CONTENTS

• Septal thickening
  • Nodular septal thickening
• Crazy paving
• Fibrosis (including honeycombing)
• Questions & discussion

abbreviations used in the pulmonary section

• AE-ILD: Acute exacerbation of ILD 📖
• AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
• ANA: Antinuclear antibody 📖
• ANCA: Antineutrophil cytoplasmic antibodies 📖
• ARDS: Acute respiratory distress syndrome 📖
• ASS: Antisynthetase Syndrome 📖
• BAL: Bronchoalveolar lavage 📖
• BiPAP: Bilevel positive airway pressure 📖
• COP: Cryptogenic organizing pneumonia 📖
• CPAP: Continuous positive airway pressure 📖
• CPFE: Combined pulmonary fibrosis and emphysema 📖
• CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
• CTEPH: Chronic thromboembolic pulmonary hypertension 📖
• DAD: Diffuse alveolar damage 📖
• DAH: Diffuse alveolar hemorrhage 📖
• DIP: Desquamative interstitial pneumonia 📖
• DLCO: Diffusing capacity for carbon monoxide 📖
• FEV1: Forced expiratory volume in 1 second 📖
• FVC: Forced vital capacity 📖
• GGO: Ground glass opacity 📖
• GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
• HFNC: High flow nasal cannula 📖
• HP: Hypersensitivity pneumonitis 📖
• IPAF: Interstitial pneumonia with autoimmune features 📖
• IPF: Idiopathic pulmonary fibrosis 📖
• IVIG: Intravenous immunoglobulin 📖
• LIP: Lymphocytic interstitial pneumonia 📖
• MCTD: Mixed connective tissue disease 📖
• NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
• NSIP: Nonspecific interstitial pneumonia 📖
• NTM: Non-tuberculous mycobacteria 📖
• OP: Organizing pneumonia 📖
• PAP: Pulmonary alveolar proteinosis 📖
• PE: Pulmonary embolism 📖
• PFT: Pulmonary function test 📖
• PPFE: Pleuroparenchymal fibroelastosis 📖
• PPF: Progressive pulmonary fibrosis 📖
• PVOD/PCH Pulmonary venoocclusive disease/pulmonary capillary hemangiomatosis 📖
• RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
• TNF: tumor necrosis factor
• UIP: Usual Interstitial Pneumonia 📖

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septal thickening

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interlobular septal thickening

• This generates well-defined polygonal thickening that outlines the secondary pulmonary lobules.
• Septal thickening is most easily identified in places where the septa are best developed: the apices, bases, subpleural space, and areas adjacent to fissures. (Shepard 2019)
• Coronal reformatted images may help confirm this finding.

causes of interlobular septal thickening

[#1/4] edematous thickening

• Vascular congestion:
  • Heart failure.
  • Pulmonary venous obstruction, for example:
    • Fibrosing mediastinitis.
    • Pulmonary veno-occlusive disease.
    • Pulmonary vein stenosis s/p AF ablation or surgery.
• DAD (diffuse alveolar damage).
• DAH (diffuse alveolar hemorrhage) 📖
  • Septal thickening develops over time.
  • This is almost invariably accompanied by ground-glass opacification (which may generate a crazy-paving pattern).(15459632)
• Infection, including:
  • Mycoplasma.
  • Viral pneumonia (e.g., hantavirus, CMV, influenza).
  • Pneumocystis.
• Eosinophilic pneumonia:
  • AEP (acute eosinophilic pneumonia).
  • EGPA (eosinophilic granulomatosis with polyangiitis).

[#2/4] malignant/infiltrative septal thickening

• *Lymphangitic spread of malignancy:
  • *Lymphangitic carcinomatosis. 📖
  • *Lymphangitic spread of lymphoma or leukemia may also occur.
• *Kaposi sarcoma.
• *Amyloidosis.
• PTLD (posttransplant lymphoproliferative disease). 📖

[#3/4] fibrotic septal thickening

• Causes:
  • IPF (idiopathic pulmonary fibrosis).
  • CT-ILD (connective tissue-related interstitial lung disease).
  • Chronic radiation-induced lung injury.
  • Asbestosis.
• This is usually associated with other radiologic features of fibrosis (discussed further below: 📖).

[#4/4] other causes (rare)

• *Sarcoidosis (including sarcoid-like reaction to malignancy). However, this usually isn't the predominant finding. (34872679, Walker 2019)
• Acute lung rejection.
• Pulmonary alveolar proteinosis (septal thickening usually seen in combination with ground glass opacification).
• Erdheim-Chester disease.
• Diffuse pulmonary lymphangiomatosis. 📖
• Niemann Pick disease (suggested by a combination of septal thickening, ground-glass opacities, and micronodules).(32505326)
• Localized septal thickening near pleural inflammation (especially empyema or status post pleurodesis).(Walker 2019)
• *Dendriform pulmonary ossification (usually due to chronic gastric acid aspiration).

*nodular septal thickening

• Items marked with a red star may cause nodular septal thickening.
• If septal thickening is unequivocally nodular, then the differential diagnosis should focus on these entities.
• However, the absence of nodularity doesn't exclude any of these disorders. Nodularity can often be a subtle finding which is difficult to unequivocally discern.

• Key:
  • *Indicates the primary considerations in acute illness.
  • ^Indicates the primary considerations in subacute illness.

• *Cardiogenic pulmonary edema.
• *DAD (diffuse alveolar damage), often in the subacute phase.
• *DAH (diffuse alveolar hemorrhage; resolution phase after 7-10 days).(31704148)
• *Infection:
  • *Pneumocystis.
  • *Bacterial pneumonia (especially mycoplasma).
  • *Viral pneumonia (including COVID-19, hantavirus).
• Eosinophilic lung diseases:
  • *AEP (acute eosinophilic pneumonia).
  • ^CEP (chronic eosinophilic pneumonia).
  • ^EGPA (eosinophilic granulomatosis with polyangiitis).
• *Exposure-related lung diseases
  • *Drug-induced pneumonitis (which may encompass NSIP or OP in many cases).
  • *EVALI.
  • ^Radiation-induced lung injury.
  • ^Lipoid pneumonia – suggested by basilar or posterior predominance (figures below).(Walker 2019)
• Interstitial lung diseases:
  • ^Subacute HP (hypersensitivity pneumonia).
  • ^Cellular NSIP (nonspecific interstitial pneumonia).
  • ^OP (organizing pneumonia).
  • ^Sarcoidosis.
• ^Malignancy:
  • ^Minimally invasive adenocarcinoma / lepidic invasive adenocarcinoma (formerly bronchioloalveolar carcinoma).
  • ^Lymphangitic carcinomatosis.
• ^PAP (pulmonary alveolar proteinosis) – suggested by chronicity and diffuse location.
• Rare:
  • ^Diffuse pulmonary lymphangiomatosis.
  • ^Lipid storage disorders (e.g., Niemann-Pick disease).(35809945)

approach to an acutely ill patient with crazy-paving: cognitive forcing strategy

• Numerous diseases are possible (as listed above) – but the following possibilities should always be considered.
• [#1/7] Cardiogenic edema:
  • Suggested by:
    • Left atrial area >25-30 cm² 📖.
    • Pleural effusion(s).
    • Symmetric pulmonary infiltrates.
  • Tests to consider:
    • Echocardiogram.
    • BNP level.
• [#2/7] Drug/inhalational/radiation exposure:
  • History is essential (including vaping).
• [#3/7] Acute eosinophilic pneumonia:
  • Suggested by:
    • Absolute eosinophil level >~300 (but eosinophilia may be absent).
    • Pleural effusion(s).
    • Recent exposure to medication associated with eosinophilic pneumonia. 📖
  • Tests to consider:
    • Bronchoscopy with BAL (bronchoalveolar lavage).
• [#4/7] Pneumocystis:
  • Suggested by:
    • Known HIV.
    • Immunosuppression (e.g., chronic steroid).
  • Tests to consider:
    • HIV serology.
    • Beta-d-glucan level.
    • Induced sputum or BAL for pneumocystis PCR.
• [#5/7] Pneumonia due to viral or atypical bacteria (e.g., mycoplasma, COVID, hantavirus):
  • Suggested by:
    • Infectious prodrome, symptoms.
  • Tests to consider:
    • Nasopharyngeal PCR for viruses.
• [#6/7] DAH (diffuse alveolar hemorrhage):
  • Suggested by:
    • Subacute or acute-on-chronic presentation (crazy-paving develops gradually in DAH).
    • Renal involvement (pulmonary-renal syndrome).
    • Hemoptysis.
    • Fall in hemoglobin concentration.
  • Tests to consider:
    • Urinalysis.
    • Inflammatory markers (CRP, ESR).
    • Serologies for DAH (diffuse alveolar hemorrhage). 📖
    • Bronchoscopy for serial lavage & hemosiderin-laden macrophages.
• [#7/7] DAD (diffuse alveolar damage):
  • Suggested by known triggers of DAD.
  • Suggested by rapid clinical deterioration.
  • Suggested by lack of an alternative etiology (diagnosis of exclusion).
• Therapeutic interventions to consider:
  • Diuresis.
  • Steroid.
  • Antimicrobial coverage of pneumocystis (e.g., trimethoprim-sulfamethoxazole).
  • Antimicrobial coverage of atypical pathogens (e.g., azithromycin or doxycycline).

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fibrosis

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radiological signs that suggest fibrosis

honeycombing:

• This is defined as clustered cystic air spaces with well-defined 1-3 mm walls, typically 3-10 mm large (but up to 25 mm). Adjacent cysts usually share walls. The distribution is generally subpleural, often in stacked rows.
• There is substantial inter-observer variation in reaching this diagnosis.(Murray 2022) If in doubt, the presence of other features of fibrosis supports a diagnosis of honeycombing (e.g., traction bronchiectasis).
• Honeycombing is highly specific for fibrosis. As such, it's a poor prognostic sign (across a variety of interstitial lung diseases).(Murray 2022)
• Exuberant honeycombing:
  • This refers to fibrosis wherein honeycombing constitutes >70% of the fibrotic portions of the lung. In essence, there is a disproportionate amount of honeycombing, as compared to other manifestations of fibrosis (e.g., traction bronchiectasis).
  • Exuberant honeycombing is suggestive of RA-ILD 📖 (rheumatoid arthritis-related interstitial lung disease). It may also be seen as a component of IPAF 📖 (interstitial pneumonia with autoimmune features).
• Anterior upper lobe sign:
  • This refers to anterior upper lobe-predominant fibrosis, with relative sparing of the remaining upper lobes and fibrosis of the lower lobes.
  • This suggests connective tissue-related interstitial lung disease (e.g., interstitial pneumonia with autoimmune features 📖).

intralobular lines seen on CT scan 

• Lung injury may lead to a tiny meshwork of intralobular lines that are seen within the pulmonary lobule.
  • ⚠️ There is no such thing as intralobular septae. Therefore the term “intralobular septal thickening” is erroneous. (Rosado-De-Christenson 2022) 
• Intralobular lines are often best seen along fissures, in the subpleural space, and surrounding bronchovascular bundles. (Shepard 2019) Lines are closer together than interlobular septae would be (e.g., a few mm from each other).
• Intralobular lines are usually due to fibrosis (especially if accompanied by other features of fibrosis, such as traction bronchiectasis, traction bronchiolectasis, and honeycombing).(Walker 2019) 

interlobular septal thickening

• These may be seen in fibrosis, often with an irregular configuration.
• However, interlobular septal thickening usually isn't a prominent feature of fibrosis on CT scan.

volume loss causing architectural distortion

• Traction bronchiectasis:
  • Bronchial dilation is generally irregular.
  • Traction bronchiectasis is associated with parenchymal abnormality and other features of fibrosis.
  • Traction bronchiectasis generally indicates the presence of irreversible fibrosis when it occurs within the context of chronic interstitial lung disease. However, traction bronchiectasis in more acute contexts may be reversible (e.g., organizing pneumonia, diffuse alveolar damage).
  • The differential diagnosis includes other types of (non-traction) bronchiectasis combined with a surrounding opacity.
• Traction bronchiolectasis: Dilated airways within 1-2 cm of the pleura.
• Cicatricial atelectasis: Pulmonary fibrosis causes contraction of an area of lung tissue. This causes distortion of surrounding vasculature, bronchi, hila, and/or diaphragm.

causes of fibrosis

all causes of fibrosis

• Key:
  • 🐝 indicates diseases that can cause honeycombing. 
  • = indicates diseases that may cause intralobular lines. 

• Interstitial lung disease:
  • 🐝 = IPF (idiopathic pulmonary fibrosis). 📖
  • 🐝 = Fibrotic NSIP (nonspecific interstitial pneumonia). 📖
  • 🐝 = CTD-ILD (connective tissue disease related ILD). 📖
  • 🐝 = Drug-related fibrosis.
  • 🐝 = Asbestosis. 📖
  • 🐝 = HP (hypersensitivity pneumonitis). 📖
  • 🐝 = Sarcoidosis, berylliosis. 📖
  • 🐝 PLCH (pulmonary Langerhans cell histiocytosis).
• Pneumoconiosis with progressive massive fibrosis:
  • Silicosis.
  • Coal workers pneumoconiosis.
• Infection:
  • Chronic infections such as:
    • Tuberculosis.
    • Nontuberculous mycobacteria.
    • Chronic fungal pneumonia.
  • Necrotizing pneumonia.
• = DAD (diffuse alveolar damage): Fibrosis may tend to develop in anterior, subpleural “baby” lung (due to ventilator-induced lung injury).
• Radiation-induced lung injury.

causes of fibrosis, based on distribution:

• Upper-lobe predominant:
  • Chronic HP (hypersensitivity pneumonitis).
  • Sarcoidosis, berylliosis.
  • PLCH (pulmonary Langerhans cell histiocytosis).
  • Mycobacterial infection (especially tuberculosis).
  • Pneumoconiosis (silicosis, coal workers pneumoconiosis).
• Lower-lobe predominant honeycombing generally reflects a pattern of UIP (usual interstitial pneumonia). This may be clinically associated with:
  • IPF (idiopathic pulmonary fibrosis).
  • CT-ILD (connective tissue-associated interstitial lung disease).
  • Asbestosis.
  • Drug-related fibrosis.
  • Fibrotic NSIP (nonspecific interstitial pneumonia).
• Fibrosis that may spare the periphery:
  • Peribronchovascular honeycombing: Chronic HP (hypersensitivity pneumonitis), sarcoidosis.
  • NSIP (nonspecific interstitial pneumonia) may spare the periphery of the lung.

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questions & discussion

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