated conditions that might cause ILD, we need to consider a high-resolution chest CT scan (HRCT) is pivotal in diagnosis. This, along with the medical history is one of the most important components of IPF diagnosis.
Radiologists typically classify HRCT findings using one of four standard categories: definite UIP, probable UIP, indeterminate for UIP, or an alternate diagnosis.
A definite UIP pattern includes:
- Subpleural and basal predominance: apical-to-basal gradient
- Abnormal reticulation
- Honeycombing with or without traction bronchiectasis
- Absence of features inconsistent with UIP (e.g., cysts, micronodules, extensive ground glass, aberrant distribution)
When these features are present, concordance with surgical biopsy is 90–100%, meaning biopsy is not recommended, as described in the latest iteration of the IPF guidelines.
A probable UIP pattern includes the same feature but without the honeycombing. If you see three out of the four categories it is also very likely that the UIP will be seen in surgical biopsy (80-85%), and similarly, lung biopsy is not recommended either.
IPF is UIP but not UIP are IPF
It is important to note that IPF is considered UIP without a cause as there are other instances of UIP pattern that can be explained by something different such as exposure to asbestos, drug toxicity, hypersensitivity pneumonitis, radiation fibrosis or SARDs.
Progressive Pulmonary Fibrosis (PPF)
PPF refers to non-IPF ILDs that demonstrate worsening despite appropriate management. A patient meets PPF criteria when any two of the following occur within 12 months:
- Worsening respiratory symptoms
- Physiological progression (by PFTs, either of the following)
- Absolute decline in FVC ≥5% predicted with 1 year
- Absolute decline in DCLCO ≥10% predicted with 1 year
- Radiologic progression (by HRCT)
- More fibrotic changes such as reticulations or honeycombing fibrosis
- Increased lobar volume loss that can be explained by increased fibrosis
PPF progresses at a rate comparable to untreated IPF, as shown by data from the INPULSIS and INBUILD trials, highlighting its prognostic importance.
Diagnostic Procedures Beyond HRCT
Bronchoalveolar lavage is useful only to exclude alternative diagnoses (e.g., infection, eosinophilic pneumonia, sarcoidosis). Bronchoscopic cryobiopsy may be considered for non-UIP patterns but must be interpreted within a multidisciplinary discussion that includes a pulmonologists, a thoracic radiologist and a thoracic histopathologist.
Final Diagnosis for Mr. Rice
Mr. Rice’s HRCT showed a definite UIP pattern with no secondary cause identified through history, serology, or exam. He therefore meets criteria for idiopathic pulmonary fibrosis. Early recognition allowed prompt diagnosis without unnecessary invasive procedures.
Key Takeaways
- Early recognition of pulmonary fibrosis depends on integrating symptoms, history, HRCT pattern, and exclusion of other causes.
- UIP is a pattern; IPF is the diagnosis made only when no cause is found.
- HRCT features consistent with definite or probable UIP should avoid surgical biopsy.
- PPF represents a high-risk, progressive phenotype across non-IPF ILDs.
- Multidisciplinary discussion remains the gold standard for complex or uncertain cases.
Content is accurate as of the date of release on 6 January 2026.