Interstitial Lung Disease
By the end of this post you will be able to:
- Recognize interstitial lung disease at the bedside, distinguish it from heart failure and COPD, and select the initial investigations.
- Assess a patient with known interstitial lung disease who deteriorates in hospital, and exclude the reversible causes before treating an acute exacerbation.
- Distinguish idiopathic pulmonary fibrosis from the treatable non-IPF interstitial lung diseases, and name what each implies for long-term management.
TL;DR
What you need to know before seeing your first patient on your IM rotation with this condition
Estimated read time: 3 minutes
- What it is: Disease of the lung interstitium, not the airways or pleura — a family of conditions, not one diagnosis. You meet it two ways: an acute exacerbation of known ILD, or a new diagnosis in unexplained breathlessness.
- How it presents: Progressive exertional dyspnea over months, a dry cough, and fine bibasilar crackles — Velcro-like, and they do not clear with diuresis. Look for clubbing and desaturation on walking, then outside the chest: skin, joints, Raynaud phenomenon, proximal weakness.
- Initial tests to order: The two situations differ. New diagnosis: HRCT without contrast, full PFTs with DLCO, ambulatory oximetry, autoimmune serology. Acute exacerbation: HRCT, plus what chases the three reversible causes — CT pulmonary angiogram, cultures, viral swab, BNP and echocardiogram.
- Acute exacerbation of ILD: Apply supplemental oxygen first. Then exclude the three reversible causes — pulmonary embolism, infection, decompensated heart failure — before accepting the label. In consultation with respirology, consider corticosteroids — the common regimen is methylprednisolone 500–1000 mg IV daily for three days, then prednisone 0.5–1 mg/kg PO with a taper, though no guideline gives a dose. Mortality is high — ask about escalation early.
- New diagnosis of ILD: Complete the workup, refer to ILD clinic, and do not start immunosuppression from the ward — the diagnosis is made at multidisciplinary discussion, and immunosuppression can cause harm in IPF. Nintedanib and pirfenidone are the typical treatments once IPF is confirmed.
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Read Around the Case
Based on the Canadian Thoracic Society position statement on the evaluation of fibrotic ILD (2017), the CTS position statement on comprehensive management of fibrotic ILD (2018), and the ATS/ERS/JRS/ALAT guideline on IPF and progressive pulmonary fibrosis (2022).
Estimated read time: 15 minutes
1. Recognizing ILD, and Confirming the Diagnosis
Estimated read time: 3 minutes
The ILD Sequence
Months of exertional dyspnea, dry cough and fine Velcro crackles
Chest radiograph first — but it is often normal early, so a clear film does not exclude ILD
HRCT chest, WITHOUT contrast
Reticulation · ground-glass · honeycombing · traction bronchiectasis — and where they sit
Full PFTs with DLCO · ambulatory oximetry
Expect restriction with a low DLCO
Autoimmune serology · exposure history · medication review
This is the step that decides everything below
Respirology + thoracic radiology + pathology together
The diagnostic standard — not any single test
The CTS evaluation statement frames the first task as separating four broad groups, because they are treated differently:
- Idiopathic — IPF and the other idiopathic interstitial pneumonias.
- Connective-tissue-disease-associated — rheumatoid arthritis, systemic sclerosis, myositis, Sjögren syndrome.
- Exposure-related — hypersensitivity pneumonitis and the pneumoconioses.
- Drug-induced, with sarcoidosis sitting alongside the four as a granulomatous disease.
What it gets mistaken for. Heart failure, pneumonia and ILD all produce bibasilar findings, and the label that arrives with the patient tends to stay. Two findings separate them:
- The pulmonary function report. Restriction with a reduced DLCO, where obstruction or volume overload was assumed. A patient labelled COPD who is restrictive on formal testing has been mislabelled.
- The time course. Pneumonia declares itself over days; ILD has usually been progressing for months before anyone measures it.
Why the CT must be without contrast. HRCT is a distinct protocol rather than a routine chest CT — thin sections, high-resolution reconstruction, and expiratory and prone sequences. Those sequences are what show air-trapping and what separates dependent atelectasis from early basal fibrosis. Contrast adds nothing to the interstitium and can obscure subtle ground-glass — it belongs here only when the question is vascular.
The history is deliberately not on that table. It is not a test you order — it is one you take, and it is the only part of the workup that can find a cause you are able to remove. Work through the exposures listed in section 4, and read the medication list yourself rather than relying on what the patient recites.
2. Idiopathic Pulmonary Fibrosis, and Long-Term Antifibrotic Therapy
Estimated read time: 3 minutes
IPF is a diagnosis of exclusion — a UIP pattern on HRCT plus a search for a cause that has come back empty:
- No connective tissue disease on serology.
- No inhaled exposure, and no culprit drug.
- No sarcoidosis or other identified alternative.
The exclusion has to be done properly, because the label decides the drug. Two oral antifibrotics slow its progression. INPULSIS randomized 1,066 patients to nintedanib or placebo across two replicate 52-week trials, and annual FVC decline fell from −239.9 to −114.7 mL in the first trial and from −207.3 to −113.6 mL in the second. ASCEND showed the same direction of effect for pirfenidone.
What they do, and what they do not. Worth saying plainly to a patient who expects to feel better on starting them:
- They do not improve symptoms, and do not reverse established fibrosis.
- The reduction in acute exacerbations seen in one INPULSIS trial was not reproduced in its twin.
Steroids are the wrong reflex in IPF
PANTHER-IPF tested prednisone, azathioprine and N-acetylcysteine together against placebo in IPF. The combination arm was stopped early for increased death and hospitalization. Immunosuppression helps in several of the non-IPF interstitial lung diseases, which is exactly why it gets reached for here — but in IPF the fibrosis is not driven by inflammation, and treating it as though it were causes harm. Establish which ILD you are treating before prescribing.
Trial Files
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3. The Non-IPF ILDs, and What Changes Their Course
Estimated read time: 4 minutes
Hypersensitivity pneumonitis is an immune response to an inhaled antigen, and it is the ILD where the history does more than any test. The ATS/JRS/ALAT diagnostic guideline (2020) builds the diagnosis from exposure identification, HRCT pattern and bronchoalveolar lavage lymphocytosis; mosaic attenuation with air-trapping on expiratory images is the radiological clue. Removing the antigen is what changes the trajectory — section 4 lists what to ask about.
Connective-tissue-disease-associated ILD is where immunosuppression earns its place. In systemic sclerosis, Scleroderma Lung Study II found mycophenolate as effective as oral cyclophosphamide and better tolerated, and SENSCIS showed nintedanib also slows FVC decline in this group. For a resident on a medical ward the task is recognition and referral, not selecting the agent.
Drug-induced ILD is the one cause you can act on the same day, by stopping the drug. It is easy to miss because the presentation is indistinguishable from the others and the culprit is usually a medication the patient has tolerated for a long time.
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Progressive pulmonary fibrosis is not another diagnosis. It is a description of how a disease is behaving, and it cuts across all the ILDs in this section.
Most non-IPF ILDs have an identifiable driver, so treatment means removing or suppressing it: take the bird out of the house, stop the drug, treat the connective tissue disease. In many patients that works and the disease stabilizes. In others it does not — the fibrosis carries on regardless, as though it has become self-sustaining and no longer needs the original trigger. That is what the term names.
Why it matters: a disease behaving this way has stopped being an inflammatory problem and started resembling IPF, so it responds to an antifibrotic rather than to more immunosuppression. The ATS/ERS/JRS/ALAT guideline (2022) makes it a formal category so that decision can be made consistently, defining it as at least two of three criteria within the past year, with no alternative explanation:
- Worsening respiratory symptoms.
- Radiological progression on HRCT.
- Physiological progression — a falling FVC or DLCO.
INBUILD established this. It enrolled patients by behaviour rather than by diagnosis — a mixed group with rheumatoid ILD, hypersensitivity pneumonitis and others, all progressing — and randomized them to nintedanib or placebo. FVC declined more slowly on nintedanib, which is the basis for the guideline’s conditional recommendation in this group.
Sarcoidosis
A granulomatous disease that reaches the lung in most patients, classically with bilateral hilar lymphadenopathy and upper-zone predominant change — the reverse of the basal distribution of UIP. Many patients need no treatment at all, and the decision to treat rests on symptoms and organ involvement rather than on the radiograph.
Prednisone has been the conventional first-line drug. Although this can vary with local practice and physician comfort, it is worth noting that PREDMETH (NEJM 2025) randomized 138 treatment-naive patients with pulmonary sarcoidosis to prednisone 40 mg daily tapered to 10 mg daily or methotrexate 15 mg weekly increased to 25 mg weekly, each for 24 weeks.
Methotrexate was noninferior for change in percent-predicted FVC at 24 weeks, with an adjusted between-group difference of −1.17 percentage points (95% CI −4.27 to 1.93). Adverse events occurred at a similar rate but differed in kind: weight gain, insomnia and increased appetite with prednisone; nausea, fatigue and abnormal liver-function tests with methotrexate.
4. Living with ILD — the Non-Drug Management
Estimated read time: 3 minutes
Most of what changes a patient’s day-to-day life with interstitial lung disease is not a prescription. The CTS statement on comprehensive management is built around this, and it is the part of the topic most often left to the clinic letter.
5. Practical Considerations for an Outpatient
Estimated read time: 2 minutes
After a flare, arrange all of this before discharge:
- Repeat physiology, to re-baseline against the pre-admission numbers.
- An ILD clinic appointment.
- An oxygen reassessment, on exertion.
- Pulmonary rehabilitation, if function was lost during the admission.
Then the ongoing pattern. The CTS statement on long-term monitoring sets it, and the baseline you ordered on the ward is what it is measured against:
- Full PFTs with DLCO every three to six months in the first year, then at intervals guided by stability. Repeat imaging when the numbers or the symptoms change, not on a fixed schedule.
- A falling FVC or DLCO defines progression — and moves a non-IPF ILD into the progressive pulmonary fibrosis group.
- Lung transplant assessment is referred earlier than most people expect. In IPF the trajectory is unpredictable and waiting-list time is real, so a candidate goes around the time of diagnosis rather than when they deteriorate.
- Advance care planning belongs in the current admission, given a prognosis comparable to several common cancers. Palliative care alongside active treatment is appropriate, and is not a signal that treatment has stopped.
Related Podcasts
Two episodes that sit either side of this topic — the connective tissue disease behind a common CTD-ILD, and where patients with advanced disease are referred.
Test Yourself
Click on your answer to reveal the explanation.
A 71-year-old man with idiopathic pulmonary fibrosis diagnosed 18 months ago is admitted with four days of worsening breathlessness. His blood pressure is 126/74 mmHg and has been stable, heart rate 96, temperature 37.1°C. He now needs 5 L/min by nasal prongs to maintain a saturation of 91%, having been on no oxygen at home. There is no chest pain, no leg swelling and no purulent sputum. HRCT shows new bilateral ground-glass opacity superimposed on his known basal reticulation and honeycombing.
What is the most appropriate next step?
A 68-year-old woman is reviewed after a multidisciplinary discussion confirmed idiopathic pulmonary fibrosis. Her HRCT shows a definite UIP pattern, autoimmune serology including ANA, RF, anti-CCP, ENA and a myositis panel is negative, and there is no occupational, environmental or drug exposure. She is clinically stable, her blood pressure is 132/78 mmHg, and her FVC is 74% predicted with a DLCO of 52% predicted.
What is the most appropriate long-term treatment to arrange?
Reflect
A 72-year-old man has carried a diagnosis of COPD for four years. He has a 30 pack-year history, is on triple inhaled therapy, and has become steadily more breathless over the past two years despite good adherence. Reviewing his chart you find pulmonary function tests from eight months ago showing an FVC of 68% predicted, a TLC of 71% predicted, an FEV1/FVC ratio of 0.82 and a DLCO of 45% predicted. At what point should the existing label be questioned, and what would you do next?
Please do not include patient identifying details — no names, initials, dates, medical record numbers, or any detail that could identify a specific patient or encounter. Write about your reasoning, not about a real person.
Further Reading
- GuidelineEvaluation of Patients with Fibrotic Interstitial Lung Disease — CTS Position Statement (2017)
- GuidelineComprehensive Management of Fibrotic Interstitial Lung Disease — CTS Position Statement (2018)
- GuidelineLong-Term Monitoring of Patients with Fibrotic Interstitial Lung Disease — CTS Position Statement (2020)
- GuidelineIdiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in Adults — ATS/ERS/JRS/ALAT (2022)
- GuidelineDiagnosis of Hypersensitivity Pneumonitis in Adults — ATS/JRS/ALAT (2020)
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