A Research Guide for
IPF & Pulmonary Fibrosis

Several ILDs can look similar on CT scans, and misdiagnosis is common — studies show that up to 50% of patients initially diagnosed with IPF at community practices may have a different diagnosis when reviewed by an ILD-specialized multidisciplinary team. This matters because:

• Hypersensitivity pneumonitis: If the triggering exposure (birds, mold, hot tubs, feather bedding, certain chemicals) is identified and eliminated, the disease may stabilize or even partially improve. This opportunity is lost if the patient is simply labeled as having IPF.
• CTD-ILD: The underlying autoimmune disease may respond to immunosuppressive therapy (mycophenolate, rituximab, tocilizumab), which can slow or halt fibrosis progression in ways that antifibrotics alone cannot.
• Drug-induced ILD: Removing the offending medication may stop progression entirely.
• IPF: Immunosuppressive therapy (prednisone + azathioprine + NAC) was shown to be harmful in IPF by the PANTHER-IPF trial. Using the wrong diagnosis to justify these drugs can actively worsen outcomes.

This is why the multidisciplinary discussion (MDD) — a formal meeting of pulmonologist, radiologist, and pathologist reviewing your case together — is considered the gold standard for ILD diagnosis.

The GAP model (Gender, Age, Physiology) is a validated tool that estimates mortality risk in IPF. It uses four simple variables to assign a stage:

The GAP model was developed before antifibrotic therapy was widely available, so outcomes with modern treatment are likely somewhat better than these numbers suggest. It remains useful for understanding relative risk and guiding transplant referral timing. Your pulmonologist can calculate your GAP score and discuss what it means for your individual situation.

High-resolution computed tomography (HRCT) is the single most important diagnostic test for pulmonary fibrosis. Unlike a regular chest X-ray, HRCT provides detailed cross-sectional images of the lungs that can identify specific patterns of scarring. The scan is quick (a few minutes), painless, and does not require contrast dye for most ILD evaluations.

What the radiologist looks for:

• Honeycombing: Clusters of small, thick-walled cystic spaces, usually at the lung bases. This is the hallmark of the UIP pattern and strongly suggests IPF.
• Traction bronchiectasis: Airways stretched and distorted by surrounding scar tissue. Indicates significant fibrosis.
• Ground-glass opacity: Hazy areas that may represent inflammation, early fibrosis, or both.
• Reticulation: A net-like pattern of fine lines indicating thickened tissue between the air sacs.
• Distribution: Basal (lower lung) and subpleural (near the outer edges) predominance is characteristic of IPF/UIP. Upper-lobe predominance suggests other diagnoses (HP, sarcoidosis).

HRCT patterns in the 2022 ATS/ERS/JRS/ALAT IPF guidelines:

PFTs measure how well your lungs work. They are essential for diagnosis, tracking disease progression, and guiding treatment decisions. The two most important measurements in pulmonary fibrosis:

• Forced vital capacity (FVC): The total amount of air you can forcefully exhale after taking the deepest breath possible. In fibrosis, FVC is reduced because stiff lungs cannot expand fully. FVC decline over time is the primary measure of disease progression and the main outcome in clinical trials. A decline of ≥5% in 6–12 months is clinically meaningful and may indicate the need to start or change treatment.
• Diffusing capacity (DLCO): Measures how efficiently oxygen passes from the air sacs into the bloodstream. Often the earliest PFT abnormality in fibrosis, even when FVC is still normal. A decline of ≥10% is significant. Very low DLCO (≤35% predicted) indicates severe disease and is a trigger for transplant evaluation.

Other PFT findings in fibrosis:

• Total lung capacity (TLC) is reduced (restrictive pattern)
• FEV1/FVC ratio is normal or increased (unlike in COPD, where it is decreased)
• 6-minute walk distance (6MWD) and oxygen desaturation during the walk are functional measures that track exercise capacity and oxygen needs

PFTs should be performed at diagnosis and repeated every 3–6 months to track trends. A single measurement is less informative than the trajectory over time.

Blood tests help determine the cause of fibrosis and may provide prognostic information:

• Autoimmune panel: ANA, RF, anti-CCP, anti-Scl-70, anti-Jo-1, and other antibodies help identify or rule out connective tissue diseases as the underlying cause.
• Hypersensitivity pneumonitis panel: Precipitating antibodies (IgG) to specific antigens (bird proteins, mold species) can support an HP diagnosis, though false negatives and false positives are common.
• Complete blood count and metabolic panel: Baseline assessment for general health and to monitor for medication side effects.

Emerging biomarkers:

• KL-6 (Krebs von den Lungen-6): A mucin-like glycoprotein produced by damaged type II pneumocytes. Routinely used in Japan for diagnosis and monitoring. Elevated levels predict worse outcomes and may help identify patients who respond best to antifibrotic therapy. Gaining global adoption but not yet standard in the US.
• SP-D (surfactant protein D): Elevated in alveolar damage; correlates with disease activity.
• MMP-7 (matrix metalloproteinase 7): Elevated in IPF; associated with disease severity and mortality.
• TOLLIP rs3750920 genotype: A pharmacogenomic marker. Patients with the T/T genotype may benefit from N-acetylcysteine (NAC) supplementation, while those with C/C genotype may worsen with NAC. Testing is not yet routine but may become standard as precision medicine advances.
• Telomere length: Short telomeres are found in up to 25% of familial and some sporadic IPF cases. They predict faster progression and may influence transplant outcomes and immunosuppressive drug tolerance.

Lung biopsy is not always necessary for a pulmonary fibrosis diagnosis. When HRCT shows a definite UIP pattern in the right clinical context (age >60, male, smoking history, no obvious alternative cause), IPF can be diagnosed without biopsy. Biopsy is considered when:

• HRCT shows an indeterminate or non-UIP pattern, and the MDD team cannot confidently determine the diagnosis
• The patient is younger than expected for IPF (<50), raising concern for a different ILD
• The diagnosis will significantly change treatment decisions (e.g., distinguishing IPF from HP or NSIP, which may respond to immunosuppression)

Biopsy methods:

• Surgical lung biopsy (video-assisted thoracoscopic surgery, VATS): The traditional gold standard. A small incision between the ribs allows removal of a lung tissue sample. Provides the most tissue for analysis but carries procedural risk, especially in patients with advanced disease or pulmonary hypertension.
• Transbronchial cryobiopsy: A newer technique performed through a bronchoscope. A frozen probe is applied to the lung tissue, and a larger sample is obtained than with conventional transbronchial biopsy. Lower complication rates than surgical biopsy, though bleeding and pneumothorax can occur. Increasingly used as a less invasive alternative.

The risks and benefits of biopsy must be carefully weighed for each patient. In some cases, especially elderly patients with advanced disease, the risks of biopsy outweigh the potential diagnostic benefit. Discuss this thoroughly with your pulmonologist.

The MDD is a formal meeting where a pulmonologist (ILD specialist), a chest radiologist, and a pathologist (if biopsy was performed) review your case together to arrive at a consensus diagnosis. It is considered the gold standard for diagnosing interstitial lung diseases and is recommended by all major international guidelines.

Why it matters:

• Studies show that MDD changes the working diagnosis in 25–50% of cases compared to individual specialist assessment
• MDD increases diagnostic confidence, which guides more appropriate treatment
• It reduces the rate of unnecessary lung biopsies (sometimes the team agrees that imaging and clinical features are sufficient)
• It identifies cases where additional testing or a different workup is needed

If your diagnosis was made without an MDD — for example, by a general pulmonologist reviewing a CT scan alone — consider asking for referral to a center where MDD is routinely performed. Many academic medical centers and ILD-specialty centers offer this.

Nerandomilast is a first-in-class selective phosphodiesterase 4B (PDE4B) inhibitor developed by Boehringer Ingelheim. It represents the first new antifibrotic mechanism in over a decade and received two landmark FDA approvals:

• IPF approval: October 2025
• PPF approval: December 19, 2025 — making it one of only two drugs approved for PPF

How it works: By selectively inhibiting PDE4B, nerandomilast has a dual mechanism — both antifibrotic (reducing fibroblast activation and collagen production) and immunomodulatory (dampening inflammatory pathways that drive fibrosis). This is a fundamentally different approach from both nintedanib and pirfenidone.

Clinical trial evidence:

• FIBRONEER-IPF trial (NCT05321069): In approximately 1,200 IPF patients, nerandomilast 18 mg twice daily significantly reduced the annual rate of FVC decline compared to placebo (treatment difference approximately 69 mL at 52 weeks). An exploratory pooled analysis suggested a numerical mortality reduction, but the key secondary composite endpoint (acute exacerbation, respiratory hospitalization, or death) was not statistically significant. These findings should not be interpreted as a proven survival benefit.
• FIBRONEER-ILD trial (NCT05321082, PPF): 1,178 adults with progressive fibrosing ILDs (non-IPF) were treated for 52 weeks. Per the FDA approval summary, the 18 mg group experienced an average FVC decline of approximately −72 mL versus −151 mL for placebo — a clinically meaningful treatment difference of approximately 79 mL. Both the 9 mg and 18 mg doses showed statistically significant benefit.

Dosing: 18 mg taken orally twice daily (the recommended dose). Available in 9 mg and 18 mg tablets. Dose reduction to 9 mg BID is required when taken with strong CYP3A inhibitors (certain antibiotics and antifungals); moderate/strong CYP3A inducers should be avoided. When used with pirfenidone, the dose should remain at 18 mg BID (not reduced). Ask your pharmacist about potential drug interactions.

Side effects: The most common side effects include diarrhea (occurring in approximately 42% of patients on 18 mg in trials), nausea, depression, and fatigue. No head-to-head trial has compared GI tolerability directly to nintedanib or pirfenidone. Diarrhea rates may be higher when combined with nintedanib (up to 62% in some trial subgroups). Discontinuation rates due to adverse events were generally low.

Use as add-on therapy: Nerandomilast can be used as monotherapy OR as add-on therapy for patients already taking nintedanib or pirfenidone whose disease continues to progress. This is a significant advantage — it opens a combination approach that was not previously possible.

Nintedanib is a tyrosine kinase inhibitor that blocks multiple growth factor receptors involved in the fibrotic process (VEGFR, FGFR, PDGFR). FDA approved for IPF (2014) and for progressive fibrosing ILDs/PPF (based on the INBUILD trial).

Dosing: 150 mg taken orally twice daily with food.

Key trial evidence:

• INPULSIS-1 and INPULSIS-2 trials (IPF): Reduced annual FVC decline by approximately 50% compared to placebo.
• INBUILD trial (PPF): Demonstrated significant reduction in FVC decline in patients with progressive fibrosing ILDs of various causes. This was the trial that established the PPF treatment paradigm.
• SENSCIS trial: Showed benefit specifically in scleroderma-related ILD.

Side effects:

• Diarrhea: The most common side effect, occurring in approximately 62% of patients. Usually manageable with loperamide (Imodium), dietary modifications, and dose reduction. Severe in about 5% of patients.
• Liver toxicity: Liver function tests (ALT, AST, bilirubin) must be monitored before starting treatment, monthly for the first 3 months, and periodically thereafter. Significant elevations require dose reduction or discontinuation.
• Nausea, decreased appetite, weight loss: Common but usually mild to moderate.
• Bleeding risk: Nintedanib inhibits VEGFR and may increase bleeding risk. Use caution with anticoagulants. Full anticoagulation is a relative contraindication.

Practical tips: Take with food to reduce GI side effects. Stay well hydrated. Have loperamide on hand. Report persistent diarrhea (more than a few days) to your doctor rather than just tolerating it. Dose reduction to 100 mg twice daily is an option if side effects are intolerable at the full dose.

Pirfenidone’s exact mechanism of action is not fully understood, but it has antifibrotic, anti-inflammatory, and antioxidant properties. It was the first drug approved for IPF (originally in Japan and Europe; FDA approved in the US in 2014).

Dosing: Titrated over 14 days to the target dose of 801 mg (three 267 mg capsules) taken three times daily with food. The gradual dose escalation reduces GI side effects.

Key trial evidence:

• ASCEND trial: Reduced the proportion of patients with FVC decline ≥10% by approximately 50% compared to placebo over 52 weeks.
• CAPACITY trials: One of two trials met its primary endpoint for FVC decline reduction.
• Pooled analyses and real-world data: Consistent evidence of reduced FVC decline and possible mortality benefit.

Side effects:

• Gastrointestinal: Nausea, decreased appetite, and diarrhea are common. Usually mild to moderate and often improve after the first few months.
• Photosensitivity and skin rash: A distinctive side effect. Patients must avoid direct sun exposure, wear protective clothing, and use broad-spectrum SPF 50+ sunscreen daily. Sunburn can be severe.
• Liver toxicity: Less common than with nintedanib but requires liver function monitoring before treatment and periodically during therapy.
• Fatigue: Reported by some patients.

Practical tips: Always take with food (a full meal reduces nausea). Sunscreen is non-negotiable — apply before going outdoors, even on cloudy days. Start with the dose escalation schedule as prescribed. If GI symptoms are troublesome, taking the medication at the end of a meal rather than the beginning may help.

Real-world equivalence of nintedanib and pirfenidone: Multiple real-world comparative studies show that nintedanib and pirfenidone have equivalent efficacy in slowing FVC decline and comparable overall survival. The choice between them has historically been based on side effect profile and patient preference. Nerandomilast adds a third option with a novel mechanism and a different side-effect profile, plus the ability to be combined with either of the other two drugs.

Choosing the right antifibrotic depends on your specific situation:

• If you have IPF: All three drugs are approved options. Discuss side effect profiles and your lifestyle with your doctor. If you spend significant time outdoors, pirfenidone’s photosensitivity may be problematic. If you have liver disease or take anticoagulants, nintedanib requires extra caution.
• If you have PPF (non-IPF): Nintedanib and nerandomilast are FDA-approved for PPF. Pirfenidone is sometimes used off-label.
• If your disease progresses on one antifibrotic: Options include switching to a different antifibrotic, or adding nerandomilast as combination therapy. Disease progression on treatment is not “failure” — the drug may still be slowing decline even if it cannot halt it entirely.
• If side effects are intolerable: Switching to a different antifibrotic is standard practice. Each drug has a different side effect profile. Many patients who cannot tolerate one drug do well on another.

Never stop an antifibrotic without discussing it with your pulmonologist. Even temporary breaks can allow disease acceleration.

Pulmonary hypertension (PH) — elevated blood pressure in the arteries of the lungs — develops in 30–50% of patients with advanced pulmonary fibrosis. It significantly worsens exercise capacity, oxygen needs, and survival. Until recently, there were no approved treatments for PH associated with ILD.

Inhaled treprostinil (Tyvaso) changed this landscape. It is a prostacyclin analogue delivered via a handheld nebulizer, approved for PH associated with ILD (WHO Group 3 PH).

INCREASE trial: 326 patients with PH-ILD were treated for 16 weeks. Treprostinil improved 6-minute walk distance by 31 meters compared to placebo — a meaningful functional improvement. The FVC benefit was most pronounced in patients with IPF.

Practical considerations:

• Administered via the Tyvaso Inhalation System, 4 times daily (each session takes about 2–3 minutes)
• Dose is titrated up gradually to minimize side effects
• Common side effects: cough, headache, throat irritation, nausea, flushing
• A newer dry powder inhaler formulation (Tyvaso DPI) is available for convenience
• Not all PF patients need treprostinil — only those with confirmed PH, typically diagnosed by right heart catheterization or suggested by echocardiogram

New — inhaled treprostinil may be heading toward an IPF indication of its own. Until now, Tyvaso has been used in pulmonary fibrosis only when pulmonary hypertension is also present. The TETON Phase 3 program tested inhaled treprostinil in people with IPF regardless of whether they have pulmonary hypertension. Both pivotal trials met their main goal of slowing the decline in lung function (FVC) over 52 weeks: TETON-2 (597 patients, reported September 2025) and TETON-1 (598 patients, reported March 2026). The manufacturer (United Therapeutics) has said it plans to ask the FDA in 2026 to add IPF to the Tyvaso label. If approved, this would make inhaled treprostinil a treatment option for IPF itself — not only for IPF complicated by pulmonary hypertension. It is not yet FDA-approved for this use; ask your pulmonologist whether a TETON-based option may become available to you.

Gastroesophageal reflux disease (GERD) is extremely common in IPF patients — present in 50–90% by some estimates, though often without typical heartburn symptoms (“silent reflux”). Micro-aspiration of stomach acid into the lungs is hypothesized to worsen fibrosis, though this remains debated.

Current approach:

• Most ILD specialists treat GERD aggressively in IPF patients, typically with a proton pump inhibitor (PPI) such as omeprazole or pantoprazole
• Lifestyle modifications: elevate the head of the bed 6–8 inches, avoid eating within 3 hours of bedtime, limit acidic and fatty foods
• Some guidelines suggest surgical anti-reflux procedures (fundoplication) for patients with refractory GERD and progressive IPF, though evidence is limited
• The 2022 ATS/ERS/JRS/ALAT guideline made a conditional recommendation against using antacid therapy or antireflux surgery solely to treat IPF/respiratory outcomes; however, symptomatic GERD should still be treated under standard GI guidelines

Several treatments that were once commonly used or seemed reasonable have been proven ineffective or harmful in IPF. Knowing what to avoid is as important as knowing what works:

• Triple therapy (prednisone + azathioprine + NAC): The PANTHER-IPF trial was stopped early because this combination increased mortality, hospitalizations, and serious adverse events in IPF patients. This was a watershed moment in IPF management — immunosuppression is actively harmful in IPF.
• High-dose systemic corticosteroids (as maintenance therapy for IPF): Do not slow fibrosis and cause significant side effects (diabetes, osteoporosis, infections, weight gain). Short courses may be used for acute exacerbations, but long-term steroids are not appropriate for IPF.
• Warfarin: The ACE-IPF trial found warfarin was associated with increased mortality in IPF patients not requiring anticoagulation for other reasons.
• Ambrisentan: The ARTEMIS-IPF trial showed this endothelin receptor antagonist increased disease progression and hospitalizations in IPF.

Important note on immunosuppression: While immunosuppression is harmful in IPF, it may be beneficial and even necessary in other ILDs (CTD-ILD, HP, sarcoidosis). This is one of the many reasons correct diagnosis matters.

The first three months are the most critical window. Getting the diagnosis right and starting treatment early sets the trajectory for everything that follows. There is an understandable instinct to wait and watch — to see how the disease behaves before committing to a medication. Resist that instinct. Lung function lost before treatment starts cannot be recovered, and the fibrotic process does not pause while you decide.

• Confirm the diagnosis through multidisciplinary discussion (MDD). Your diagnosis should be reviewed jointly by a pulmonologist experienced in ILD, a chest radiologist, and, if a biopsy was done, a pathologist. A definite or probable UIP pattern on HRCT in the right clinical context (typically age over 50, male, smoking history, no identifiable cause) is sufficient for an IPF diagnosis without biopsy. If your diagnosis was made by a general pulmonologist without MDD review, a second opinion at a specialized ILD center is strongly advisable — misdiagnosis rates at non-specialist settings are significant, and the wrong diagnosis can mean the wrong treatment.
• Rule out treatable alternatives before accepting the IPF label. Hypersensitivity pneumonitis (HP), connective tissue disease-related ILD (CTD-ILD), and drug-induced ILD can all mimic IPF on imaging. These conditions have specific treatments that antifibrotics alone cannot provide — removing an exposure, treating an underlying autoimmune disease, or stopping an offending medication. Getting the diagnosis right matters enormously for your long-term outcome. A thorough environmental and occupational history, complete autoimmune blood panel, and a careful medication review are essential before the IPF label is confirmed.
• Start antifibrotic therapy now. All major international guidelines recommend starting an antifibrotic medication — nintedanib (Ofev), pirfenidone (Esbriet), or nerandomilast (Jascayd) — at the time of IPF diagnosis, not after documented decline. The drugs slow the rate of new scarring. Starting early protects the lung function you currently have.
• Establish baseline pulmonary function. FVC (forced vital capacity), DLCO (diffusing capacity), total lung capacity (TLC), and 6-minute walk test (6MWT) with pulse oximetry are your starting reference points. Every subsequent measurement will be compared to these baselines to determine whether your disease is progressing and at what rate.
• Refer to an ILD specialist center. Specialized ILD centers see far more cases than community practices and consistently achieve better diagnostic accuracy, provide access to clinical trials, and offer multidisciplinary care. Ask for referral to a center in the Pulmonary Fibrosis Foundation Care Center Network.
• Refer to a lung transplant center at diagnosis — not later. The American Thoracic Society recommends referral to a lung transplant center at the time of IPF diagnosis for all potentially eligible patients. Evaluation takes months; being referred early means an organ is more likely to be available when needed. This referral is not a commitment to transplant — it opens a door that takes time to walk through.
• Screen for GERD. Gastroesophageal reflux disease (acid reflux) is present in 50–90% of IPF patients, often without classic heartburn symptoms (“silent reflux”). Microaspiration of gastric contents may worsen lung injury and trigger exacerbations. Ask your doctor whether evaluation and treatment are appropriate.
• Baseline echocardiogram. Pulmonary hypertension (high blood pressure in the lung arteries) develops in 30–50% of IPF patients as the disease advances. An echocardiogram at or near diagnosis establishes baseline heart and pulmonary pressure data and allows early detection if PH develops.
• Assess oxygen saturation at rest and with exercise. Test your SpO&sub2; during the 6-minute walk. If saturation drops below 88% during exertion, supplemental oxygen during activity is appropriate now — even if you feel comfortable at rest. Inadequate oxygen worsens heart strain and fatigue.
• Vaccinations. Respiratory infections can trigger life-threatening acute exacerbations of IPF. Ensure you are current on influenza (annually), pneumococcal (PCV20 or PCV15+PPSV23 series), COVID-19 (including updated boosters), RSV (for adults 60+), and shingles (Shingrix for adults 50+).
• Advance care planning — begin the conversation early. Conversations about your future care wishes — mechanical ventilation, CPR, intensive care, and end-of-life preferences — are far more valuable when held calmly while you are well than in a crisis. Complete an advance directive and designate a healthcare proxy. In IPF, an acute exacerbation can occur with little warning and carries very high mortality; having your wishes documented and understood by your family and care team is a genuine act of self-care.
• Smoking cessation. If you currently smoke, stopping is the single most protective action available to you. Smoking accelerates fibrosis, reduces pirfenidone blood levels (by inducing the enzyme that breaks it down), and increases exacerbation risk. Your care team can provide cessation support including medication and counseling.

The first year establishes your response to treatment, reveals how quickly your disease is moving, and gives you time to build the habits and support systems that will matter throughout your journey.

• Repeat PFTs every 3–6 months. An FVC decline of ≥5% over 6–12 months, or ≥10% over 12 months, is clinically meaningful evidence of faster-than-average progression. A DLCO decline of ≥10% over 12 months is similarly significant. Trends matter more than individual readings. Bring a simple graph or table of your values to each appointment — your care team should have this, but having your own copy keeps you informed and engaged.
• Repeat 6-minute walk test every 3–6 months. Declining walk distance and worsening oxygen desaturation during the walk are independent predictors of mortality and key drivers of transplant timing discussions. If you start needing oxygen during the walk that you did not need before, report this to your doctor promptly.
• Antifibrotic side-effect management. Diarrhea on nintedanib should be managed proactively: take the drug with food, use loperamide (Imodium) at the first sign of loose stools, stay well hydrated, and if symptoms are persistent, ask about dose reduction to 100 mg twice daily. Sun sensitivity on pirfenidone requires daily SPF 50+ sunscreen on all exposed skin and protective clothing outdoors — even on cloudy days. GI upset on any of the three antifibrotics usually improves over the first weeks. The critical message: call your doctor before stopping any antifibrotic due to side effects. There is almost always a management strategy — dose adjustment, schedule change, or supportive medication — that allows you to continue. Stopping without a plan allows the disease to accelerate.
• Blood tests per monitoring schedule. Both nintedanib and pirfenidone require monthly liver function test monitoring for the first 3 months, then quarterly. Nerandomilast requires monitoring per current prescribing information. Keep these appointments; liver toxicity is manageable when caught early and dangerous when missed.
• Start pulmonary rehabilitation. A supervised exercise and education program, ideally started within the first year, significantly improves exercise capacity, reduces breathlessness, and enhances quality of life. Ask your pulmonologist for a referral at your next visit. Most programs run 6–12 weeks with sessions 2–3 times per week and are covered by Medicare and most private insurers.
• Annual lung cancer screening. IPF patients have 3–5 times higher lung cancer risk than the general population, driven by shared risk factors (smoking, age, male sex) and by the lung remodeling that fibrosis causes. Annual low-dose CT chest screening is appropriate. The CT performed for ILD monitoring may partially overlap with this, but ensure your doctor is explicitly reviewing for early lung nodules.
• Annual echocardiogram. Screen for developing pulmonary hypertension, especially if your breathlessness seems to be worsening faster than your PFT numbers would predict, if you notice new leg swelling, or if your exercise tolerance is declining more rapidly than expected.
• Sleep assessment. Obstructive sleep apnea affects 50–80% of IPF patients and is frequently unrecognized. Signs include snoring, waking unrefreshed, pauses in breathing during sleep (observed by a partner), and excessive daytime sleepiness. Untreated sleep apnea worsens nocturnal oxygen desaturation, cardiovascular strain, and daytime fatigue. Ask about a sleep study if you have these symptoms.
• Mental health check-in. Anxiety and depression affect 25–50% of IPF patients and significantly impair quality of life, reduce treatment adherence, and worsen physical function. These are medical conditions, not signs of weakness. Ask your doctor to screen you at each visit using a validated questionnaire. Effective treatment — psychotherapy, medication, or both — is available.
• Check in with the transplant evaluation. Ensure the evaluation is progressing. The full process typically takes 3–6 months and involves cardiac testing, extensive lab work, imaging, pulmonary function testing, psychosocial assessment, and nutritional review. If you have not heard from the transplant team after being referred, follow up proactively.

For many patients on antifibrotic therapy, a period of slower progression is achievable — sometimes years of meaningful stability. Long-term management focuses on maintaining gains, adapting to gradual change, and planning ahead so that when major decisions are needed, you are ready.

• Stay on antifibrotics — do not stop without guidance. Even when you feel stable, your medication is actively protecting you. Temporary breaks for surgery or severe illness should be as brief as possible and always coordinated with your pulmonologist, with a clear plan to resume. Antifibrotics should be continued through disease progression — they slow the slope even when they cannot halt it. Stopping allows acceleration.
• Consider combination therapy if progressing. If your FVC continues to decline on a single antifibrotic, adding nerandomilast (Jascayd) as a second antifibrotic with a different mechanism is now an evidence-based option based on the FIBRONEER trial data. Ask your pulmonologist whether combination therapy is appropriate for you. This is a significant advance over what was available just a few years ago.
• Reassess transplant listing urgency. If FVC falls below 70% predicted, or DLCO below 40% predicted, or if you have required supplemental oxygen, or if you have been hospitalized for respiratory deterioration — contact your transplant team immediately. These are triggers for active listing, not merely evaluation. Do not wait for your next scheduled appointment if these thresholds are crossed.
• Explore clinical trials. The IPF research pipeline is more active than ever. If you are on a stable antifibrotic and have been on it for 6+ months, you may be eligible for add-on trials of novel agents. Ask at every visit what trials are open at your center or nearby. Trial participation gives you access to potentially beneficial treatments and close monitoring by an expert team.
• Consider genetic testing if you have family history. If two or more close relatives have had interstitial lung disease, or if you developed IPF at younger than typical age (under 60), ask about referral for genetic counseling and testing for familial pulmonary fibrosis genes (particularly TERT, TERC, and MUC5B). This information matters for family members’ surveillance and occasionally for treatment decisions.
• Optimize oxygen therapy as needs evolve. As the disease advances, oxygen requirements change. Ensure your prescription accurately reflects your needs at rest, during exertion, and during sleep (which may require separate flow rates). Work with a DME provider experienced in IPF to ensure you have equipment capable of delivering adequate flow rates during activity, including a portable concentrator for travel.
• Palliative care referral when symptoms burden quality of life. Palliative care is not the same as hospice. A palliative care specialist can help manage breathlessness, chronic cough, anxiety, and other symptoms at any stage of disease — alongside, not instead of, your antifibrotic therapy and transplant evaluation. Ask for a referral when symptoms begin to significantly affect your daily life; there is no reason to wait until the final stages.
• Revisit advance care planning at least annually. As disease progresses, your wishes may evolve. Review your advance directive and have an explicit conversation with your pulmonologist about your preferences regarding mechanical ventilation. In IPF patients with advanced disease or acute exacerbation, intubation and mechanical ventilation is associated with very high mortality (>90% in non-transplant candidates) and is often not consistent with quality-of-life goals. Having documented wishes ensures your family and care team can honor them without guessing in a crisis.

A typical PR program runs 6–12 weeks, with sessions 2–3 times per week. Each session lasts 1–2 hours and includes:

• Supervised exercise: Aerobic training (treadmill, stationary bike, walking) and strength training tailored to your current fitness and oxygen levels. Exercise intensity is gradually increased as tolerated. Supplemental oxygen is provided during exercise if needed.
• Education: Understanding your disease, medication management, breathing techniques, energy conservation, nutrition, and when to seek help.
• Breathing strategies: Pursed-lip breathing, diaphragmatic breathing, and positioning techniques that reduce the sensation of breathlessness.
• Psychosocial support: Group interaction with other patients, anxiety and depression management, and connection to community resources.

What PR achieves:

• Improved 6-minute walk distance (exercise capacity)
• Reduced breathlessness during daily activities
• Improved quality of life scores
• Reduced anxiety and depression
• Better ability to perform daily tasks independently
• Improved confidence in managing the disease

PR does not reverse lung scarring or improve lung function test numbers. What it does is train your body to use the lung function you have more efficiently and improve your cardiovascular fitness, so you can do more with less lung reserve.

Ask your pulmonologist for a referral to a pulmonary rehabilitation program. Most programs are covered by Medicare and private insurance for patients with documented lung disease. Barriers to access include limited program availability in rural areas, transportation challenges, and long wait lists.

Alternatives if traditional PR is not accessible:

• Home-based PR programs: Some centers offer supervised virtual or telephone-based programs with home exercise guidance. The COVID-19 pandemic accelerated the development of telehealth PR.
• Self-directed exercise: If no formal program is available, work with your pulmonologist and a physical therapist to develop a safe home exercise plan. Walking is the simplest and most effective form of aerobic exercise for PF patients.
• Maintenance programs: After completing formal PR, maintenance exercise programs (often community-based) help preserve the gains.

As pulmonary fibrosis progresses, blood oxygen levels may drop — first during exertion, then during sleep, and eventually at rest. Supplemental oxygen does not slow fibrosis, but it relieves breathlessness, improves exercise tolerance, supports organ function, and may reduce the strain on the heart caused by pulmonary hypertension.

When oxygen is needed:

• Oxygen saturation (SpO2) consistently below 88% at rest, or below 88% during exertion (determined by a 6-minute walk test with oximetry)
• Some patients need oxygen only during exercise; others need it during sleep and exercise; eventually some need it continuously
• Your pulmonologist determines the flow rate (liters per minute) needed to maintain SpO2 at or above 88–90%

Types of oxygen delivery systems:

• Portable oxygen concentrators (POC): Battery-powered devices that extract oxygen from room air. Lightweight and suitable for travel. Pulse-dose delivery (delivers oxygen only during inhalation) is energy-efficient but may not provide enough oxygen for all patients during exertion.
• Home oxygen concentrators: Larger stationary units that provide continuous-flow oxygen. Used at home with long tubing to allow movement around the house.
• Compressed gas cylinders: Backup tanks for when concentrators are unavailable (power outages, travel). Come in various sizes from small portable tanks to large home tanks.
• Liquid oxygen: Stores large amounts of oxygen in a compact liquid form. Used less commonly now due to the prevalence of concentrators.

Practical tips:

• Work with a durable medical equipment (DME) provider experienced with ILD patients — oxygen needs for pulmonary fibrosis are often higher than for COPD
• Request a portable unit that can deliver high enough flow rates for your exercise needs
• Airplane travel requires FAA-approved portable concentrators — plan ahead and notify the airline
• Use a pulse oximeter at home to monitor your oxygen levels

Chronic cough affects 70–85% of IPF patients and is one of the most distressing and undertreated symptoms. It is typically dry, persistent, and can be triggered by talking, laughing, eating, or changes in temperature. It disrupts sleep, causes exhaustion, leads to social embarrassment and isolation, and can trigger urinary incontinence.

Treatment options (in order of typical approach):

• Treat contributing factors: GERD (acid reflux), post-nasal drip, and medication side effects (ACE inhibitors cause cough in 5–20% of users — switch to an ARB) should be addressed first.
• Speech therapy/physiotherapy: Speech and language therapists can teach cough suppression techniques, breathing pattern modification, and laryngeal control exercises. This is an underused but effective approach.
• Low-dose opioids: Low-dose morphine or codeine can suppress the cough reflex. Studies show benefit in chronic refractory cough. Side effects include constipation, drowsiness, and nausea. Start with the lowest dose.
• Gabapentin: Originally an anti-seizure medication, gabapentin can reduce chronic cough by acting on neural pathways. Typically started at a low dose and titrated up. Side effects include drowsiness and dizziness.
• Thalidomide: Has shown benefit in small trials for IPF cough, but significant side effects (peripheral neuropathy, teratogenicity, sedation) limit its use to refractory cases under specialist supervision.

Over-the-counter cough suppressants (dextromethorphan, guaifenesin) are generally ineffective for the cough of pulmonary fibrosis. Do not waste money on cough syrups without discussing with your doctor.

Pulmonary fibrosis affects far more than just breathing. The psychological and quality-of-life impact is profound:

• Sleep disruption: Cough, oxygen desaturation during sleep, and anxiety can all disturb sleep. Overnight oximetry may reveal the need for nocturnal oxygen. Screen for obstructive sleep apnea (OSA), which is common and treatable.
• Fatigue: Present in the majority of PF patients and often more debilitating than breathlessness. Multifactorial — related to low oxygen levels, disrupted sleep, depression, medication side effects, and deconditioning. Pulmonary rehabilitation and energy conservation strategies help.
• Depression and anxiety: Affect 25–50% of PF patients and are associated with worse outcomes, reduced treatment adherence, and poorer quality of life. These are medical conditions, not character flaws, and effective treatments exist. Do not hesitate to discuss your emotional health with your pulmonologist or primary care doctor.
• Social isolation: Breathlessness, oxygen equipment, and fatigue can limit social activities. Support groups (in-person and online), pulmonary rehab, and occupational therapy for adaptive strategies can all help maintain social connections.

Ask for help. Mental health treatment — whether counseling, medication, or both — can genuinely improve quality of life and should be considered a core part of PF management, not an optional add-on.

Respiratory infections are particularly dangerous for people with pulmonary fibrosis. Reduced lung reserve means that even a mild infection can cause significant deterioration, and infections may trigger acute exacerbations. Prevention is critical:

• Influenza vaccine: Annually, every fall. High-dose formulation recommended for adults ≥65.
• Pneumococcal vaccines: PCV20 (Prevnar 20) or PCV15 followed by PPSV23, per current CDC recommendations. Discuss with your doctor if not yet vaccinated.
• COVID-19 vaccines: Stay up to date with current boosters. Immunocompromised patients (including those on immunosuppression for CTD-ILD) may benefit from additional doses.
• RSV vaccine: FDA approved for adults ≥60; discuss with your doctor given your increased vulnerability to respiratory infections.
• Shingles vaccine (Shingrix): Recommended for adults ≥50. Shingles can be severe in immunocompromised patients.

Beyond vaccination: practice good hand hygiene, avoid close contact with sick individuals, wear a mask in crowded indoor spaces during respiratory illness season, and seek prompt medical attention for any respiratory infection symptoms.

Why nutrition becomes difficult:

• Increased caloric demand: The effort of breathing through stiff, fibrotic lungs increases resting energy expenditure. Patients with significant lung restriction may burn 10–15% more calories than healthy individuals at rest, simply to breathe. If caloric intake does not keep pace, muscle wasting occurs.
• Reduced appetite: Breathlessness, fatigue, nausea from antifibrotic medications, and depression all suppress appetite. Many IPF patients eat less than they need without realizing it.
• Eating is physically demanding: Chewing, swallowing, and digesting food requires effort, and for patients with severe breathlessness, eating a full meal can be exhausting. Shortness of breath after meals is common.
• GERD and dietary restrictions: Acid reflux management (avoiding large meals, acidic foods, eating late at night) can further limit what and when patients eat comfortably.
• Antifibrotic side effects: Nausea (especially with pirfenidone), diarrhea (especially with nintedanib), and reduced appetite affect all three antifibrotics and can significantly reduce nutritional intake if not managed.

Practical nutritional strategies:

• Eat smaller, more frequent meals. Five or six small meals or snacks throughout the day are easier to manage than three large meals. Large meals cause the stomach to press against the diaphragm, which can worsen breathlessness.
• Choose nutrient-dense foods. When appetite is limited, every bite counts. Prioritize foods that provide protein and calories efficiently: eggs, Greek yogurt, nut butters, avocado, full-fat dairy, beans, and lean meats.
• Eat your main meal when you are least fatigued. For most people, energy is highest in the morning. Eating a larger, higher-calorie meal early in the day may be easier than forcing yourself to eat at dinner when you are exhausted.
• Rest before eating if breathlessness is severe. Taking oxygen (if prescribed), resting for 20–30 minutes before a meal, and eating in an upright sitting position can all reduce breathlessness during eating.
• Oral nutritional supplements. High-calorie liquid supplements (Ensure, Boost, or prescription medical nutrition supplements) can bridge caloric gaps when solid food intake is insufficient. Discuss options with your doctor or a registered dietitian.
• Address antifibrotic-related nausea actively. Taking antifibrotics at the end of a full meal (rather than with just a few bites of food) often reduces nausea significantly. Anti-nausea medications can be prescribed if needed.
• Protein intake. Aim for adequate protein to maintain muscle mass, which is essential for exercise tolerance and functional independence. A rough guideline for patients with lung disease is approximately 1.0–1.5 grams of protein per kilogram of body weight daily. A registered dietitian can help calculate your specific target.
• Hydration. Adequate hydration helps thin airway secretions and reduce cough. Aim for at least 6–8 cups of fluid daily unless your doctor has recommended fluid restriction for other reasons (such as heart failure).

Energy conservation techniques help you accomplish more of what matters most while using less oxygen and causing less breathlessness. These strategies are taught in pulmonary rehabilitation but can be applied immediately:

• Plan your day around your energy peaks. Most people with pulmonary fibrosis have better energy at certain times of day. Schedule important activities, exercise, and demanding tasks during these windows. Rest during low-energy periods.
• Sit to do tasks whenever possible. Standing and working simultaneously uses significantly more oxygen than sitting. Install a stool in the kitchen for cooking, use a shower chair, and sit while dressing. These adaptations reduce breathlessness during daily tasks without compromising independence.
• Use the right tools. Long-handled grabbers, sock aids, elevated toilet seats, and other adaptive devices reduce the bending, reaching, and straining that increase oxygen demand. An occupational therapist can assess your home and recommend specific adaptations.
• Break tasks into steps with rest periods. Instead of cleaning the entire kitchen in one session, clean one section, rest, then continue. Instead of climbing stairs all at once, pause at a landing. This “pacing” approach allows you to accomplish tasks that would otherwise be impossible.
• Organize your environment to minimize exertion. Keep frequently used items within easy reach at waist height. Store cleaning supplies on each floor so you don’t have to carry them up stairs. Set up a bedside station with medications, phone charger, and tissues so nighttime needs are met without getting up.
• Use breathing techniques during exertion. Pursed-lip breathing during effortful activities (going up stairs, dressing, carrying) slows the respiratory rate and improves oxygen exchange. Exhale during the effort (when lifting, pushing, or pulling) rather than holding your breath.

Telomere-Related Genes (TERT, TERC, RTEL1, PARN)

Telomeres are protective caps on the ends of chromosomes that shorten with each cell division. In pulmonary fibrosis, mutations in genes that maintain telomere length are the most common genetic cause of both familial and some sporadic cases. The key genes:

• TERT (telomerase reverse transcriptase) and TERC (telomerase RNA component): Together, these account for the majority of familial pulmonary fibrosis cases. Mutations cause abnormally short telomeres, which impair the ability of lung cells to repair themselves. TERT and TERC mutations are associated with a clinical syndrome called “telomeropathy” that can also include premature graying of hair, liver disease (cirrhosis), and bone marrow failure.
• RTEL1 and PARN: Less common telomere pathway genes found in familial ILD cases. RTEL1 mutations in particular are associated with an aggressive fibrotic phenotype.
• Clinical implication of short telomeres: Telomere length can be measured in blood cells. Patients with very short telomeres (below the 10th percentile for age) have worse prognosis, higher risk after lung transplant, and may tolerate immunosuppressive medications poorly (risk of bone marrow suppression). Some programs check telomere length routinely in patients being considered for transplant.

Surfactant Protein Genes (SFTPC, SFTPB)

Surfactant proteins are produced by type II alveolar epithelial cells and help keep the lung air sacs open and functioning. Mutations in SFTPC and, more rarely, SFTPB can cause familial ILD, often presenting at a younger age than typical sporadic IPF. These mutations are more commonly associated with children who develop ILD, but adults with SFTPC mutations can develop fibrosis in their 30s–50s.

MUC5B Promoter Variant — The Most Common Genetic Risk Factor for Sporadic IPF

The most common genetic risk factor for IPF is not a mutation in a gene but a change near a gene — specifically, a common variant in the promoter region of MUC5B (the gene encoding the mucin protein MUC5B). This variant, called rs35705950 (the “T allele”), is found in approximately 30–38% of IPF patients compared to about 9% of the general population. Having this variant significantly increases the risk of developing IPF.

An important reassurance about MUC5B: Despite increasing the risk of developing IPF, the MUC5B T allele is actually associated with somewhat better survival after diagnosis compared to those without it. This is a counterintuitive finding — the same variant that makes you more likely to get the disease appears to be associated with a slightly slower course once diagnosed. Do not interpret a positive MUC5B test as meaning your prognosis is worse than average; the opposite appears to be the case.

TOLLIP Genetic Variant

A variant in the TOLLIP gene (rs3750920) has been shown in a pharmacogenomic study (a post-hoc analysis of the PANTHER-IPF trial) to be associated with differential response to N-acetylcysteine (NAC). Patients with the T/T genotype showed better survival with NAC, while those with the C/C genotype showed worse outcomes. This finding has not yet led to routine clinical testing but illustrates the emerging concept of precision medicine in IPF — where genetic profile may guide specific treatment choices in the future.

Genetic testing for pulmonary fibrosis is not yet standard for all patients but is increasingly useful in specific situations:

• Familial pulmonary fibrosis. If you have two or more relatives with interstitial lung disease of any kind, genetic counseling and testing are appropriate. A genetics specialist can order a gene panel covering telomere pathway genes, surfactant proteins, and other ILD-associated genes, and can interpret the results in the context of your family history.
• Younger-than-typical age at diagnosis. IPF typically presents in adults over 60. If you or a family member developed ILD at a notably younger age (under 55–60), genetic testing may identify an underlying hereditary cause that explains the early onset.
• Features suggesting telomeropathy. If you or your relatives have premature graying (before age 30), liver disease, blood count abnormalities, or other features of telomere dysfunction, this is a signal to pursue testing for telomere gene mutations and telomere length measurement.
• Pre-transplant evaluation. Many transplant programs now routinely measure telomere length as part of the evaluation, because very short telomeres can affect post-transplant outcomes and tolerance of anti-rejection medications.
• If your doctor suspects a hereditary component. Unexpected features in your clinical presentation, unusual disease course, or a thorough review of your family history may prompt your pulmonologist to recommend genetic evaluation.

Genetic counseling before testing. Genetic testing for lung fibrosis genes ideally involves consultation with a genetic counselor beforehand. A counselor can explain what the tests can and cannot tell you, discuss implications for your relatives, help you think through whether you want to know the results, and ensure you understand what a positive or negative result means — and what it does not mean.

If you carry a gene mutation associated with familial pulmonary fibrosis (particularly a TERT, TERC, or SFTPC mutation), your first-degree relatives (parents, siblings, children) have a 50% chance of carrying the same mutation. However, carrying the mutation does not guarantee they will develop lung fibrosis — penetrance (the chance that a mutation actually causes disease in a carrier) is variable, and many mutation carriers never develop clinical fibrosis.

Surveillance for at-risk relatives: If your relatives carry the same mutation, or if your family has a strong history of ILD, it is reasonable to discuss with a pulmonologist whether periodic monitoring is warranted. This might include periodic pulmonary function testing (FVC, DLCO) and potentially periodic HRCT imaging to detect early fibrosis before it causes symptoms. Very early detection might allow earlier antifibrotic treatment, though this hypothesis is still being studied in clinical trials.

Lifestyle advice for at-risk relatives: Smoking cessation is the most evidence-supported preventive measure for anyone at genetic risk of pulmonary fibrosis. Smoking dramatically increases the risk of developing manifest ILD in genetically susceptible individuals. Minimizing exposure to organic dust, metal dust, and other known fibrosis triggers is also advisable.

The American Thoracic Society and international guidelines recommend transplant referral at the time of IPF diagnosis. The evaluation and listing process takes months — sometimes over a year — and organs may not become available immediately. Being evaluated early ensures you are listed while you are still well enough to undergo and recover from surgery.

Specific triggers for referral or listing:

• IPF diagnosis (regardless of severity — refer early)
• Definite UIP pattern on HRCT (indicates the most aggressive fibrotic pattern)
• FVC decline ≥5% over 6 months despite antifibrotic therapy
• DLCO <40% predicted
• Development of pulmonary hypertension
• Desaturation below 88% during 6-minute walk test
• Need for supplemental oxygen
• Hospitalization for respiratory decline or acute exacerbation
• Pneumothorax (collapsed lung — indicates advanced structural disease)

General transplant candidacy requirements:

• Age: most programs accept candidates up to age 65–70, though policies vary
• Adequate cardiac, renal, and hepatic function
• Ability to participate in post-transplant rehabilitation
• Adequate social support and medication adherence capacity
• No active infection, recent malignancy, or substance use disorder
• BMI within acceptable range (typically 18–32)

Evaluation: A comprehensive multi-day assessment at a transplant center, including cardiac testing, lab work, imaging, psychosocial evaluation, nutritional assessment, and rehabilitation assessment. The transplant team determines if you are a candidate and, if so, lists you on the national organ waitlist.

Bilateral transplant is now standard for IPF patients, replacing single-lung transplant as the preferred approach. Bilateral transplant offers better long-term survival, better lung function, and avoidance of complications from native (scarred) lung hyperinflation.

Waitlist and allocation: The Composite Allocation Score (CAS, which replaced the former Lung Allocation Score in March 2023) prioritizes patients based on medical urgency and expected post-transplant benefit. IPF patients tend to receive higher CAS scores due to the progressive nature of the disease, often resulting in shorter wait times than other diagnoses.

Ex vivo lung perfusion (EVLP): A transformative technology where donor lungs that might otherwise be rejected are placed on a machine that perfuses and ventilates them outside the body, allowing assessment and reconditioning. EVLP is significantly expanding the donor pool and reducing wait times at centers that use it.

Post-transplant: Lifelong immunosuppressive medications to prevent organ rejection (typically tacrolimus, mycophenolate, and prednisone). Regular bronchoscopies and lung function tests to monitor for rejection. Risk of infection due to immunosuppression. Chronic lung allograft dysfunction (CLAD) remains the major long-term challenge.

Outcomes: Median post-transplant survival continues to improve, with many bilateral lung transplant recipients surviving well beyond 5 years. Individual outcomes depend on age, overall health, the transplant center’s experience, and post-transplant care adherence.

Key facts:

• Annual incidence: 5–15% of IPF patients per year
• In-hospital mortality: >50%
• 30-day mortality: approximately 36%
• 90-day mortality: approximately 57%
• 46% of all IPF deaths are preceded by an acute exacerbation

What happens: A wave of new lung inflammation (diffuse alveolar damage) is superimposed on the existing fibrosis, causing rapid deterioration in gas exchange and severe respiratory distress. On HRCT, new widespread ground-glass opacities appear over the background fibrotic pattern.

Triggers: In many cases, no trigger is identified (hence “idiopathic”). Known triggers include respiratory infections, aspiration, surgical procedures, and mechanical ventilation. Some exacerbations may be triggered by micro-aspiration or air pollution.

Seek emergency care immediately if you experience:

• Sudden, significant worsening of breathlessness over a period of days to a few weeks — noticeably worse than your baseline
• New inability to perform activities you could do recently
• Oxygen saturation dropping well below your usual levels despite using your prescribed oxygen flow rate
• New or worsening cough, with or without fever
• Severe fatigue or confusion

What to bring to the emergency department:

• Your medical summary card (diagnosis, medications, oxygen prescription, pulmonologist contact)
• A list of your current medications and dosages
• Your most recent PFT results and HRCT report (have these in your phone or health binder)
• Contact information for your pulmonologist so the ED team can consult them

Treatment is largely supportive, and outcomes remain poor despite best available care:

• High-dose pulse corticosteroids: Methylprednisolone 1,000 mg intravenously daily for 3 days is the standard initial treatment, followed by a tapering dose of oral prednisone. Evidence for this approach is limited to observational studies, but it remains standard practice.
• Supportive care: High-flow oxygen or non-invasive ventilation (BiPAP), treatment of any identified infection, nutritional support, and DVT prophylaxis.
• Continue antifibrotic therapy: Antifibrotic medications should generally be continued through an exacerbation if the patient can tolerate oral medications.
• Avoid invasive mechanical ventilation when possible: In IPF patients with acute exacerbations, invasive mechanical ventilation is associated with very high mortality (>90% in many series). Decisions about ventilation should be guided by advance directives and realistic discussions about prognosis.

Emerging approaches:

• Baricitinib: A JAK inhibitor already approved for rheumatoid arthritis and COVID-19; a 2025 retrospective study suggested potential benefit in AE-IPF. Further research is needed.
• Rituximab + plasmapheresis + IVIg: Being investigated for severe autoimmune-mediated exacerbations, particularly in cases with features suggesting an autoimmune component.

Breathlessness is the most disabling symptom of pulmonary fibrosis. It limits activity, disrupts sleep, causes anxiety, and profoundly affects quality of life. Several interventions can help:

• Low-dose opioids. Small doses of oral morphine (typically 2.5–5 mg every 4 hours, or a slow-release formulation) are among the most effective treatments for chronic, refractory breathlessness in pulmonary fibrosis — and among the most underused. Multiple controlled studies show benefit. When used at appropriate low doses under medical supervision, opioids for breathlessness do not hasten death. They work by reducing the sensation of air hunger and lowering the anxiety that accompanies difficult breathing. If breathlessness is significantly limiting your quality of life and other measures have not been sufficient, ask specifically about low-dose morphine. Many patients are not offered it because of an outdated belief that opioids are only for cancer pain or the terminal phase.
• A fan directed at the face. This is one of the simplest, cheapest, and most evidence-supported interventions for breathlessness that most patients have never heard of. Cool air movement across the cheek and upper lip stimulates receptors that reduce the perception of dyspnea through a nervous system pathway. A small handheld fan or a desktop fan directed at the lower half of the face during episodes of breathlessness can provide meaningful relief. It works even when oxygen levels are adequate.
• Supplemental oxygen (when indicated). Oxygen relieves breathlessness caused by low blood oxygen, but has less effect when oxygen levels are normal. If your oxygen levels are maintained but breathlessness remains severe, a fan or opioids may be more helpful than increasing oxygen flow.
• Anxiolytics for anxiety-related breathlessness. Breathlessness and anxiety form a vicious cycle: breathlessness causes anxiety, and anxiety worsens the sensation of breathlessness. Low-dose lorazepam (0.5–1 mg) or other short-acting benzodiazepines can interrupt this cycle during acute episodes of breathlessness triggered or amplified by anxiety. They are not a substitute for addressing the underlying cause but can be genuinely helpful for acute episodes. Use under medical supervision, especially given IPF patients’ tendency toward oxygen desaturation.
• Positioning. Many people with pulmonary fibrosis breathe more comfortably in an upright or forward-leaning position. Sleeping with the head of the bed elevated (using a wedge pillow or elevating the bed frame) or sitting upright rather than lying flat during episodes of breathlessness can provide measurable relief.
• Breathing techniques. Pursed-lip breathing (breathing in through the nose and out through pursed lips, as if blowing out a candle) and diaphragmatic breathing techniques, learned in pulmonary rehabilitation, slow the respiratory rate and reduce the sensation of breathlessness. These can be used anywhere, anytime, without equipment.

Chronic cough affects 70–85% of IPF patients. It is typically dry, persistent, and triggered by talking, laughing, eating, temperature changes, or exercise. It disrupts sleep, causes social embarrassment, leads to exhaustion, and can trigger incontinence. It is one of the most undertreated symptoms in IPF — ask specifically for help with cough management if it is affecting your life.

• Step 1: Treat contributing causes. GERD (acid reflux) contributes to cough in many IPF patients and should be treated. ACE inhibitor blood pressure medications cause cough in 5–20% of users — switching to an ARB (e.g., losartan) eliminates this cause. Post-nasal drip should be addressed.
• Step 2: Gabapentin. Gabapentin (originally an anti-seizure medication) is one of the best-supported treatments for chronic refractory cough, including IPF cough. It works on neural pathways that drive the hypersensitive cough reflex. Typical starting doses are 100–300 mg twice daily, titrating upward. Side effects include drowsiness and dizziness, which usually improve with time. This is an off-label use but is widely employed and supported by evidence in chronic refractory cough.
• Step 3: Low-dose opioids for cough. Low-dose codeine or morphine can suppress the cough reflex and is appropriate when gabapentin is insufficient. Use under medical supervision.
• Step 4: Speech therapy. A speech and language therapist trained in cough management can teach laryngeal control exercises, breathing strategies, and cough suppression techniques. This is an underused but genuinely effective approach.
• Step 5: Thalidomide. Has shown benefit in small trials for IPF cough, but significant potential side effects (nerve damage, blood clots, birth defects) limit its use to refractory cases under specialist supervision with strict risk management.
• What does not work: Over-the-counter cough syrups (dextromethorphan, guaifenesin) are generally ineffective for the cough of pulmonary fibrosis. Cough drops may temporarily soothe the throat but do not address the underlying neurological hypersensitivity driving the cough reflex in IPF.

Hospice is appropriate when the focus of care shifts from slowing disease progression to maximizing comfort and quality of life in the final phase of illness. It does not mean giving up or that death is imminent; it means choosing expert symptom management, dignity, and support over more aggressive interventions that no longer serve the patient’s goals.

When to consider hospice:

• Continuous supplemental oxygen dependence (day and night)
• Lung transplant is no longer an option (either ruled out or the patient has chosen not to pursue it)
• Breathlessness is dominating quality of life despite optimal medical management
• Frequent hospitalizations that are not improving the underlying situation
• The patient has expressed that comfort and time at home matter more than further disease-modifying treatment

What hospice provides: Hospice is not a place but a philosophy of care that can be delivered at home. A hospice team typically includes nurses, aides, social workers, chaplains, and physicians who specialize in comfort care. They focus on symptom management (breathlessness, cough, anxiety, pain), caregiver support, and ensuring the patient’s wishes are honored in their final weeks and months.

Hospice and antifibrotics: Hospice does not automatically mean stopping antifibrotic medications. Patients who wish to continue antifibrotics and whose hospice program and insurer allow it may do so. Discuss this with your hospice team. The decision about whether to continue antifibrotics in the context of hospice is personal and should reflect your own values and goals.

Initiate the conversation early. Asking about hospice should happen when you are stable enough to have a meaningful conversation about it, not in an ICU during a crisis. Your pulmonologist, palliative care specialist, or primary care doctor can start this discussion. Many people find that learning about hospice early — and knowing it is available as an option — provides comfort and reduces fear about the future.

• Bexotegrast (PLN-74809): An integrin inhibitor that blocks key molecular pathways driving fibrosis. Early Phase 2 data showed reduced FVC decline, but development was halted in 2025 after the BEACON-IPF Phase 2b/3 trial (NCT06097260) was discontinued (March 2025) due to an unfavorable risk-benefit profile. This is a reminder that promising early results do not always translate to safe and effective therapy.
• Saracatinib: A Src kinase inhibitor being studied in the Phase 1b/2a STOP-IPF trial (NCT04598919).
• Admilparant (BMS-986278): An oral medicine that blocks the LPAR1 receptor, part of a fibrosis-driving pathway. It is the first drug of its kind to reach Phase 3 testing in IPF and progressive lung fibrosis (the ALOF-IPF and ALOF-PPF trials).
• BI 765423 (anti-IL-11): An antibody against interleukin-11, one of the most overactive signals in IPF scar-forming cells. It entered Phase 2 testing in 2026 — the first treatment to target this particular pathway.
• AI-assisted HRCT analysis: Artificial intelligence applied to HRCT scans may enable earlier detection of fibrosis progression, more precise quantification of disease extent, and better prediction of response to therapy — moving toward truly personalized treatment.
• Genomic-guided therapy: Identifying genetic variants (TOLLIP, MUC5B, telomere genes) that predict treatment response, enabling precision medicine approaches rather than one-size-fits-all treatment.

Therapies that have failed in late-stage trials:

• Pamrevlumab (anti-CTGF): The ZEPHYRUS-1 Phase 3 trial missed its primary endpoint. Development was terminated.
• Zinpentraxin alfa (pentraxin-2/PRM-151): Phase 3 trial failed to meet its primary endpoint despite promising Phase 2 data.

These failures, while disappointing, provide important scientific information that guides the development of future therapies. The IPF research community learns from every trial.

• ClinicalTrials.gov: The comprehensive US database of clinical trials. Search for “idiopathic pulmonary fibrosis” or “progressive pulmonary fibrosis” and filter by location, status (recruiting), and phase.
• Your ILD specialist: Academic ILD centers are often trial sites. Ask your pulmonologist what trials are available at their institution or nearby.
• Pulmonary Fibrosis Foundation Clinical Trial Finder: A patient-friendly search tool at pulmonaryfibrosis.org.
• Manufacturer registries: Boehringer Ingelheim (maker of nintedanib and nerandomilast) and other pharmaceutical companies maintain trial registries.

What to know about clinical trials:

• You may receive the experimental drug or a placebo (sugar pill), depending on the trial design
• You will be closely monitored with frequent visits, which means more attention to your care
• Many trials allow you to continue your current antifibrotic therapy
• You can withdraw from a trial at any time
• Participation is voluntary and should never be pressured
• Travel and visit costs are often partially or fully covered by the trial sponsor

Advance care planning is not giving up — it is ensuring your wishes are known and respected at every stage of your disease. Given the unpredictable course of IPF (including the possibility of sudden acute exacerbations), these conversations should happen early, when you are feeling well and can think clearly.

Key components:

• Advance directive: A legal document specifying your preferences for medical care if you cannot speak for yourself (life support, mechanical ventilation, CPR, feeding tubes).
• Healthcare proxy/power of attorney: Designate someone to make medical decisions on your behalf if you are unable to.
• Goals of care conversations: Discuss with your pulmonologist what matters most to you — quality of life vs. quantity, comfort vs. aggressive treatment, home vs. hospital for end-of-life care.
• POLST/MOLST form: A portable medical order that translates your advance directive into actionable medical instructions for emergency personnel.

Palliative care is not the same as hospice. Palliative care focuses on symptom management, quality of life, and support — and can be provided alongside curative or disease-modifying treatments at any stage of illness. It does not mean you are “giving up.” Specialist palliative care teams can help manage breathlessness, cough, anxiety, pain, and other symptoms that affect daily life. Ask your pulmonologist about a palliative care referral at any point when symptoms are affecting your quality of life.

• Pulmonary Fibrosis Foundation (PFF): pulmonaryfibrosis.org — The leading US patient advocacy organization. Offers a PFF Care Center Network of 85+ specialized ILD programs, support groups, educational programs, a clinical trial finder, and a PFF Patient Communication Center for personalized support. Their PFF Help Line (844-TalkPFF / 844-825-5733) connects you with trained staff who can answer questions and provide resources.
• American Lung Association: lung.org — Patient education, local support groups, Better Breathers Clubs, and advocacy for lung disease research funding. Their helpline (1-800-LUNGUSA) provides support and resource referrals.
• Three Lakes Foundation: threelakesfoundation.org — Funds early-stage IPF research and provides patient education materials focused on pulmonary fibrosis specifically.
• Caring for Pulmonary Fibrosis (CFPF): cfpf.org — Patient education, online support community, and educational video library.
• PF Warriors: An online patient community with peer support, shared experiences, and practical tips for daily living with PF.

Antifibrotic medications, oxygen equipment, and frequent medical visits create significant financial burden. Help is available:

• Boehringer Ingelheim patient assistance: The manufacturer of nintedanib (Ofev) and nerandomilast (Jascayd) offers copay assistance and free drug programs for eligible patients. Contact 1-844-276-8262 or visit their patient support website.
• Genentech (Roche) patient assistance: The manufacturer of pirfenidone (Esbriet) offers the Esbriet Access Solutions program with copay support, free drug programs, and insurance navigation assistance.
• HealthWell Foundation: Provides copay assistance for qualifying patients with pulmonary fibrosis.
• Patient Access Network (PAN) Foundation: Offers financial assistance for eligible patients with chronic and life-threatening diseases including pulmonary fibrosis.
• Medicare and Medicaid: Both cover antifibrotic medications, oxygen therapy, and pulmonary rehabilitation. Medicare Part D copays can still be substantial — the assistance programs above can help with the gap.
• Social Security Disability: IPF may qualify for Social Security disability benefits, particularly with compassionate allowance expedited processing for advanced cases.

Connecting with others who understand what you are going through can be profoundly comforting and practically helpful:

• PFF Support Groups: In-person and virtual support groups facilitated by trained leaders. Find one at pulmonaryfibrosis.org or call the PFF Patient Communication Center.
• Inspire PF Community: A moderated online discussion forum where patients and caregivers share experiences, tips, and support.
• Facebook groups: Search for “Pulmonary Fibrosis” or “IPF Support” — multiple active groups exist. Exercise caution with medical advice from non-professional sources.
• PF Patient podcasts and YouTube channels: Several patient advocates produce regular content about living with PF, treatment updates, and practical advice.

• University of Utah Health — Interstitial Lung Disease Clinic: A multidisciplinary ILD program with pulmonologists specializing in fibrotic lung disease, chest radiologists, and pathologists who participate in multidisciplinary discussions (MDD). Offers antifibrotic therapy management, clinical trial access, and coordination with the transplant program. Part of the PFF Care Center Network. Phone: 801-581-2121 (main); ILD/pulmonary referrals through University of Utah Health system.
• University of Utah Lung Transplant Program: The region’s lung transplant center, providing evaluation, listing, surgery, and post-transplant care. Early referral from ILD clinic to transplant team is facilitated by their co-location. Phone: 801-581-2121.
• Intermountain Health Pulmonary Services: Multiple locations across the Wasatch Front offering pulmonary function testing, pulmonary rehabilitation programs, and general pulmonology. Can initiate workup and refer to specialized ILD centers as needed. Phone: 801-442-2000 (main).
• Intermountain Health Pulmonary Rehabilitation Programs: Structured outpatient PR programs available at several Intermountain locations, including Murray, Salt Lake City, and surrounding communities. Phone: 801-442-2000.

• Home oxygen providers: Multiple durable medical equipment (DME) companies serve the Utah market, including Apria Healthcare, Lincare, and local providers. Your pulmonologist’s office can recommend providers experienced with ILD patients who need high-flow oxygen systems.
• Home health agencies: For patients needing home nursing support, respiratory therapy, or palliative care at home, several agencies serve the Salt Lake City metro and surrounding areas.
• Utah altitude considerations: Utah’s higher elevation (Salt Lake City is at approximately 4,200 feet) means lower atmospheric oxygen pressure than at sea level. PF patients in Utah may need supplemental oxygen at lower levels of disease severity than patients at sea level. Discuss altitude effects with your pulmonologist, especially if you travel between different elevations within the state (ski resorts, southern Utah).

• PFF Support Groups: The Pulmonary Fibrosis Foundation facilitates support groups in the Salt Lake City area. Check pulmonaryfibrosis.org for current schedules, or call the PFF Patient Communication Center at 844-TalkPFF (844-825-5733).
• American Lung Association Better Breathers Club: Local chapters meet regularly and welcome patients with all chronic lung diseases. Visit lung.org to find a chapter near you.
• University of Utah ILD patient support: Ask your ILD team about patient education sessions, support groups, and caregiver resources affiliated with the program.

These search terms can help you find current, evidence-based information about pulmonary fibrosis:

• nerandomilast Jascayd FDA approval 2025
• FIBRONEER-IPF trial results
• FIBRONEER-ILD progressive pulmonary fibrosis
• ATS ERS JRS ALAT IPF guidelines 2022
• progressive pulmonary fibrosis criteria PPF
• nintedanib vs pirfenidone real-world comparison
• pulmonary fibrosis lung transplant referral timing
• acute exacerbation IPF management
• bexotegrast IPF Phase 2 trial
• KL-6 biomarker pulmonary fibrosis
• Pulmonary Fibrosis Foundation Care Center Network

• Nintedanib (Ofev): FDA-approved for IPF (2014), systemic sclerosis-associated ILD (2019), and chronic fibrosing ILDs with a progressive phenotype (2020).
• Pirfenidone (Esbriet): FDA-approved for IPF (2014). Not approved for non-IPF fibrosing ILDs in the US (off-label use occurs).
• Nerandomilast (Jascayd): FDA-approved for IPF (2025), the third antifibrotic to receive FDA approval. Approved as monotherapy or as add-on to existing antifibrotic therapy.
• Inhaled treprostinil (Tyvaso): FDA-approved for pulmonary hypertension associated with ILD (PH-ILD, Group 3), including ILD secondary to IPF. Not an antifibrotic but addresses a major comorbidity.

• Nintedanib (Ofev): EMA-approved for IPF (2015) and for other chronic fibrosing ILDs with a progressive phenotype (2020). Widely available across EU member states.
• Pirfenidone (Esbriet): EMA-approved for mild-to-moderate IPF (2011) — notably approved in Europe three years before the US. It was the first antifibrotic approved anywhere in the world outside Japan.
• Nerandomilast: Under regulatory review by the EMA as of 2025. European patients do not yet have access outside of clinical trials or named-patient programs.

Access and reimbursement vary by individual EU country. In some nations, antifibrotic prescribing is restricted to specialist ILD centers.

• Nintedanib: NICE-recommended for IPF with FVC 50–80% predicted (Technology Appraisal TA379). Available through NHS ILD specialist centres.
• Pirfenidone: NICE-recommended for IPF with FVC 50–80% predicted (Technology Appraisal TA504). Managed through NHS specialist centres with FVC monitoring requirements.
• Nerandomilast: Not yet approved or recommended in the UK as of 2025. MHRA review pending.

In the UK, NICE restricts antifibrotic initiation to patients with FVC between 50% and 80% predicted, which is more restrictive than US prescribing. Patients outside this range may not receive NHS-funded antifibrotic therapy. The British Thoracic Society (BTS) ILD guidelines provide additional clinical guidance for UK practice.

• Pirfenidone: First approved for IPF in Japan in 2008 — the first antifibrotic approved for IPF anywhere in the world. Japan has the longest real-world experience with antifibrotic therapy.
• Nintedanib: PMDA-approved for IPF (2015) and for progressive fibrosing ILDs.
• Nerandomilast: Developed by Boehringer Ingelheim with significant clinical trial participation in Japan. Regulatory submission to PMDA has been made.

Japan has been a leader in IPF research and was the first country to adopt antifibrotic therapy. The Japanese Respiratory Society (JRS) is a co-author of the international ATS/ERS/JRS/ALAT IPF guidelines.

• Nintedanib: Health Canada-approved for IPF (2015) and chronic fibrosing ILDs with a progressive phenotype. Provincial formulary coverage varies.
• Pirfenidone: Health Canada-approved for IPF (2015). Formulary listing and patient access programs differ by province and territory.
• Nerandomilast: Not yet approved in Canada as of 2025. Health Canada review anticipated.

The Canadian Thoracic Society provides clinical practice guidelines for IPF management. The Canadian Pulmonary Fibrosis Foundation (CPFF) advocates for equitable provincial access to antifibrotic therapies.

• Nintedanib: TGA-approved for IPF and listed on the Pharmaceutical Benefits Scheme (PBS) for subsidized access.
• Pirfenidone: TGA-approved for IPF and PBS-listed.
• Nerandomilast: Not yet approved in Australia as of 2025.

Australia has a well-organized ILD clinical network, and the Lung Foundation Australia provides patient support, education, and advocacy. PBS subsidization makes antifibrotic medications financially accessible for eligible patients.

• FVC restrictions: NICE (UK) restricts antifibrotic initiation to patients with FVC 50–80% predicted. The US FDA labels have no FVC-based restrictions, allowing treatment at any disease severity. This means some patients in the UK may not qualify for NHS-funded treatment while the same patients in the US would receive therapy.
• Conditional use of NAC: The 2022 ATS/ERS/JRS/ALAT guidelines give a conditional recommendation against N-acetylcysteine (NAC) in IPF. However, some centres (particularly in Japan) continue to use NAC as part of management, especially in the context of emerging pharmacogenomic data suggesting benefit in TOLLIP T/T genotype patients.
• Antacid therapy: The 2022 ATS/ERS/JRS/ALAT guideline gives a conditional recommendation against using antacid medication (PPIs or H2 blockers) or anti-reflux surgery to improve respiratory outcomes in IPF (based on WRAP-IPF and other data). Treating symptomatic acid reflux for the usual gastrointestinal reasons is unaffected; discuss with your team.
• Combination antifibrotic therapy: The FDA approval of nerandomilast as add-on therapy establishes combination antifibrotic treatment as a standard option in the US. This approach is not yet available in most other countries pending nerandomilast regulatory review.
• Lung transplant access: Wait times, allocation systems, and age cut-offs vary significantly between countries. The US uses the Composite Allocation Score (CAS), which replaced the Lung Allocation Score (LAS) in March 2023, while other countries use different allocation criteria. Patients near border regions should explore transplant eligibility in both countries if applicable.

• Why does fibrosis begin in some people and not others with the same risk factors? Many people smoke, work in dusty environments, or carry the MUC5B risk variant without developing IPF. We do not fully understand what triggers the initial fibrotic cascade in susceptible individuals. Multiple hypotheses exist (repeated microscopic lung injury, abnormal wound healing, epigenetic changes, viral triggers), but the initiating event remains unclear.
• Whether earlier antifibrotic initiation — before symptoms develop — improves outcomes. Clinical trials are currently investigating whether starting antifibrotic therapy in people with subclinical or early radiographic IPF (before measurable lung function decline) produces better long-term outcomes than waiting for symptoms. Current guidelines recommend starting at diagnosis, but “diagnosis” typically occurs after some degree of lung function has already been lost. Earlier intervention could potentially preserve more lung function.
• Whether combination antifibrotic therapy is superior to monotherapy. The FIBRONEER trials showed nerandomilast benefits patients with or without background antifibrotic therapy. Whether adding nerandomilast produces meaningfully better outcomes than continuing a single antifibrotic, and for which patients the benefit is largest, is still being studied in real-world and trial settings.
• The role of the lung microbiome. The lungs have their own community of microorganisms (the lung microbiome), which appears to be altered in IPF patients compared to healthy individuals. Whether these microbiome changes drive fibrosis, result from it, or are both — and whether modifying the lung microbiome could slow disease progression — is an active area of research.
• Whether anti-acid therapy truly modifies IPF disease course. The relationship between gastroesophageal reflux, microaspiration, and IPF progression is plausible but unproven in randomized trials. The PANTHER-IPF trial showed that triple immunosuppressive therapy was harmful, but the anti-acid component has not been definitively tested in a large controlled trial. The 2022 ATS/ERS guideline moved from a conditional recommendation for anti-acid therapy to a conditional recommendation against using it solely to modify IPF respiratory outcomes — reflecting the weakness of the evidence in either direction.
• Why some patients have a slow, gradual decline while others have rapid deterioration. IPF is notoriously unpredictable at the individual level. We can calculate population-level probabilities but cannot reliably tell any given patient how fast their disease will progress. Biomarkers (KL-6, telomere length, MUC5B genotype, MMP-7, SP-D) provide some prognostic information but are not precise enough to individualize predictions. Developing better predictors of individual disease trajectory is an active research priority.
• Whether any therapy can reverse or halt (not merely slow) fibrosis. All currently approved antifibrotics slow the rate of FVC decline but do not reverse existing scarring. Achieving true disease stabilization or partial reversal of fibrosis is the long-term goal. Some preclinical research suggests it may be possible, but no therapy has yet demonstrated this in human clinical trials.
• The optimal management of acute exacerbations. High-dose pulse corticosteroids are the standard treatment for AE-IPF despite very weak evidence of benefit — no randomized controlled trial has compared them to placebo until very recently. The first such trial (NCT05674994) is currently underway. Better treatments for acute exacerbations remain an urgent unmet need.

6-minute walk test (6MWT)

A standardized test of exercise capacity in which you walk as far as possible in 6 minutes on a flat surface. The distance walked and, crucially, how much your oxygen saturation drops during the test are both used to assess disease severity, track progression over time, and determine oxygen requirements during activity. Desaturation below 88% during the 6MWT is a significant finding that may indicate the need for supplemental oxygen during exercise and is a trigger for transplant evaluation consideration.

Acute exacerbation of IPF (AE-IPF)

A sudden, clinically significant worsening of respiratory symptoms over days to weeks that is not explained by heart failure, pulmonary embolism, or an identifiable infection. Acute exacerbations carry in-hospital mortality exceeding 50% and require emergency hospitalization. New widespread ground-glass opacities appear on HRCT superimposed over the background fibrotic pattern. Annual incidence is 5–15% of IPF patients per year.

Advance directive

A legal document that specifies your preferences for medical care in the event you become unable to speak for yourself. In IPF, advance directives typically address wishes regarding mechanical ventilation, CPR, feeding tubes, and intensive care. Given the unpredictable course of IPF and the risk of acute exacerbations, completing an advance directive early is strongly recommended.

Alveoli

The tiny air sacs at the ends of the breathing tubes in the lungs, where oxygen passes into the bloodstream and carbon dioxide passes out. In pulmonary fibrosis, the walls of the alveoli become thickened and scarred, impairing this gas exchange. There are approximately 300–500 million alveoli in healthy adult lungs.

Antifibrotic

A medication that slows or inhibits the formation of scar tissue (fibrosis). Three antifibrotic drugs are currently FDA-approved for IPF: nintedanib (Ofev), pirfenidone (Esbriet), and nerandomilast (Jascayd). Antifibrotics do not reverse existing scarring but significantly slow the rate of new scar formation — by approximately 50% compared to untreated disease. They represent the most important pharmacological advance in IPF care.

Bilateral lung transplant

A surgical procedure in which both of a patient's diseased lungs are removed and replaced with two healthy donor lungs. Bilateral transplant is now the preferred approach for IPF over single-lung transplant, offering better long-term survival and function because it avoids complications from the remaining native (scarred) lung. It requires matching by blood type and body size and involves a waiting period on a national organ waitlist.

Biomarker

A measurable substance in the body (typically in blood, urine, or tissue) that indicates disease presence, severity, or response to treatment. In IPF, biomarkers being studied include KL-6, SP-D, MMP-7, and telomere length. Some biomarkers can help predict disease trajectory or response to specific treatments.

Combined pulmonary fibrosis and emphysema (CPFE)

A syndrome in which upper-lobe emphysema (air trapping and overinflation from smoking) coexists with lower-lobe pulmonary fibrosis. The two conditions partially offset each other's effects on lung volumes, meaning spirometry (FVC, TLC) may look deceptively normal while DLCO (gas transfer) is severely impaired. CPFE patients have a particularly high rate of pulmonary hypertension and a worse prognosis than IPF alone. DLCO and echocardiography are more reliable monitoring tools than FVC in this setting.

Connective tissue disease-related ILD (CTD-ILD)

Interstitial lung disease that occurs in association with an underlying autoimmune condition such as rheumatoid arthritis, scleroderma (systemic sclerosis), myositis, Sjögren syndrome, or mixed connective tissue disease. CTD-ILD is distinct from IPF in that treating the underlying autoimmune disease may help control the lung inflammation and fibrosis. Some patients with CTD-ILD also qualify for antifibrotic therapy if their lung disease develops a progressive phenotype (PPF).

CYP1A2

A liver enzyme that metabolizes (breaks down) pirfenidone. CYP1A2 is induced (activated) by cigarette smoking, meaning smokers metabolize pirfenidone faster and may have lower drug levels in their blood. This is one important reason why smoking cessation is strongly encouraged in IPF patients taking pirfenidone. Certain medications (particularly fluvoxamine, an antidepressant) powerfully inhibit CYP1A2, causing dangerously high pirfenidone levels; this combination is contraindicated.

Dyspnea

The medical term for breathlessness or difficulty breathing. In pulmonary fibrosis, dyspnea initially occurs only with exertion (climbing stairs, walking fast), but progressively occurs with less activity and eventually at rest as the disease advances. Dyspnea is the most disabling symptom of IPF and significantly impairs quality of life. It can be measured using validated questionnaires and treated with a combination of supplemental oxygen, pulmonary rehabilitation, opioids, and other symptom management strategies.

DLCO (diffusing capacity of the lungs for carbon monoxide)

A pulmonary function test that measures how efficiently oxygen passes from the air sacs (alveoli) into the bloodstream. In pulmonary fibrosis, DLCO is reduced because scar tissue thickens the membrane between air and blood. DLCO decline is often the earliest detectable sign of fibrosis and a key indicator of disease severity. A DLCO at or below 35% predicted indicates severe disease and is a trigger for transplant evaluation consideration.

Esbriet

The brand name for pirfenidone, manufactured by Genentech (a member of the Roche Group). Esbriet was FDA-approved for IPF in October 2014. It is taken as 801 mg (three 267 mg capsules) three times daily with food. A generic pirfenidone has also become available in some markets.

Ex vivo lung perfusion (EVLP)

A technology in which donor lungs that might otherwise be rejected for transplant are placed on a specialized machine outside the body that perfuses and ventilates them, allowing assessment and sometimes reconditioning before transplant. EVLP is significantly expanding the pool of usable donor lungs and reducing wait times for lung transplant candidates.

Familial pulmonary fibrosis

Pulmonary fibrosis that occurs in two or more first-degree relatives within the same family. Familial pulmonary fibrosis accounts for approximately 5–10% of all IPF cases. It is most commonly caused by mutations in genes involved in telomere maintenance (TERT, TERC, RTEL1) or surfactant protein function (SFTPC, SFTPB). Family members of patients with familial pulmonary fibrosis may benefit from genetic counseling.

FVC (forced vital capacity)

The total volume of air a person can forcefully exhale after taking the deepest possible breath. FVC is reduced in pulmonary fibrosis because stiff, scarred lungs cannot expand fully. FVC expressed as a percentage of the expected value for the patient's age, sex, and height (“% predicted”) is used to classify disease severity and track progression. An FVC decline of ≥5% within 6–12 months is clinically meaningful evidence of faster progression.

GERD (gastroesophageal reflux disease)

A condition in which stomach acid and contents flow back into the esophagus and sometimes into the lungs (microaspiration). GERD is extremely common in IPF — present in 50–90% of patients, often without classic heartburn symptoms. Chronic microaspiration may worsen lung injury. Treatment typically involves proton pump inhibitors (PPIs), dietary modifications, and positioning changes.

Ground-glass opacity (GGO)

A term used in radiology to describe a hazy, semi-transparent area on a CT scan of the lungs that does not obscure the underlying blood vessels and airway walls. Ground-glass opacities indicate partial filling or thickening of the air sacs and can represent inflammation, early fibrosis, or fluid. In acute exacerbation of IPF, new bilateral ground-glass opacities are a key diagnostic finding, appearing superimposed on the chronic fibrotic pattern.

Honeycombing

A pattern on HRCT or chest X-ray in which the lung contains clusters of small, thick-walled cystic spaces resembling a honeycomb. Honeycombing indicates advanced fibrosis and irreversible structural destruction of the lung architecture. It is the hallmark radiological feature of the UIP pattern and strongly suggests IPF when present in the lower lungs near the outer edges (basal, subpleural location). Once honeycombing is present, the lung tissue it occupies cannot return to normal.

HRCT (high-resolution computed tomography)

A specialized CT scan that produces detailed cross-sectional images of the lungs at thin-slice resolution (typically 1–1.5 mm slices). HRCT is the single most important diagnostic test for pulmonary fibrosis, identifying specific patterns of scarring that distinguish IPF from other interstitial lung diseases. It is performed quickly, is painless, and usually does not require contrast dye for ILD evaluation.

ILD (interstitial lung disease)

An umbrella term for over 200 conditions that cause inflammation and/or scarring of the lung tissue (the interstitium — the tissue framework surrounding and supporting the air sacs and airways). Pulmonary fibrosis is one type of ILD. Other ILDs include hypersensitivity pneumonitis, sarcoidosis, and connective tissue disease-related lung disease. Not all ILDs cause fibrosis; some are primarily inflammatory and may respond to anti-inflammatory treatment.

IPF (idiopathic pulmonary fibrosis)

The most common and most aggressive form of pulmonary fibrosis, in which the cause of lung scarring is unknown (“idiopathic”). IPF typically affects adults over 50, is more common in men, and has a median survival of 3–5 years without treatment. It follows the UIP pattern on imaging and is relentlessly progressive. Three medications (nintedanib, pirfenidone, nerandomilast) are approved to slow its progression. IPF is the leading indication for lung transplant worldwide.

Jascayd

The brand name for nerandomilast, a first-in-class PDE4B inhibitor manufactured by Boehringer Ingelheim. Approved by the FDA for IPF in October 2025 and for PPF in December 2025. It represents the first new antifibrotic mechanism approved in over a decade. Jascayd can be used alone or added to nintedanib or pirfenidone for patients progressing on their existing therapy.

KL-6 (Krebs von den Lungen-6)

A mucin-like protein produced by damaged type II alveolar epithelial cells and bronchiolar epithelial cells. KL-6 levels in the blood are elevated in pulmonary fibrosis and correlate with disease severity and mortality risk. KL-6 testing is used routinely for IPF diagnosis and monitoring in Japan and is gaining adoption in other countries. It can be used alongside FVC and DLCO to track disease progression and potentially to monitor treatment response.

MDD (multidisciplinary discussion)

A formal meeting in which a pulmonologist experienced in ILD, a thoracic radiologist, and (when biopsy has been performed) a lung pathologist review a patient's clinical history, imaging, and pathology together to arrive at a consensus diagnosis. MDD is the gold standard diagnostic approach for ILD and is recommended by all major international guidelines. Studies show that MDD changes the working diagnosis in 25–50% of cases compared to single-specialist assessment.

MUC5B

A gene encoding a mucin protein important for airway defense. A common genetic variant near the MUC5B gene (rs35705950, called the “T allele”) is the strongest genetic risk factor for sporadic IPF, found in 30–38% of IPF patients compared to about 9% of the general population. Paradoxically, carrying this risk variant is associated with somewhat better survival after IPF diagnosis, not worse prognosis.

NSIP (nonspecific interstitial pneumonia)

A type of interstitial lung disease characterized by diffuse, relatively uniform inflammation and/or fibrosis of the lung tissue, with a basal-predominant but often more symmetric distribution than UIP. NSIP is the most common ILD pattern in connective tissue disease-related ILD. Unlike UIP, NSIP often has areas of ground-glass opacity and tends to spare the area immediately beneath the pleura (subpleural sparing). Distinguishing NSIP from UIP is important because NSIP may respond to immunosuppressive therapy, while UIP (IPF) does not.

Ofev

The brand name for nintedanib, manufactured by Boehringer Ingelheim. FDA-approved for IPF (2014), for systemic sclerosis-associated ILD (2019), and for other progressive fibrosing ILDs (2020). Taken as 150 mg twice daily with food. The most common side effect is diarrhea, managed with loperamide, dietary modifications, and if necessary dose reduction to 100 mg twice daily.

Palliative care

Specialized medical care focused on symptom relief, quality of life, and support for patients with serious illness and their families. In pulmonary fibrosis, palliative care can begin at diagnosis alongside disease-modifying treatment (antifibrotics, transplant evaluation) and focuses on managing breathlessness, cough, anxiety, pain, and the emotional burden of the disease. Palliative care is not the same as hospice — it is appropriate at any stage of illness.

PDE4B (phosphodiesterase 4B)

An enzyme involved in regulating inflammatory and fibrotic signaling pathways in the lungs. Nerandomilast (Jascayd) selectively inhibits PDE4B, reducing both the inflammatory signals that activate scar-forming cells and the fibrotic activity of those cells. Inhibiting PDE4B represents a mechanistically distinct approach from nintedanib (which blocks growth factor receptors) and pirfenidone (whose exact mechanism is less defined).

PDGFR (platelet-derived growth factor receptor)

One of three growth factor receptors blocked by nintedanib (alongside VEGFR and FGFR). PDGFs are signaling proteins that stimulate fibroblast proliferation and differentiation, driving scar tissue formation. By blocking PDGFR, nintedanib interrupts one of the key molecular pathways that drives fibrosis in IPF.

PFT (pulmonary function test)

A battery of tests measuring how well the lungs work. In pulmonary fibrosis, the most important PFTs are FVC (forced vital capacity), DLCO (diffusing capacity), TLC (total lung capacity), and the 6-minute walk test with oximetry. PFTs are performed at diagnosis to establish baselines and repeated every 3–6 months to track disease progression and guide treatment decisions.

Photosensitivity

Increased sensitivity of the skin to ultraviolet light, leading to sunburns, rashes, or skin discoloration with normal sun exposure. Photosensitivity is a common side effect of pirfenidone (Esbriet), affecting approximately 12% of patients. It is managed with daily SPF 50+ broad-spectrum sunscreen applied to all exposed skin, protective clothing, and avoiding direct sun during peak UV hours (10 AM–4 PM). The photosensitivity risk is not present with nintedanib or nerandomilast.

PPF (progressive pulmonary fibrosis)

A clinical phenotype (not a separate diagnosis) describing patients with a non-IPF fibrosing lung disease whose fibrosis is getting progressively worse despite appropriate management of the underlying condition. PPF is defined by the presence of at least two of three criteria within the past year: worsening respiratory symptoms, physiological progression (FVC decline ≥5% or DLCO decline ≥10%), and radiological progression on HRCT. Nintedanib (INBUILD trial) and nerandomilast (FIBRONEER-ILD trial) are both approved for PPF.

Pulmonary hypertension (PH)

Elevated blood pressure in the pulmonary arteries (the blood vessels that carry blood through the lungs for oxygenation). In pulmonary fibrosis, PH develops as fibrosis destroys the lung blood vessels, forcing the right side of the heart to work harder. PH significantly worsens breathlessness, reduces exercise capacity, and is associated with worse outcomes. In IPF patients with PH, inhaled treprostinil (Tyvaso) is the only FDA-approved therapy. PH is diagnosed definitively by right heart catheterization and screened for by echocardiogram.

Pulmonary rehabilitation

A structured, supervised program of exercise training, education, and psychosocial support designed for patients with chronic lung disease. Programs typically run 6–12 weeks with sessions 2–3 times per week. Pulmonary rehabilitation does not reverse lung scarring but significantly improves exercise capacity, reduces breathlessness during daily activities, and enhances quality of life. Most programs are covered by Medicare and private insurance.

Reticulation

A network of fine lines visible on HRCT of the lungs, caused by thickening of the tissue between the air sacs and airways (the interstitium). Reticulation indicates fibrosis or inflammation of the lung interstitium and is one of the key radiological features of pulmonary fibrosis. It typically has a peripheral (outer edge) and basal (lower lobe) distribution in IPF.

SpO2 (oxygen saturation)

The percentage of hemoglobin in the blood that is carrying oxygen, measured non-invasively by a pulse oximeter (a device clipped to the fingertip). Normal SpO2 at sea level is 95–100%. In pulmonary fibrosis, SpO2 may be normal at rest but drop during exercise. An SpO2 consistently below 88% at rest or below 88% during the 6-minute walk test is a threshold for supplemental oxygen prescription.

Supplemental oxygen

Additional oxygen delivered through a nasal cannula or mask to maintain adequate blood oxygen levels. In pulmonary fibrosis, oxygen needs evolve: initially only during exertion, then during sleep, and eventually at rest. Supplemental oxygen relieves breathlessness during activity, supports heart function by reducing pulmonary vasoconstriction, and improves sleep quality. It does not slow fibrosis or extend overall survival but significantly improves functional capacity and quality of life.

Telomere

A protective cap on the end of each chromosome, often compared to the plastic tip on a shoelace. Telomeres shorten with each cell division, and very short telomeres signal cells to stop dividing. In pulmonary fibrosis, mutations in genes responsible for maintaining telomere length (particularly TERT and TERC) are the most common known genetic causes of familial IPF, and short telomeres in general are associated with a more aggressive disease course and worse outcomes after lung transplant.

Telomeropathy

A clinical syndrome caused by mutations in genes that maintain telomere length (telomerase pathway genes: TERT, TERC, RTEL1, PARN, and others). Features of telomeropathy include pulmonary fibrosis, premature graying of hair (before age 30), liver cirrhosis, bone marrow failure (low blood counts), and other manifestations of premature cellular aging. Not all patients with telomere gene mutations develop all features; the syndrome exists on a spectrum.

TERT / TERC

TERT (telomerase reverse transcriptase) and TERC (telomerase RNA component) are the two main components of telomerase, the enzyme that maintains telomere length. Together, mutations in TERT and TERC are the most common genetic cause of familial pulmonary fibrosis. TERT mutations are particularly common. Patients with TERT or TERC mutations tend to develop pulmonary fibrosis at a younger age, may have other telomeropathy features, and may have different responses to certain treatments.

TGF-beta (transforming growth factor beta)

A signaling protein that plays a central role in stimulating scar-forming cells (fibroblasts) to produce collagen and other matrix proteins in the lung. TGF-beta is one of the master regulators of the fibrotic process. Several drugs in the IPF pipeline target TGF-beta or its downstream signaling pathways. Pirfenidone partially inhibits TGF-beta signaling as part of its mechanism of action.

TLC (total lung capacity)

The total amount of air the lungs can hold when fully inflated. TLC is reduced in pulmonary fibrosis (restrictive pattern) because stiff, fibrotic lungs cannot expand to their normal volume. TLC reduction confirms the restrictive pattern seen in fibrotic lung diseases, distinguishing them from obstructive diseases like COPD where TLC is normal or increased.

Traction bronchiectasis

Abnormal widening and distortion of the airways (bronchi) caused by surrounding scar tissue pulling them open and stretching them. Traction bronchiectasis is a key radiological feature of pulmonary fibrosis on HRCT and indicates significant fibrosis in the surrounding lung tissue. It is one of the findings that, together with honeycombing, defines the UIP pattern. Unlike the bronchiectasis caused by repeated infections, traction bronchiectasis is driven by the mechanical forces of scar tissue.

UIP (usual interstitial pneumonia)

The specific pattern of lung scarring that is the hallmark of IPF, seen on HRCT and/or lung biopsy. UIP is characterized by honeycombing, traction bronchiectasis, and reticulation predominantly in the lower lungs and near the outer edges (basal, subpleural distribution). A definite UIP pattern on HRCT in the right clinical context (appropriate age and history, known causes of ILD excluded) is sufficient to diagnose IPF without a lung biopsy. UIP indicates the most severe and most progressive form of lung scarring.

VEGFR (vascular endothelial growth factor receptor)

One of three types of growth factor receptors blocked by nintedanib. VEGF signaling promotes new blood vessel formation and, in the lung, also contributes to fibroblast activation. Blocking VEGFR is part of nintedanib’s antifibrotic mechanism. It is also responsible for the bleeding risk associated with nintedanib, because VEGF signaling is important for vascular integrity.

• University of Utah — Interstitial Lung Disease Program: A comprehensive, multidisciplinary ILD program with pulmonologists specializing in fibrotic lung disease, dedicated chest radiologists, and pathologists participating in formal multidisciplinary discussions (MDD). Part of the PFF Care Center Network. Offers antifibrotic therapy management, clinical trial access, pulmonary rehabilitation coordination, and direct pathways to the University of Utah Lung Transplant Program. Location: Salt Lake City, UT. Phone: 801-581-2121.
• Intermountain Health — Pulmonary and Critical Care Services: Multiple locations across the Wasatch Front providing pulmonary function testing, pulmonary rehabilitation programs, and general pulmonology. Can initiate diagnostic workup and refer to the University of Utah ILD program for specialized management. Pulmonary rehab programs available at Murray, Salt Lake City, and surrounding communities. Phone: 801-442-2000.

• National Jewish Health — Denver, CO: One of the leading respiratory hospitals in the world, with a dedicated ILD program, extensive clinical trial portfolio, and deep expertise in complex ILD diagnosis (including cases referred for second opinions from across the country). Part of the PFF Care Center Network. Particularly strong in environmental and occupational lung disease evaluation.
• Mayo Clinic — Rochester, MN (also Scottsdale, AZ and Jacksonville, FL): A world-renowned multidisciplinary ILD program with integrated radiology, pathology, and pulmonology teams. Leading lung transplant program. Extensive research portfolio including genomic and biomarker studies in IPF. Part of the PFF Care Center Network at multiple sites.
• UCSF — Interstitial Lung Disease Program, San Francisco, CA: A major academic ILD center with deep expertise in connective tissue disease-related ILD, hypersensitivity pneumonitis, and IPF. Strong clinical trial program. Part of the PFF Care Center Network. Affiliated lung transplant program at UCSF Medical Center.

Many other academic medical centers across the US have excellent ILD programs. The PFF Care Center Network lists 85+ specialized programs nationwide — visit pulmonaryfibrosis.org to find one near you.

• George E. Wahlen VA Medical Center — Pulmonary Section: Provides pulmonary function testing, pulmonary rehabilitation, and general pulmonology services for eligible veterans. Veterans with suspected or confirmed ILD can be referred to the University of Utah ILD program through VA community care agreements. Veterans with occupational exposures (burn pits, asbestos, silica, Agent Orange) should ensure these are documented in their VA records, as they may qualify for service-connected disability benefits and may also be relevant to the ILD diagnosis. Phone: 801-582-1565.

If you are a veteran with pulmonary fibrosis, ask your VA pulmonologist about referral to a specialized ILD center and inquire about clinical trial eligibility through both VA and civilian programs.

• Canadian Pulmonary Fibrosis Foundation (CPFF): cpff.ca — The national patient advocacy organization for pulmonary fibrosis in Canada. Provides education, support group directories, research funding, and advocacy for improved access to antifibrotic therapies across Canadian provinces. Offers a patient registry and connects patients with specialized ILD centers across the country.
• St. Michael’s Hospital / Unity Health Toronto — ILD Program: A leading Canadian ILD referral center in Toronto with multidisciplinary ILD clinics, antifibrotic management, and clinical trial access.
• University Health Network (Toronto General Hospital) — Lung Transplant Program: One of the largest lung transplant programs in the world. Accepts referrals from across Canada for IPF patients requiring transplant evaluation.
• McGill University Health Centre (Montreal) — ILD Clinic: A major academic ILD program in Quebec with MDD capability and access to clinical trials.
• Vancouver General Hospital / UBC — ILD Program: The primary ILD referral center for British Columbia, with expertise in fibrotic lung diseases and coordination with the BC Transplant program.

Access to antifibrotic medications varies by province; CPFF can help navigate provincial formulary coverage.

• European IPF Patient Charter: A collaborative initiative between patient organizations, clinicians, and policymakers across Europe that advocates for timely diagnosis, equitable access to antifibrotic therapy, multidisciplinary care, and clinical trial participation for IPF patients in all European countries. The charter has been endorsed by the European Respiratory Society (ERS) and multiple national respiratory societies.
• Action for Pulmonary Fibrosis (APF) — United Kingdom: actionpf.org — The leading UK charity for pulmonary fibrosis. Provides patient and carer support, funds research, and campaigns for better care and faster diagnosis. Offers a support line, information resources, and connections to specialist ILD centers across England, Scotland, Wales, and Northern Ireland.
• Royal Brompton Hospital — London, UK: One of the world’s leading respiratory centers with a dedicated ILD service, multidisciplinary team, and extensive clinical trial portfolio. Part of Guy’s and St Thomas’ NHS Foundation Trust.
• Universitätsklinikum Essen — Ruhrlandklinik, Germany: A major European ILD and lung transplant center with expertise in IPF diagnosis, antifibrotic management, and clinical trial enrollment.
• Toranomon Hospital / Jichi Medical University — Japan: Leading Japanese ILD programs with extensive real-world antifibrotic experience (Japan has the longest pirfenidone experience globally, since 2008). Japan’s KL-6 biomarker-integrated approach is a model for precision monitoring.

Many countries have national PF or ILD patient organizations. The European Lung Foundation (europeanlung.org) maintains a directory of patient organizations across Europe. In Australia, Lung Foundation Australia provides similar support.

• Manufacturer patient assistance programs. Both Boehringer Ingelheim (maker of nintedanib/Ofev and nerandomilast/Jascayd) and Genentech/Roche (maker of pirfenidone/Esbriet) offer patient assistance programs that can significantly reduce or eliminate out-of-pocket medication costs for eligible patients. These programs exist for both insured and uninsured patients. Contact the manufacturer directly or ask your pulmonologist’s office to help you apply. For Boehringer Ingelheim: 1-844-276-8262. For Esbriet Access Solutions: through Genentech.
• Copay assistance cards. Manufacturer copay cards can reduce monthly out-of-pocket costs to as little as $0 for commercially insured patients. These apply to most private insurance plans but typically cannot be used with government insurance (Medicare, Medicaid). Ask your pharmacist or specialty pharmacy coordinator about current copay assistance offers.
• Independent foundations. The HealthWell Foundation, Patient Advocate Foundation, and Patient Access Network (PAN) Foundation provide financial assistance to patients with chronic illnesses including pulmonary fibrosis. Eligibility is based on income and insurance status. A social worker at your ILD center can help you identify and apply for these programs.
• Medicare Part D assistance. If you are on Medicare, the standard Part D plan may still leave significant copayment gaps for specialty drugs. Extra Help (Low Income Subsidy) is a federal program that reduces or eliminates Medicare drug costs for qualifying low-income beneficiaries. The Medicare State Pharmaceutical Assistance Programs (SPAPs) in some states provide additional drug cost help.
• State pharmaceutical assistance programs. Some states have programs specifically designed to help residents afford high-cost medications. These vary widely by state; your pharmacist, social worker, or state health department can provide information.

• Social Security Disability Insurance (SSDI). If pulmonary fibrosis has prevented you from working, you may qualify for Social Security disability benefits. IPF can qualify under Social Security’s Compassionate Allowances program for very severe cases, which expedites the application process. Apply as soon as you become unable to work — there is a 5-month waiting period before benefits begin, and the application process itself can take several months. A disability attorney can help navigate the process and often works on a contingency basis (no fee unless benefits are awarded).
• Short-term and long-term disability insurance. If your employer provides disability insurance or you purchased private disability insurance, review your policy to understand your eligibility. Some policies have exclusions for pre-existing conditions.
• COBRA and the Affordable Care Act. If you need to leave your job due to IPF, COBRA extends your employer-sponsored insurance coverage for up to 18 months, though it can be expensive (you pay the full premium). The ACA marketplace offers subsidized insurance plans for those who qualify based on income.
• Legal protections. The Americans with Disabilities Act (ADA) requires employers with 15 or more employees to provide reasonable accommodations for qualified employees with disabilities. Reduced hours, work-from-home arrangements, modified duties, or schedule flexibility may be available. Contact your HR department or the Equal Employment Opportunity Commission (EEOC) for guidance.
• Lung transplant financial planning. Lung transplants are extremely expensive (surgery, hospitalization, post-transplant medications, and follow-up care can total several hundred thousand dollars or more). Medicare covers lung transplants performed at Medicare-certified centers, and most private insurers cover them as well, but copayments and deductibles can still be substantial. Transplant centers typically have social workers and financial counselors who specialize in helping patients navigate coverage and assistance programs.

The approval of nerandomilast (Jascayd) as an add-on to existing antifibrotics has opened the door to combination therapy — using two antifibrotic drugs with different mechanisms simultaneously to achieve greater slowing of fibrosis than either drug alone. This is analogous to combination chemotherapy in oncology or combination antiretroviral therapy in HIV.

• Nerandomilast + nintedanib: The FIBRONEER trials included patients already on nintedanib, demonstrating that the combination is feasible. Diarrhea rates may be higher with the combination (up to 62% in some subgroups), but discontinuation rates remained manageable. This is currently the most accessible combination strategy.
• Nerandomilast + pirfenidone: Also studied in FIBRONEER. The nerandomilast prescribing information specifies that no dose adjustment is needed when combined with pirfenidone.
• Future combinations: As new agents are approved, triple or sequential combination regimens may become standard, similar to the evolution of treatment in other progressive diseases.

If your disease is progressing despite a single antifibrotic, discuss combination therapy with your pulmonologist. Adding nerandomilast to an existing regimen is now an evidence-based option.

Several promising molecular targets are being pursued in clinical trials:

• Autotaxin inhibitors: Autotaxin is an enzyme that produces lysophosphatidic acid (LPA), a lipid signaling molecule that drives fibroblast activation, collagen production, and fibrosis. Multiple autotaxin inhibitors are in clinical development for IPF and other fibrotic diseases, representing one of the most actively pursued new antifibrotic mechanisms.
• Galectin-3 inhibitors: Galectin-3 is a protein involved in fibroblast activation, macrophage polarization, and extracellular matrix remodeling — key processes in fibrosis progression. Inhibitors targeting galectin-3 are in early- to mid-stage clinical trials for IPF and other organ fibroses (liver, kidney). Preclinical data suggest this pathway is particularly relevant to the inflammatory-fibrotic interface.
• Integrin inhibitors: Integrins are cell-surface proteins that activate TGF-beta, one of the master regulators of fibrosis. Although bexotegrast (an integrin inhibitor) was discontinued in 2025 due to safety concerns, other integrin-targeting agents remain in development. The pathway remains a high-priority target.
• Pentraxin-2 and macrophage reprogramming: Approaches that aim to shift macrophages from a pro-fibrotic to an anti-fibrotic phenotype continue to be explored, despite the failure of zinpentraxin alfa in Phase 3.

Delivering antifibrotic drugs directly to the lungs via inhalation is an appealing strategy that could maximize drug concentration at the site of disease while minimizing systemic side effects (particularly the gastrointestinal problems that limit oral antifibrotics). Several inhaled approaches are in development:

• Inhaled pirfenidone: Aerosolized formulations of pirfenidone are being investigated, aiming to achieve high lung tissue concentrations without the nausea and photosensitivity caused by oral pirfenidone.
• Inhaled antifibrotic nanoparticles: Novel delivery systems using nanoparticle carriers to target antifibrotic agents specifically to fibrotic lung tissue are in preclinical and early clinical development.
• Inhaled anti-inflammatory agents: Various inhaled formulations targeting specific inflammatory pathways in the lung are under investigation.

Inhaled therapies are still in relatively early development for IPF, but they represent a promising direction that could eventually offer better-tolerated treatment options.

Finding relevant clinical trials is an important step for patients whose disease is progressing or who want to contribute to advancing treatment.

ClinicalTrials.gov search guidance:

• Visit ClinicalTrials.gov and use the search bar
• Search terms to try: idiopathic pulmonary fibrosis, progressive pulmonary fibrosis, IPF antifibrotic, pulmonary fibrosis inhaled therapy, IPF autotaxin, IPF galectin
• Filter by Status: Recruiting to see only trials currently accepting participants
• Filter by Location to find trials near you (try your state or city)
• Filter by Phase (Phase 2 and Phase 3 trials are most likely to lead to new treatments)
• Look for trials that allow continuation of background antifibrotic therapy — many do

Other trial-finding resources:

• Pulmonary Fibrosis Foundation Clinical Trial Finder: A patient-friendly search tool at pulmonaryfibrosis.org
• Your ILD specialist: Academic ILD centers are often trial sites — ask what is available at your center or nearby
• Boehringer Ingelheim trial registry: The maker of nintedanib and nerandomilast maintains a registry of their sponsored trials