4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema
Key Takeaways
Diffuse alveolar hemorrhage is confirmed when sequential bronchoalveolar lavage aliquots become progressively bloodier; hemoptysis is absent in up to a third of patients.
Anti-GBM disease with alveolar hemorrhage is treated with plasma exchange plus pulse corticosteroids and cyclophosphamide.
In ANCA vasculitis, the PEXIVAS trial (2020) found that plasma exchange did not reduce death or end-stage kidney disease.
In the EXAFIP trial (2020), adding intravenous cyclophosphamide to steroids increased 3-month mortality in acute exacerbation of idiopathic pulmonary fibrosis.
Negative-pressure pulmonary edema follows forceful inspiration against an obstructed upper airway and usually resolves within 24 to 48 hours with supportive care.
Diffuse Alveolar Hemorrhage (DAH)
DAH is bleeding into the alveolar spaces from injury to the alveolar-capillary membrane. The classic triad is hemoptysis, a falling hemoglobin, and diffuse bilateral infiltrates. Hemoptysis is absent in up to a third of patients, so DAH must be considered in any unexplained diffuse infiltrate with anemia.
- Diagnosis: bronchoalveolar lavage (BAL) in one subsegment returns progressively bloodier aliquots. Hemosiderin-laden macrophages appear after about 48 to 72 hours, with more than 20% supporting the diagnosis.
- Three histologic patterns:
- Pulmonary capillaritis: neutrophilic destruction of the capillaries. Causes include ANCA-associated vasculitis, anti-GBM disease, lupus, antiphospholipid syndrome, and drugs such as propylthiouracil and levamisole-contaminated cocaine.
- Bland hemorrhage: anticoagulants or thrombolytics, severe thrombocytopenia, mitral stenosis, and high left atrial pressure.
- Diffuse alveolar damage with hemorrhage: hematopoietic cell transplantation, infection, and toxic inhalation.
- Workup:
- Serology: ANCA (PR3 and MPO), anti-GBM antibody, ANA and anti-dsDNA, complements, and antiphospholipid antibodies.
- Kidney screen: creatinine and urinalysis for red cell casts. A pulmonary-renal syndrome strongly suggests vasculitis or anti-GBM disease.
- Coagulation studies and a platelet count.
- Tissue confirmation from kidney or skin biopsy when it can be obtained.
Treatment
- Supportive: lung-protective ventilation with adequate PEEP (which also tamponades bleeding), and correction of coagulopathy and thrombocytopenia. VV-ECMO can be used, with minimal anticoagulation.
- Immune capillaritis: pulse methylprednisolone (500 to 1,000 mg IV daily for 3 days), then induction with rituximab or cyclophosphamide for ANCA vasculitis (rituximab was noninferior in RAVE).
- Plasma exchange:
- Anti-GBM disease: plasma exchange is standard, combined with steroids and cyclophosphamide.
- ANCA vasculitis: the PEXIVAS trial (2020) found no reduction in death or end-stage kidney disease with plasma exchange, so its use in alveolar hemorrhage is individualized for the most severe cases.
Pulmonary Vasculitis and Pulmonary-Renal Syndromes
| Disease | Serology | Distinguishing features |
|---|---|---|
| Granulomatosis with polyangiitis | PR3-ANCA (c-ANCA) | Sinusitis, saddle-nose deformity, cavitating nodules, subglottic stenosis, glomerulonephritis |
| Microscopic polyangiitis | MPO-ANCA (p-ANCA) | Glomerulonephritis and DAH without granulomas |
| Eosinophilic granulomatosis with polyangiitis | MPO-ANCA in a minority | Late-onset asthma, eosinophilia, neuropathy, cardiomyopathy |
| Anti-GBM disease | Anti-GBM IgG (linear deposition on biopsy) | Smokers or inhalant exposure; rapid glomerulonephritis |
| Systemic lupus erythematosus | ANA, anti-dsDNA, low complement | DAH carries high mortality; also lupus pneumonitis and shrinking lung |
Interstitial Lung Disease in the ICU
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute worsening within about 1 month, with new bilateral ground-glass opacity or consolidation on a background of usual interstitial pneumonia, not fully explained by heart failure or fluid overload. In-hospital mortality is about 50%, and much higher with mechanical ventilation.
- Search for triggers: infection, aspiration, pulmonary embolism, pneumothorax, and drug toxicity.
- High-dose corticosteroids are commonly given, although the evidence is weak.
- In EXAFIP (2020), adding intravenous cyclophosphamide to steroids increased 3-month mortality.
- Intubation rarely leads to recovery unless lung transplantation is an option. Have early goals-of-care conversations, and reserve ECMO as a bridge to transplant in listed candidates.
Other ICU-relevant interstitial processes:
- Drug-induced pneumonitis:
- Amiodarone (with high lung attenuation on CT).
- Nitrofurantoin.
- Methotrexate.
- Bleomycin (worsened by high FiO2).
- Immune checkpoint inhibitors. Grade 3 or 4 pneumonitis requires stopping the drug and giving methylprednisolone 1 to 2 mg/kg; infliximab, mycophenolate, or IVIG are options if there is no response in about 48 hours.
- Acute interstitial pneumonia: idiopathic diffuse alveolar damage.
- Cryptogenic organizing pneumonia: steroid-responsive migratory consolidation.
- Hypersensitivity pneumonitis.
- Rapidly progressive ILD: for example, anti-MDA5 dermatomyositis.
Noncardiogenic Pulmonary Edema Other Than ARDS
| Type | Setting and mechanism | Course and management |
|---|---|---|
| Neurogenic | Subarachnoid hemorrhage, traumatic brain injury, seizures; catecholamine surge raises pulmonary capillary pressure and permeability | Onset within minutes to hours; usually resolves in 48 to 72 hours; supportive care and treatment of the brain injury |
| Negative-pressure (post-obstructive) | Forceful inspiration against a closed glottis: laryngospasm at extubation, choking, strangulation; young muscular patients | Resolves in 24 to 48 hours with oxygen, PEEP or CPAP, and supportive care |
| Tocolytic-associated | Beta-agonists (terbutaline) or magnesium in pregnancy, often with corticosteroids and generous fluids | Stop the tocolytic; diuresis and oxygen |
| High-altitude (HAPE) | Exaggerated, uneven hypoxic pulmonary vasoconstriction causes capillary stress failure, usually 2 to 4 days after rapid ascent | Descent and oxygen first; nifedipine as adjunct or prophylaxis |
| Re-expansion | Rapid re-expansion of a lung after drainage of a large effusion or pneumothorax | Limit drainage volume, stop if chest discomfort or cough develops; supportive |
| Other | Opioid overdose and naloxone reversal, salicylate toxicity, immersion, transfusion-related acute lung injury | Treat the cause; supportive ventilation |
Atelectasis
Atelectasis has four mechanisms:
- Obstructive: mucus plugging or a tumor, causing collapse with volume loss and an ipsilateral shift.
- Compressive: effusion, abdominal distension, or obesity.
- Adhesive: surfactant loss.
- Absorptive: high FiO2 washes out nitrogen.
Prevention and treatment combine mobilization, upright positioning, incentive spirometry, secretion clearance, adequate PEEP, and the lowest FiO2 that meets the oxygen target. Bronchoscopy is reserved for lobar collapse that does not respond to chest physiotherapy, or for a suspected central obstruction.
A 28-year-old man presents with hemoptysis, a hemoglobin of 7.9 g/dL (11 g/dL two days ago), bilateral alveolar infiltrates, and a creatinine of 4.6 mg/dL with red cell casts. He requires intubation. Sequential lavage aliquots become progressively bloodier, and anti-glomerular basement membrane antibody returns strongly positive with negative ANCA. In addition to pulse methylprednisolone, which therapy is most appropriate?
Plasma exchange together with cyclophosphamide
Rituximab alone without plasma exchange
Recombinant activated factor VII infusion
Inhaled tranexamic acid with ceftriaxone
A 24-year-old rugby player is extubated after knee surgery and develops laryngospasm that resolves after 90 seconds of jaw thrust and positive pressure. Thirty minutes later he has pink frothy sputum, bilateral infiltrates, and an oxygen saturation of 86% on room air. Echocardiography shows normal biventricular function. What is the most likely diagnosis and expected course?
Aspiration pneumonitis that will require broad-spectrum antibiotics for 7 days
Transfusion-related acute lung injury that will progress to severe ARDS
Negative-pressure pulmonary edema that usually resolves within 24 to 48 hours with supportive care
Takotsubo cardiomyopathy causing cardiogenic pulmonary edema that needs inotropes
A 74-year-old man with idiopathic pulmonary fibrosis has 10 days of worsening dyspnea. CT shows new bilateral ground-glass opacity superimposed on honeycombing; echocardiography and BNP do not suggest heart failure, and infectious studies are negative. He is not a lung transplant candidate. Which statement best guides management?
Adding intravenous cyclophosphamide to corticosteroids increases 3-month survival and should be started promptly
Mechanical ventilation in this setting usually leads to recovery, so early intubation is preferred over palliative discussions
Venovenous ECMO is indicated as destination therapy because the exacerbation is likely to reverse within weeks
Corticosteroids are commonly used despite weak evidence, and early goals-of-care discussion is essential because mortality is very high
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