2022 guidelines¹:

• Definite fibrotic disease on high-resolution computed tomography (HRCT), particularly UIP or UIP-like patterns;
• Objective evidence of progression, even if modest (e.g., ≥5% relative forced vital capacity [FVC] decline, diffusing capacity for carbon monoxide [DLCO] decline, or radiologic progression); or
• High-risk baseline features where progression is likely.

On the contrary, for patients with non-UIP diagnosis, I try to obtain more information with serologies and sampling, including bronchoscopy with bronchoalveolar lavage (BAL) or tissue biopsy, to direct therapy to disease specific conditions. I often use a time-limited therapeutic trial with predefined reassessment points.

Q. How do you approach treatment selection, and what practical factors influence antifibrotic versus immunosuppressive or combination strategies

As above, I focus on the dominant process at that moment in time; fibrosis, inflammation, or a mixture of both.

• Antifibrotic therapy is favoured when fibrosis is dominant, particularly with UIP-like patterns or PPF, regardless of the underlying diagnosis.
• Immunosuppression is favoured when there is a strong inflammatory signal—ground-glass opacity (GGO) out of proportion to fibrosis, autoimmune features, or prior steroid responsiveness.
• Combination therapy is considered when disease is clearly mixed or when progression continues despite appropriate monotherapy.

In clinical practice, treatment choice is often related to patient factors, such as side effect profile, tolerability, comorbidities, infection risk, insurance approval, etc.  I would present the data, allow patients and caregivers to make meaningful decisions, and decide on individual patient goals rather than radiologic or biopsy pattern alone.

Q. Once treatment is started, how do you assess response and decide on continuation or modification?

I emphasize early and repeatedly that response does not mean improvement. If you look at the new clinical trials published, those on antifibrotics still have lung function decline explaining the unmet need for future therapy. Therefore, in fibrotic ILD, stability is a success. I assess response using:

• Symptom trajectory;
• Longitudinal pulmonary function test (PFT) trends, rather than single data points;
• Functional measures and oxygen needs; and
• Imaging, only when clinical data is discordant.

If lung function stabilizes or decline slows, I consider therapy effective. Continued progression prompts reassessment of adherence, comorbidities, and whether combination therapy is needed. We also emphasize continued pulmonary rehabilitation, assessment for clinical trial and lung transplant evaluation.

Q. For how long should therapy be continued, and how do you revisit treatment goals?

For antifibrotics, my default is long-term continuation, as long as the patient tolerates therapy and there is evidence of stabilization or slowed decline. There is no predefined “stop date.”

Immunomodulatory therapy is reassessed more frequently, with an emphasis on:

• Early steroid tapering;
• Transition to steroid-sparing strategies;
• Periodic reassessment of inflammatory activity; and
• Assessment of drug related toxicity and infectious complications.

Always look for inflection points—oxygen dependence, functional decline, transplant referral—recognizing that treatment goals evolve as disease progresses and patient priorities change. This might involve palliative care discussion.

Q. What are the practical challenges in managing adverse effects, and how do you minimize discontinuation?

The most common barrier to long-term therapy is toxicity rather than inefficacy. My strategy is proactive and to discuss the side effects well prior to starting therapy. Our pharmacists in ILD Center are proactive and counsel patients well and oversee titration and early dose modification. They also have a structured monitoring protocol and this approach, along with early follow-up, dramatically reduces unnecessary discontinuation.

Q. How do you manage heterogeneity, comorbidities, and evolving phenotypes over time?

I presume that up to 10% fibrotic ILD at presentation have pulmonary hypertension regardless of PFT or CT findings. I actively look for other comorbid conditions, such as obstructive sleep apnoea (OSA), gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) in those with shared risk factors. In general, I treat ILD as a longitudinal disease with evolving biology that might prompt us to revisit the diagnosis if there are new findings. I often do periodic re-phenotyping, aggressive management of comorbidities that amplify progression and early transplant referral, and early integration of palliative strategies for symptom control. In keeping with that principle, rather than seeking diagnostic purity, I focus on maintaining function and slowing decline with a focus on the patient at centre stage. It is always a partnership between the patient and the treatment team in the disease course that abets success.