Diffuse Parenchymal Lung Diseases With an Unknown Cause
Pulmonary and Critical Care Medicine · Diffuse Parenchymal Lung Disease · study mode — pick an answer, then reveal.
Question · easy
A 67-year-old man with a 40-pack-year smoking history reports 8 months of chronic dry cough and progressive exertional dyspnea. Examination shows bibasilar Velcro-like end-inspiratory crackles and digital clubbing. HRCT demonstrates bilateral subpleural, basal- and posterior-predominant reticular abnormalities with honeycombing and traction bronchiectasis; there is no extensive ground-glass opacification, micronodules, or upper-lobe predominance. Which is the most appropriate next step?
A classic UIP pattern on HRCT (subpleural, basal-predominant reticulation with honeycombing) in the right clinical setting (age >50, smoking history, Velcro crackles, clubbing) is diagnostic of IPF without biopsy, and antifibrotic therapy slows FVC decline by roughly half while early transplant referral is advised. Surgical biopsy is unnecessary when the HRCT pattern is classic and adds procedural risk. Prednisone plus azathioprine (with NAC) was stopped early in a landmark trial for increased deaths and hospitalizations in IPF, and antibiotics do not treat this chronic fibrotic process.
MKSAP 19 B.5 Ch.3; Harrison's 22e Ch.304
Question · medium
A previously well 42-year-old woman develops progressive dyspnea and fever over 10 days following a viral prodrome, culminating in acute hypoxemic respiratory failure requiring mechanical ventilation. HRCT shows diffuse bilateral alveolar opacities. Lung biopsy reveals diffuse alveolar damage. Cultures are negative, and there is no history of sepsis, aspiration, trauma, transfusion, or pancreatitis. What is the most likely diagnosis?
AIP is clinically, radiographically, and pathologically indistinguishable from ARDS — diffuse alveolar damage with acute respiratory failure and bilateral opacities — and is distinguished from ARDS solely by the absence of ARDS risk factors; mortality is approximately 50% and management is supportive critical care. COP presents subacutely with patchy, often migratory consolidation that responds briskly to glucocorticoids rather than fulminant DAD. An acute exacerbation of IPF requires pre-existing UIP-pattern fibrosis, and cellular NSIP is a subacute, steroid-responsive interstitial pneumonia, not diffuse alveolar damage.
MKSAP 19 B.5 Ch.3; Harrison's 22e Ch.304
Question · medium
A 58-year-old man has had cough, low-grade fever, and malaise for 2 months. He was treated twice for community-acquired pneumonia with antibiotics without improvement. HRCT shows patchy, partly migratory subpleural consolidation and ground-glass opacities, including a reversed halo (atoll) sign. Biopsy demonstrates organizing pneumonia, and no cause is identified. He is started on prednisone and improves dramatically within days. What is the best management plan?
COP responds briskly — often dramatically — to glucocorticoids, but relapse during tapering is common, so treatment is typically continued for at least 6 months, with steroid-sparing agents (mycophenolate, cyclophosphamide, rituximab) reserved for relapsing disease or steroid toxicity. A 2-week course would invite relapse. Antifibrotics have no role in COP, which is an inflammatory rather than a progressive fibrotic process, and glucocorticoids are the treatment of choice rather than harmful.
MKSAP 19 B.5 Ch.3
Question · easy
A 28-year-old Black woman presents with fever, painful erythematous shin nodules (erythema nodosum), and migratory ankle arthritis. Chest radiography shows bilateral hilar lymphadenopathy with normal lung parenchyma; she has no weight loss, night sweats, or respiratory symptoms. What is the most appropriate next step?
Löfgren syndrome — bilateral hilar lymphadenopathy with erythema nodosum, migratory polyarthralgia/arthritis, and fever — carries such a favorable, self-limited course that tissue confirmation is not required, and observation with follow-up is appropriate (as with asymptomatic bilateral hilar lymphadenopathy and Scadding stage I disease, where >90% resolve spontaneously). EBUS-guided biopsy is warranted in other presentations where noncaseating granulomas must be demonstrated and mimics excluded. Glucocorticoids are first-line only when therapy is indicated for symptoms or organ dysfunction, and methotrexate is a second-line steroid-sparing agent, not initial management.
MKSAP 19 B.5 Ch.3; Harrison's 22e Ch.304
Question · hard
A 61-year-old woman with biopsy-confirmed fibrotic NSIP has taken mycophenolate and low-dose prednisone for 18 months. Over the past year she reports worsening exertional dyspnea, HRCT shows increased reticulation with new traction bronchiectasis, and FVC has fallen by 9% of predicted. According to the 2022 ATS/ERS/JRS/ALAT guideline, which is the most appropriate recommendation?
The 2022 guideline defines progressive pulmonary fibrosis (PPF) as at least two of three criteria — worsening respiratory symptoms, radiologic progression, or physiologic decline (FVC or DLCO) — within 1 year in a patient with a non-IPF ILD; this patient meets all three despite immunosuppression, and nintedanib is conditionally recommended because it slows lung-function decline in PPF (the nerandomilast FIBRONEER-ILD trial later reinforced antifibrotic benefit in PPF). The same guideline conditionally recommends against antacid medication and antireflux surgery as treatment for fibrotic lung disease. Riociguat was stopped early for harm in group 3 pulmonary hypertension and is contraindicated in PH-ILD, and PPF by definition applies to non-IPF ILDs such as fibrotic NSIP, so withholding antifibrotic therapy is incorrect.
Raghu, Am J Respir Crit Care Med 2022; Richeldi, N Engl J Med 2025