Interstitial Lung Disease — SAQ

Stem

A 68-year-old retired builder and lifelong smoker (40 pack-years) presents to the respiratory clinic with eight months of progressive exertional dyspnoea (now breathless after climbing one flight of stairs) and a persistent dry cough that disturbs his sleep. He has lost 6 kg. Examination reveals fine late-inspiratory crackles at both lung bases that do not clear with coughing (Velcro crackles), finger clubbing, SpO₂ 92% at rest dropping to 84% after a six-minute walk test, and a loud pulmonary component of S2.^[10]

Spirometry and lung volumes — FEV1 1.6 L (62% predicted), FVC 2.0 L (58% predicted), FEV1/FVC 0.80, TLC 65% predicted, DLCO 42% predicted.^[6]

HRCT thorax (thin-section, prone) — bilateral, basal and subpleural reticulation, honeycombing (clusters of subpleural cystic airspaces) and traction bronchiectasis, with no significant ground-glass change, no pleural plaques, no nodules.^[6]

ANA, ANCA, anti-Scl-70, anti-centromere, anti-Jo-1, anti-CCP and avian precipitins are negative. He has never received amiodarone, bleomycin, methotrexate, or nitrofurantoin.^[6]

Questions

a) What is the most likely diagnosis, and on what basis? (2 marks)

Idiopathic pulmonary fibrosis (IPF). Reasons: (i) elderly man who smokes with progressive exertional dyspnoea and dry cough (Kishaba); (ii) basal Velcro crackles and clubbing; (iii) restrictive defect (low TLC, low FVC, disproportionately low DLCO, preserved FEV1/FVC); (iv) HRCT shows a UIP pattern — bilateral, peripheral, basal reticular changes with traction bronchiectasis and clusters of subpleural cystic airspaces (Martinez); (v) exclusion of other ILDs or overlapping conditions (CTD serology negative, no drug/occupational/hypersensitivity history). Identify UIP usually on HRCT; biopsy is reserved for selected patients.^[6][10]

b) Name four HRCT features that would push you away from UIP toward an alternative ILD. (2 marks)

1. Mid/upper-zone predominance with poorly defined nodules and patchy air trapping (hypersensitivity pneumonitis).
2. Patchy consolidation that does not respond to antibiotics (organising pneumonia / COP).
3. Known antigen exposure plus an assemblage of clinical–radiologic–laboratory findings pointing to HP, not idiopathic UIP.
4. A CTD, drug, or occupational cause — the first job is always to exclude other ILDs. (The older "inconsistent with UIP" 2018 checklist — 3–10 mm cyst size, extensive GGO exceeding reticulation — is exam convention, not a list in the cited 2022 abstract.)^[6][9][11]

c) Outline the stepwise definitive management of this patient, naming drugs and sourced doses. (3 marks)

1. Multidisciplinary team (MDT) confirmation of IPF. Cryobiopsy is a conditional alternative to surgical lung biopsy in experienced centres (ATS 2022); this HRCT already shows UIP, so biopsy is not required.^[1][6]
2. Antifibrotic therapy — choose one of:
   • Pirfenidone 2403 mg per day (ASCEND, 52 weeks) — gastrointestinal and skin-related adverse events more common than placebo, rarely leading to discontinuation.^[3]
   • Nintedanib 150 mg twice daily (INPULSIS) — diarrhoea 61.5 / 63.2 percent versus about 18 percent placebo; discontinuation less than 5 percent. Do not escalate to 300 mg twice daily (that dose is not the INPULSIS/INBUILD/SENSCIS dose).^[2]
3. Supportive oxygen for hypoxaemia; pulmonary rehabilitation; vaccinations. Named PaO₂/SpO₂/15-hour LTOT thresholds are BTS/NICE service conventions, not trial end-points here.^[1]
4. Early lung-transplant referral — the only intervention that replaces the fibrotic lung.^[6]
5. DO NOT give azathioprine + prednisolone + NAC — PANTHER-IPF: 8 versus 1 deaths and 23 versus 7 hospitalisations; stopped at mean 32 weeks.^[7]
6. DO NOT treat IPF with antacids or antireflux surgery — ATS 2022 conditional recommendations against both.^[1]

d) The patient returns six months later with sudden worsening dyspnoea over five days, new bilateral ground-glass on HRCT, no evidence of infection or heart failure. What is this and how is it framed? (2 marks)

Acute exacerbation of IPF. The International Working Group (2016) divides AE-IPF into triggered and idiopathic. Heart failure and volume overload are the key differentials to exclude (Kishaba). Management is largely supportive, with attention to treatment and prevention of exacerbations. In-hospital 50 percent mortality, 3–4 month post-AE survival, and methylprednisolone 0.5–1 g for 3 days are not in the cited abstract and are not marked as sourced figures.^[10]

e) Name one non-pharmacological intervention that can replace the fibrotic lung in advanced IPF. (1 mark)

Lung transplantation — the only intervention that replaces the fibrotic lung in advanced IPF. Pirfenidone and nintedanib decrease physiological progression; they do not reverse fibrosis (Martinez).^[6]

References14ShowHide

1. [1]Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline Am J Respir Crit Care Med, 2022.PMID 35486072
2. [2]Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis N Engl J Med, 2014.PMID 24836310
3. [3]King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis N Engl J Med, 2014.PMID 24836312
4. [4]Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases N Engl J Med, 2019.PMID 31566307
5. [5]Distler O, Highland KB, Gahlemann M, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease N Engl J Med, 2019.PMID 31112379
6. [6]Martinez FJ, Collard HR, Pardo A, et al. Idiopathic pulmonary fibrosis Nat Rev Dis Primers, 2017.PMID 29052582
7. [7]Raghu G, Anstrom KJ, King TE Jr Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis N Engl J Med, 2012.PMID 22607134
8. [8]Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial Lancet Respir Med, 2016.PMID 27469583
9. [9]Selman M, Pardo A, King TE Jr Hypersensitivity pneumonitis: insights in diagnosis and pathobiology Am J Respir Crit Care Med, 2012.PMID 22679012
10. [10]Kishaba T Acute Exacerbation of Idiopathic Pulmonary Fibrosis Medicina (Kaunas), 2019.PMID 30884853
11. [11]Sakthivel MK, Hazelton TR, Askin FB, et al. Organizing Pneumonia Phenotype Semin Roentgenol, 2026.PMID 41513514
12. [12]Naraoka T, Sumi T Management of drug-induced interstitial lung disease in the era of evolving lung cancer therapies: A mini-review Respir Investig, 2026.PMID 42520532
13. [13]Hino T, Lee KS, Yoo H, et al. Interstitial lung abnormality (ILA) and nonspecific interstitial pneumonia (NSIP) Eur J Radiol Open, 2021.PMID 33796637
14. [14]Ley B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis Ann Intern Med, 2012.PMID 22586007