Overview
Definition
- Interstitial lung disease (ILD) comprises a heterogeneous group of disorders that cause varying degrees of inflammation and fibrosis of the lung interstitium, the space between the capillary endothelium and the alveolar epithelium.
- Clinically, affected patients will show restrictive lung disease by pulmonary function studies.
Epidemiology
Idiopathic pulmonary fibrosis, sarcoidosis, and ILD associated with connective tissue diseases are the most common types of ILD.
Classification
It is useful to categorize ILDs into those with and without a known cause.
| Cause unknown | Cause known |
|---|---|
Idiopathic interstitial pneumonias (IIP):
| Systemic diseases
|
Diagnosis
History
| Age |
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|---|---|
| Sex |
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| Clinical presentation |
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| Symptoms |
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| Past medical history |
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| Drug history | Methotrexate, azathioprine, rituximab, tumor-necrosis factor blockers, amiodarone, nitrofurantoin, chemotherapeutics |
| Family history | Having a close relative with IIP is a strong risk factor for ILD, especially IPF. |
| Social history |
|
Physical examination
- End-inspiratory fine crackles in lung bases (common finding, especially in IPF)
- Wheezing is uncommon (may be found in HP, Churg-Strauss disease, sarcoidosis)
- Severe disease findings: cyanosis, digital clubbing, cor pulmonale
Laboratory studies
Autoantibody detection may help with the diagnosis of some CTDs.
Pulmonary function testing
- The diffusing capacity for carbon monoxide (DLCO) shows reduction.
- Most show a restrictive pattern.
Imaging
- Chest X-ray may be suggestive of a type of ILD:
- Peripheral reticular pattern in lower lung zones and small cystic spaces suggests IPF.
- Central nodular pattern in mid-to-upper lung zones and hilar lymph node enlargement suggests sarcoidosis.
- Chest computed tomography (CT):
- Standard initial test
- May confirm the diagnosis of IPF in the right setting and obviate the need for lung biopsy
- Better defines disease extent and features (e.g., honeycombing)
- Helps exclude comorbidities (e.g., pneumothorax) or differential diagnosis (e.g., malignancy)
- Helps determine the best location for biopsy
Lung biopsy
- Establishes the diagnosis
- Performed via fiberoptic bronchoscopy or surgery
- Biopsy is not needed if:
- High-resolution CT (HRCT) shows classic usual interstitial pneumonia and the patient has no systemic diseases suggestive of an another disorder.
- Patient has minimal signs or symptoms and a stable/nonprogressive disease.
- Indicated in cases of comorbidities or rapidly progressive symptoms
Individual Forms
Idiopathic pulmonary fibrosis
- Most common ILD of unknown cause
- Commonly diagnosed in 5th or 6th decade
- Affects men more than women
- Frequently associated with smoking
- 3–5-year survival rate is 50%.
- May be associated with acute exacerbations
- Lung HRCT shows a pattern of UIP: subpleural reticular pattern with posterior-basal predominance with more advanced fibrotic features such as honeycombing and traction bronchiectasis.
- Histopathology shows a pattern of UIP: subpleural reticulation, honeycombing, fibroblasts, skipped lesions with preserved architecture (temporal and spatial heterogeneity).
- Treatment: physical therapy and supplemental oxygen, antifibrotic therapy (pirfenidone), and lung transplantation if patient meets criteria
Typical HRCT pattern of UIP. The image shows subpleural and basal predominance of reticular opacities associated with traction bronchiectasis and honeycomb change (clustered cystic airspaces with well-defined thick walls and diameter of 0.3–1.0 cm)
. Image: “(HRCT) pattern” by Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK. License: CC BY 4.0
Posterior-anterior chest radiograph of a 67-year-old man with progressive dyspnea revealing bilateral reticular infiltrates with lower lobe predominance
Image: “PA chest radiograph of a 67-year old man” by Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Duke University Medical Center, Durham, North Carolina 27710, USA. License: CC BY 2.0
Photomicrograph of biopsy from a 63-year-old man with a multi-disciplinary diagnosis of IPF. The patient shows the typical histopathological features of usual interstitial pneumonia characterized by spatial heterogeneity with areas of subpleural and paraseptal fibrosis and honeycombing changes (cystic airspaces lined by bronchiolar epithelium) alternating with areas of relatively spared lung parenchyma, temporal heterogeneity with admixed areas of active fibrosis with fibroblast foci, extracellular matrix deposition (mainly collagen), and relatively mild or absence of inflammatory cell infiltrate together with regions of histologically normal lung tissue.
Image: “Photomicrograph of biopsy from a 63-year-old man with a multi-disciplinary diagnosis of idiopathic pulmonary fibrosis” by Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK. License: CC BY 4.0
Non-specific interstitial pneumonia
- May be idiopathic or commonly associated with CTDs
- Commonly diagnosed in non-smoking women in their 5th decade
- 5-year survival rate is 80%.
- Lung HRCT shows diffuse and symmetric subpleural ground-glass and reticular opacities; traction bronchiectasis may be seen; honeycombing and peribronchial thickening is uncommon.
- Histopathology shows uniform interstitial inflammation and fibrosis without honeycombing.
- Treatment: physical therapy, supplemental oxygen, steroids, immunosuppressive therapy, and lung transplantation if patient meets criteria
Drug-induced lung disease with am NSIP pattern. The patient has undergone chemotherapy for bladder cancer. Chest CT at the level of the right pulmonary artery at lung window. Diffuse bilateral peripheral reticular pattern, ground glass, and some consolidation.
Image: “Drug-induced lung disease” by Department of Diagnostic and Interventional Radiology, Marien Hospital, Academic Teaching Hospital, Rochusstr. 2, D- 40479, Düsseldorf, Germany. License: CC BY 4.0
Non-specific interstitial pneumonia. A mesh-like fibrosis of the alveolar septa is seen. Fibroblastic foci are not found. Aggregates of lymphocytes are sometimes found (HE, original magnification 40x).
Image: “Non specific interstitial pneumonia” by Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany. License: CC BY 2.0
Cryptogenic organizing pneumonia
- May be idiopathic or secondary to polymyositis, medications, or malignancy
- Commonly diagnosed in 6th or 7th decade
- Lung HRCT shows migratory, patchy, subpleural consolidations and ground-glass opacities with or without a rim of subpleural sparing known as the halo sign (characteristic).
- Treatment: steroids and immunosuppressives
A 59-year-old woman with a history of left breast cancer and radical mastectomy. The patient was diagnosed with radiotherapy- induced cryptogenic organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia). Computed tomography shows patchy areas in the left lung and in the middle lobe of the right lung.
Image: “Bronchiolitis obliterans organizing pneumonia” by Dept of Pulmonary Diseases, Sint Franciscus Gasthuis, Rotterdam, The Netherlands. License: CC BY 2.0Cryptogenic organizing pneumonia: In alveolar ducts and bronchioles, buds of granulation tissue are detected (HE, original magnification 100x).
Image: “Cryptogenic organizing pneumonia” by Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany. License: CC BY 2.0
Smoking-related ILD
- Occurs in heavy smokers in the 5th or 6th decade
- Honeycombing is typically absent
- Biopsy confirms diagnosis
- Treatment includes smoking cessation and immunosuppressive therapy
Connective tissue disease–associated ILD and granulomatous ILD
| IPF | Systemic sclerosis–associated ILD | Sarcoidosis | |
|---|---|---|---|
| Symptoms | Older adult with gradual shortness of breath and dry cough | Gradual shortness of breath and dry cough, fatigue, skin tightening, Raynaud’s phenomenon, reflux, dysphagia | Asymptomatic or with gradual shortness of breath and cough, fatigue, palpitations, joint pain, eye and skin involvement |
| Signs | Crackles at lung bases and digital clubbing | Crackles, skin thickening and joint swelling, telangiectasias | None or crackles, skin findings, joint swelling, lymphadenopathy |
| Exposures | Tobacco smoke | Mostly unknown | Mostly unknown |
| HRCT |
| UIP or NSIP pattern, dilated esophagus, pulmonary vascular dilation | Mediastinal/hilar lymphadenopathy, reticulonodular peribronchiovascular involvement |
| Histopathology | UIP pattern (fibroblastic foci, honeycombing, spatial heterogeneity) | NSIP pattern with occasional UIP features | Non-caseating granuloma |
| Clinical course | 3–5 year survival: 50% | 10-year survival: 70%–80% | Overall good survival |
Computed tomography scans in a patient with systemic sclerosis:
Image: “Systemic sclerosis” by Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan. License: CC BY 2.0
(A) Interstitial lung disease was observed in lower lobes in a 47-year-old patient.
(B) Squamous cell lung cancer occurred in the area of interstitial lung disease in a 50-year-old patient.
Patient with sarcoidosis: (a). Chest radiograph showing massive hilar and mediastinal lymphadenopathy; (b) thoracic CT scan showing diffuse nodular infiltration of the lung interstitium. Neither of these patients complained of cough.
Image: “Chest radiograph” by College of Medicine, Swansea University, Swansea, Wales, UK. License: CC BY 2.0
Complications
- Acute exacerbations of IIPs:
- Accelerated phase of lung injury in a patient with an underlying ILD
- Acute onset (< 30 days) of respiratory distress and hypoxemia more severe than what was previously experienced by the underlying ILD and not explained by other causes (e.g., pneumonia, heart failure)
- Most commonly described in IPF
- Lung HRCT shows a change in the pattern previously observed due to the underlying ILD with patchy bilateral ground-glass opacities and consolidation in dependent regions.
- Histopathology shows diffuse alveolar damage.
- Treatment is supportive as no proven therapy exists; lung transplantation may provide cure.
- Mortality rate > 85%
- Pulmonary hypertension
- Pneumonia
- Ischemic heart disease
- Thromboembolic disease
- Lung cancer
Differential Diagnosis
- Cardiovascular disease (e.g., heart failure)
- Diffuse infections (e.g., pneumocystis pneumonia)
- Malignancy (e.g., bronchoalveolar cell carcinoma):
- Note that ILDs such as COP may occur secondary to dermatomyositis and malignancy; however, lung malignancies such as bronchoalveolar cell carcinoma can mimic the symptoms and signs of ILD.
References
- Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2018.
- King TE, Raj R. Role of lung biopsy in the diagnosis of interstitial lung disease, in UpToDate Evidence-Based Medicine. Retrieved on August 18, 2020, from https://www.uptodate.com/contents/role-of-lung-biopsy-in-the-diagnosis-of-interstitial-lung-disease?search=interstitial-lung-disease&topicRef=4310&source=see_link#H4256910517
