Interstitial lung disease

Jump to navigation Jump to search

Interstitial Lung Disease

Home

Patient Information

Overview

Classification

Fibrosis lung response
Occupational lung disease
Drug-induced lung injury
Radiation-induced lung injury
Smoking related interstitial lung disease
Idiopathic interstitial pneumonia
Pulmonary alveolar proteinosis
Lymphocytic infiltrative disorders
Pulmonary lymphangioleiomyomatosis
Pulmonary hemorrhage syndromes
Interstitial lung disease associated with systemic diseases
Granulomatous lung response

Pathophysiology

Differentiating Interstitial Lung Disease from other Diseases

Laboratory Finidngs

For the WikiPatient page for this topic, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2], Anmol Pitliya, M.B.B.S. M.D.[3], Saarah T. Alkhairy, M.D.

Synonyms and keywords: Diffuse parenchymal lung disease; DPLD; ILD

Overview

Interstitial lung disease is a group of disorders involving pulmonary parenchyma. The exact pathogenesis of these disorders is not completely understood. There are multiple initiating factors that may lead to pulmonary injury. However, immunopathogenic responses of lung tissue are quite similar. The major histopathologic patterns in response to lung injury include inflammation, fibrosis and granulomatous response. Interstitial lung disease may be classified into several subtypes based on the lung response to tissue injury and the cause of injury. The underlying cause of interstitial lung disease may include factors such as toxic environmental or occupational exposure, cigarette smoking, and radiation. Interstitial lung disease may also be idiopathic.

Classification

Interstitial lung disease may be classified on the basis of lung response to tissue injury. The lung response to tissue injury may be characterized as:[1]

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interstitial lung disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lung Response:
Granulomatous
 
 
 
 
 
 
 
 
 
 
 
Lung Response:
Alveolitis,
Interstitial Inflammation,
and Fibrosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Known
 
 
 
 
 
Idiopathic (Unknown)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypersensitivity pneumonitis (organic dusts)
 
Inorganic dusts
 
Sarcoidosis
 
Lymphomatoid granulomatosis
 
Granulomatous vasculitides
 
Bronchocentric granulomatosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Beryllium
 
Silica
 
 
 
 
 
Eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome)
 
Granulomatosis with polyangiitis (Wegener's)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Known cause
 
 
 
 
 
 
 
Idiopathic (Unknown)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug-induced pulmonary toxicity
 
Occupational and environmental exposure
 
Radiation-induced lung injury
 
Aspiration pneumonia
 
Smoking-related
 
Residual of acute respiratory distress syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inhaled inorganic dust
 
Inhaled organic dusts
 
Inhaled agents other than inorganic or organic dusts
 
Desquamative interstitial pneumonia
 
Respiratory bronchiolitis–associated interstitial lung disease
 
Pulmonary Langerhans cell granulomatosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary alveolar proteinosis
 
Idiopathic interstitial pneumonias
 
Lymphocytic infiltrative disorders
(lymphocytic interstitial pneumonitis
associated with connective tissue disease)
 
Connective tissue
diseases
 
Gastrointestinal or
liver diseases
 
Inherited diseases
 
Graft-versus-host disease
 
Pulmonary hemorrhage syndromes
 
Eosinophilic
pneumonias
 
Lymphangioleiomyomatosis
 
Amyloidosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Major idiopathic interstitial pneumonias
 
Rare idiopathic interstitial pneumonias
 
Unclassifiable idiopathic interstitial pneumonias
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Idiopathic pulmonary fibrosis
• Idiopathic nonspecific interstitial pneumonia
• Respiratory bronchiolitis-interstitial lung disease
• Desquamative interstitial pneumonia
Cryptogenic organising pneumonia
• Acute interstitial pneumonia
 
• Idiopathic lymphoid interstitial pneumonia
• Idiopathic pleuroparenchymal fibroelastosis
 
 
 
 
 
Systemic lupus erythematosus
Rheumatoid arthritis
Ankylosing spondylitis
Systemic sclerosis
Sjögren syndrome
Polymyositis
Dermatomyositis
 
Crohn disease
Primary biliary cirrhosis
• Chronic active hepatitis
Ulcerative colitis
 
Tuberous sclerosis
Neurofibromatosis
Niemann-Pick disease
Gaucher disease
• Hermansky-Pudlak syndrome
 
Bone marrow transplantation
• Solid organ transplantation
 
Goodpasture syndrome
• Idiopathic pulmonary hemosiderosis
• Isolated pulmonary capillaritis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pathophysiology

  • Interstitial lung disease is a group of disorders affecting pulmonary parenchyma.
  • The exact pathogenesis of these disorders is not completely understood.
  • There are multiple initiating factors that may cause pulmonary injury. However, immunopathogenic responses of lung tissue are quite similar.
  • There are two major histopathologic patterns in response to lung injury which include:


Algorithm showing pathophysiology of Interstitial Lung Disease[2]


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tissue injury in lungs
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parenchymal injury
 
 
 
 
 
 
 
 
 
Vascular injury
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mast cells in lungs in response to tissue injury
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LPA6, LPA2, and LPA4 receptors[3]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decreased sFRP-1 (secreted frizzled-related protein 1) in fibroblasts[4]
 
Secretes tryptase
 
Transforming growth factor-β (TGF-β)[5]
 
 
 
 
Insulin-like growth factor (IGF) signalling[4]
 
 
 
 
 
 
 
Reduced expression of angiogenic factors,
vascular endothelial growth factor (VEGF)[6]
 
Elevation of angiostatic factors,
pigment epithelium-derived factor[7]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wnt/β-catenin signalling pathway[8][9]
 
PAR-2/protein kinase (PK)C-α/Raf-1/p44/42 signaling pathway[10]
 
Upregulation of Egr-1 (early growth response protein 1)[11]
 
IGF-binding protein 5 (IGFBP-5)[12]
 
 
 
IGF-binding protein 3 (IGFBP-3)
 
 
 
 
 
 
 
Loss of endothelial barrier function
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dysregulation of repair in lung tissue and activation of fibroblasts[13]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Regulates transforming growth factor-β (TGF-β)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induction of syndecan-2 (SDC2)[14]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activation,proliferation, and migration of fibroblast to the site of injury
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibroblasts
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Altered PTEN (phosphatase and tensin homologue)/Akt axis
 
 
 
 
Acquire contractile stress fibres
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inactivates Fox (forkhead box) O3a[15]
 
 
 
 
Protomyofibroblast, composed of cytoplasmic actins
 
Pleural mesothelial cells (PMCs)[16][17]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Downregulation of caveolin-1 (cav-1) and Fas expression[18]
 
 
 
 
De novo expression of α-smooth muscle actin (α-SMA)
 
TGF-β1-dependent mesothelial–mesenchymal transition
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibroblast resistant to apoptosis[19]
 
 
 
 
 
 
Myofibroblasts[20]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Different ranges of contractions mediated by RhoA/Rho-associated kinase
 
 
Changes in intracellular calcium concentrations
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitement of fibrocytes in lungs
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lock step mechanism of cyclic and contractile events[21]
 
 
 
 
 
 
 
 
 
T-helper cell type 2 on site of injury[22][23]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upregulation of C-X-C chemokine receptor type 4 (CXCR4)
on fibrocytes and its ligand
CXCL12 (stromal cell-derived factor 1)[24]
 
 
 
 
 
Excess extracellular matrix production
 
 
 
 
 
Exerting traction force
 
 
 
 
 
 
 
 
 
Interleukin-13
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Migration of fibrocytes to the site of injury[25]
 
 
 
 
 
Tissue remodelling[26]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alternate pathway activation of macrophages[27]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lung Fibrosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Differentiating Interstitial Lung Disease from other Diseases

To review the complete differential diagnosis of dyspnea, click here.

To review the complete differential diagnosis of hemoptysis, click here.

To review the complete differential diagnosis of restrictive lung disease, click here.

Abbreviations: ABG: Arterial blood gas, BAL: Bronchoalveolar lavage, ESR: Erythrocyte sedimentation rate, CRP: C–reactive protein, FVC: Forced vital capacity, RV: Residual volume, FEV1: Forced expiratory volume during the 1st second, DLCO: Diffusing capacity of the lungs for carbon monoxide, O2: Oxygen, TLC: Total lung capacity, PaO2: Arterial partial pressure of oxygen, FiO2: Fraction of inspired oxygen, LDH: Lactate dehydrogenase, CEA: Carcinoembryonic antigen, Anti-GBM antibody: Anti-glomerular basement membrane antibody, A−a gradient: Alveolar-arterial gradient, PAS: Periodic acid-Schiff stain, LAM: Lymphangiomyomatosis, IgE: Immunoglobulin E, ANCA: Anti-neutrophil cytoplasmic antibody, RBC: Red blood cell, ACE: Angiotensin-converting enzyme

Disease Clinical manifestation Investigations
History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Idiopathic pulmonary fibrosis[28] Chronic 60−70 years old Men + + ± + Dry + + + +
  • Bibasilar, peripheral reticular abnormalities
  • Focal honeycomb cyst formation
  • Traction bronchiectasis
  • Diagnosis of exclusion 
  • Lung biopsy
Idiopathic nonspecific interstitial pneumonia[29] Acute/Chronic 50−60 years old Female + + + + + + ±
  • Normal
  • Nonspecific
  • Lung biopsy and multidisciplinary approach
Cryptogenic organizing pneumonia[30] Acute/subacute 50−60 years old Both ± + Dry
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Acute interstitial pneumonia (Hamman−Rich syndrome)[31] Acute 50−60 years old Both + + +
  • N/A
Lymphocytic interstitial pneumonia[32] Subacute 30−40 years old Female ± + + + + +
Respiratory bronchiolitis−interstitial lung disease[33] Subacute 30−40 years old Both + + Dry +
  • Inspiratory high−pitched rhonchi
  • Fine, bibasilar end−inspiratory crackles
  • Nonspecific 
  • Diffuse or patchy ground glass opacities in a mosaic pattern 
  • Fine nodules 
  • Air trapping
  • Clinical evaluation and investigations
Desquamative interstitial pneumonia[34][35] Chronic 40−50 years old Both + + Dry +
  • Fine, bibasilar end−inspiratory crackles
  • Nonspecific 
  • Ground glass opacities without the peripheral reticular and reticulonodular opacities
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Pulmonary Langerhans cell granulomatosis[36] Chronic 20−40 years old Both + + ± Dry + +
  • Unremarkable
  • Nonspecific 
  • Normal
Pulmonary alveolar proteinosis[37][38] Acute/chronic 40−50 years old Male + + + + + + + +
  • Bbilateral perihilar and basilar alveolar opacities without air−bronchograms
  • "Bat wing" distribution
  • Intralobular thickening
  • Diffuse ground−glass opacities
Pulmonary lymphangioleiomyomatosis[39] Acute/chronic 30−40 years old Female + + + Bloody + + +
Eosinophilic pneumonia[40] Acute/chronic 20−40 years old Male + Dry + + +
  • Clinical evaluation and investigations
Hypersensitivity pneumonitis[41] Acute/subacute/chronic 40−60 years old Both ± + + Dry/productive + + + +
  • Centrilobular ground−glass or nodular opacities of mid−to−upper zone 
  • Air−trapping
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Occupational lung disease[42] Chronic Elderly Male + + + ± + + + + Peripheral/central +
  • Mineral dust +
  • History of environmental exposure and imaging
  • Lung biopsy not required
Radiation−induced lung injury[43] Subacute/chronic Any age Both + + Dry + + + +
  • Nonspecific
  • History of irradiation and clinical presentation
Pulmonary hemorrhage syndromes Goodpasture syndrome[44] Chronic All ages Male + ± ± Bloody ±
  • Pulmonary infiltrates
  • Normal
  • NA
Idiopathic pulmonary hemosiderosis[45] Acute/subacute/chronic Children − 10 years old Both + ± + Bloody + +
  • O2
  • ↓ CO2
  • Clinical evaluation and investigations
Isolated pulmonary capillaritis[46] Chronic 40−60 years old Both + ± + Bloody + + +
  • Diagnosis of exclusion
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Sarcoidosis[47] Acute/subacute/chronic 20−40 years old Female + ± ± + + ± +
  • Clinical evaluation and investigations
Granulomatous vasculitides Granulomatosis with polyangiitis (Wegener)[48] Chronic Elderly Both + + + + ±
  • Alveolar hemorrhage
Eosinophilic granulomatosis with polyangiitis (Churg Strauss)[49] Chronic 40−50 years old Both + + +
  • Areas of parenchymal opacification
  • Mixed interstitial patchy alveolar opacities
  • Normal
Bronchocentric granulomatosis[50] Chronic 30−70 years old Both ± ± + ±
  • Normal
Pulmonary lymphomatoid granulomatosis[51] Chronic 30−50 years old Male + + + +
  • Normal
  • Mid to lower zone multiple poorly defined nodules
  • Diffuse reticular abnormalities
  • Normal
  • Normal
Amyloidosis[52][53] Subacute/chronic 50−70 years old Male + Bloody +
  • Congophilia with apple−green birefringence under polarized light
  • Normal
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG

Laboratory Finidngs

There are multiple laboratory tests that may be helpful to ascertain or rule out the diagnosis of interstitial lung disease.

Condition Disease Investigation
All patients with suspicious interstitial lung disease Complete blood count and differential
Liver function tests Alanine aminotransferase (ALT, SGPT)
Aspartate aminotransferase (AST, SGOT)
Alkaline phosphatase
Renal function tests Urinalysis
Blood urea nitrogen (BUN)
Creatinine (Cr)
Suspicious of systemic rheumatic disease RA Serology Anti−cyclic citrullinated peptide (Anti-CCP)
SLE Serology Anti−double stranded DNA antibodies (Anti-dsDNA antibody)
Amyopathic dermatomyositis Serology Anti-melanoma differentiation-associated gene 5 (MDA-5)
Nonspecific Serology Antinuclear antibody (ANA)
Serology Rheumatoid factor (RF)
Serology Anti-neutrophil cytoplasmic antibody (ANCA)
Enzyme Creatine kinase (CK), aldolase
Mechanic hands Myositis Myositis−associated antibodies Anti-tRNA synthetases Jo-1
Anti-tRNA synthetases PL-7
Anti-tRNA synthetases PL-12
Sicca features or positive anti−extractable nuclear antigen (ENA) Sjögren’s syndrome Serology Anti-RO (SS−A)
Serology Anti-La (SS−B)
Mixed connective tissue disease  Serology Anti-ribonucleoprotein (RNP)
IgG4-related disease Serology Serum IgG4
Severe GERD or sclerodactyly Limited systemic scleroderma Serology Anti-centromere
Systemic scleroderma Serology Anti-topoisomerase I (anti-Scl-70)
Dyspnea Heart failure Enzyme Brain natriuretic peptide (BNP)
Pulmonary hypertension N-terminal proBNP (NT-proBNP)
Anemia and/or hemoptysis Coagulopathies Coagulation studies
Goodpasture syndrome Serology Anti−glomerular basement membrane (GBM) antibodies
Antiphospholipid syndrome Serology Antiphospholipid antibodies
Idiopathic pulmonary hemosiderosis Serology Serum IgA endomysial or tissue transglutaminase antibodies 
Mediastinal lymphadenopathy Multiple myeloma Serum protein electrophoresis
Beryllium exposure Berylliosis Peripheral blood beryllium lymphocyte proliferation test
Risk factors for HIV HIV ELISA
Western blot test

Occupational Lung Disease

For more information about occupational lung disease, click here.

Drug-induced lung injury

More than 600 medications have pulmonary toxicity and may cause lung injury.[55]

Drug−induced lung injury
Antimicrobial Agents Anti−Inflammatory Agents Biological Agents Cardiovascular Agents Immunomodulator agents Antineoplastic agents Miscellaneous

Radiation-induced Lung Injury

Radiation has been considered as one of the causes of lung injury. About 5 to 15% of patients receiving radiation therapy may present with pulmonary symptoms.[71]

Smoking related Interstitial Lung Disease

Cigarette smoking may cause various adverse effects on pulmonary tissue.[74][75][76]

Idiopathic Interstitial Pneumonia

The idiopathic interstitial pneumonias (IIP) are a broad range of interstitial lung diseases of unknown etiology.[77][78][79][80][81][82]

For more information about Idiopathic interstitial pneumonia, click here.

For more information about idiopathic pulmonary fibrosis, click here.

For more information about Cryptogenic organizing pneumonia, click here.

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare lung disease that is characterized by the intra-alveolar accumulation of surfactant phospholipid and apoproteins.[83][84]

For more information about pulmonary alveolar proteinosis, click here.

Lymphocytic Infiltrative Disorders

Lymphocytic infiltrative disorders might cause interstitial lung disease in mostly HIV positive children.[85][86]

  • The etiology of lymphocytic infiltrative disorders is unknown. However, there is an evidence of infectious cause such as EBV in HIV positive patients.
  • The two main manifestations of lymphocytic infiltrative disorders include:

For more information about lymphocytic interstitial pneumonitis, click here.

Pulmonary Lymphangioleiomyomatosis

Lymphangiomyocytosis (LAM) is defined as a multifocal neoplasm with differentiation of the perivascular epithelioid cell that involves multiple organs.[87]

For more information about pulmonary lymphangioleiomyomatosis, click here.

Pulmonary Hemorrhage Syndromes

Pulmonary hemorrhage syndromes might cause interstitial lung disease.

  • Several pulmonary hemorrhage syndromes that affect the lung parenchyma and eventually lead to pulmonary fibrosis. Some of these are as follows:

Interstitial Lung Disease Associated with Systemic Diseases

Interstitial lung disease associated with connective tissue diseases

Interstitial lung disease associated with inherited diseases

Interstitial lung disease associated with gastrointestinal or liver diseases

Interstitial lung disease associated with graft−versus−host disease

Granulomatous Lung Response

For more information about hypersensitivity pneumonitis, click here.

References

  1. Kasper, Dennis (2015). "315: Interstitial Lung Diseases". In Talmadge, E. King, Jr. Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 0071802150.
  2. Bagnato G, Harari S (2015). "Cellular interactions in the pathogenesis of interstitial lung diseases". Eur Respir Rev. 24 (135): 102–14. doi:10.1183/09059180.00003214. PMID 25726561.
  3. Ren Y, Guo L, Tang X, Apparsundaram S, Kitson C, Deguzman J; et al. (2013). "Comparing the differential effects of LPA on the barrier function of human pulmonary endothelial cells". Microvasc Res. 85: 59–67. doi:10.1016/j.mvr.2012.10.004. PMID 23084965.
  4. 4.0 4.1 Hsu E, Shi H, Jordan RM, Lyons-Weiler J, Pilewski JM, Feghali-Bostwick CA (2011). "Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension". Arthritis Rheum. 63 (3): 783–94. doi:10.1002/art.30159. PMC 3139818. PMID 21360508.
  5. Andersson CK, Mori M, Bjermer L, Löfdahl CG, Erjefält JS (2010). "Alterations in lung mast cell populations in patients with chronic obstructive pulmonary disease". Am J Respir Crit Care Med. 181 (3): 206–17. doi:10.1164/rccm.200906-0932OC. PMID 19926870.
  6. Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M; et al. (2004). "Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis". Am J Respir Crit Care Med. 169 (11): 1203–8. doi:10.1164/rccm.200308-1111OC. PMID 14754760.
  7. Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW; et al. (2004). "Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis". Am J Respir Crit Care Med. 170 (3): 242–51. doi:10.1164/rccm.200308-1151OC. PMID 15117744.
  8. Königshoff M, Balsara N, Pfaff EM, Kramer M, Chrobak I, Seeger W; et al. (2008). "Functional Wnt signaling is increased in idiopathic pulmonary fibrosis". PLoS One. 3 (5): e2142. doi:10.1371/journal.pone.0002142. PMC 2374879. PMID 18478089.
  9. Lam AP, Flozak AS, Russell S, Wei J, Jain M, Mutlu GM; et al. (2011). "Nuclear β-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation". Am J Respir Cell Mol Biol. 45 (5): 915–22. doi:10.1165/rcmb.2010-0113OC. PMC 3262680. PMID 21454805.
  10. Wygrecka M, Dahal BK, Kosanovic D, Petersen F, Taborski B, von Gerlach S; et al. (2013). "Mast cells and fibroblasts work in concert to aggravate pulmonary fibrosis: role of transmembrane SCF and the PAR-2/PKC-α/Raf-1/p44/42 signaling pathway". Am J Pathol. 182 (6): 2094–108. doi:10.1016/j.ajpath.2013.02.013. PMID 23562441.
  11. Yasuoka H, Hsu E, Ruiz XD, Steinman RA, Choi AM, Feghali-Bostwick CA (2009). "The fibrotic phenotype induced by IGFBP-5 is regulated by MAPK activation and egr-1-dependent and -independent mechanisms". Am J Pathol. 175 (2): 605–15. doi:10.2353/ajpath.2009.080991. PMC 2716960. PMID 19628764.
  12. Bhattacharyya S, Wu M, Fang F, Tourtellotte W, Feghali-Bostwick C, Varga J (2011). "Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy". Matrix Biol. 30 (4): 235–42. doi:10.1016/j.matbio.2011.03.005. PMC 3135176. PMID 21511034.
  13. Sun Z, Gong X, Zhu H, Wang C, Xu X, Cui D; et al. (2014). "Inhibition of Wnt/β-catenin signaling promotes engraftment of mesenchymal stem cells to repair lung injury". J Cell Physiol. 229 (2): 213–24. doi:10.1002/jcp.24436. PMID 23881674.
  14. Ruiz XD, Mlakar LR, Yamaguchi Y, Su Y, Larregina AT, Pilewski JM; et al. (2012). "Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis". PLoS One. 7 (8): e43049. doi:10.1371/journal.pone.0043049. PMC 3416749. PMID 22900087.
  15. Nho RS, Peterson M, Hergert P, Henke CA (2013). "FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas". PLoS One. 8 (4): e61017. doi:10.1371/journal.pone.0061017. PMC 3620276. PMID 23580232.
  16. Mubarak KK, Montes-Worboys A, Regev D, Nasreen N, Mohammed KA, Faruqi I; et al. (2012). "Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis". Eur Respir J. 39 (1): 133–40. doi:10.1183/09031936.00141010. PMID 21737551.
  17. Nasreen N, Mohammed KA, Mubarak KK, Baz MA, Akindipe OA, Fernandez-Bussy S; et al. (2009). "Pleural mesothelial cell transformation into myofibroblasts and haptotactic migration in response to TGF-beta1 in vitro". Am J Physiol Lung Cell Mol Physiol. 297 (1): L115–24. doi:10.1152/ajplung.90587.2008. PMC 2711818. PMID 19411308.
  18. Del Galdo F, Sotgia F, de Almeida CJ, Jasmin JF, Musick M, Lisanti MP; et al. (2008). "Decreased expression of caveolin 1 in patients with systemic sclerosis: crucial role in the pathogenesis of tissue fibrosis". Arthritis Rheum. 58 (9): 2854–65. doi:10.1002/art.23791. PMC 2770094. PMID 18759267.
  19. Thannickal VJ, Horowitz JC (2006). "Evolving concepts of apoptosis in idiopathic pulmonary fibrosis". Proc Am Thorac Soc. 3 (4): 350–6. doi:10.1513/pats.200601-001TK. PMC 2231523. PMID 16738200.
  20. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002). "Myofibroblasts and mechano-regulation of connective tissue remodelling". Nat Rev Mol Cell Biol. 3 (5): 349–63. doi:10.1038/nrm809. PMID 11988769.
  21. Castella LF, Buscemi L, Godbout C, Meister JJ, Hinz B (2010). "A new lock-step mechanism of matrix remodelling based on subcellular contractile events". J Cell Sci. 123 (Pt 10): 1751–60. doi:10.1242/jcs.066795. PMID 20427321.
  22. Capelli A, Di Stefano A, Gnemmi I, Donner CF (2005). "CCR5 expression and CC chemokine levels in idiopathic pulmonary fibrosis". Eur Respir J. 25 (4): 701–7. doi:10.1183/09031936.05.00082604. PMID 15802346.
  23. Belperio JA, Dy M, Murray L, Burdick MD, Xue YY, Strieter RM; et al. (2004). "The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis". J Immunol. 173 (7): 4692–8. PMID 15383605.
  24. Andersson-Sjöland A, de Alba CG, Nihlberg K, Becerril C, Ramírez R, Pardo A; et al. (2008). "Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis". Int J Biochem Cell Biol. 40 (10): 2129–40. doi:10.1016/j.biocel.2008.02.012. PMID 18374622.
  25. Moore BB, Kolodsick JE, Thannickal VJ, Cooke K, Moore TA, Hogaboam C; et al. (2005). "CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury". Am J Pathol. 166 (3): 675–84. doi:10.1016/S0002-9440(10)62289-4. PMC 1780139. PMID 15743780.
  26. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007). "The myofibroblast: one function, multiple origins". Am J Pathol. 170 (6): 1807–16. doi:10.2353/ajpath.2007.070112. PMC 1899462. PMID 17525249.
  27. Lohmann-Matthes ML, Steinmüller C, Franke-Ullmann G (1994). "Pulmonary macrophages". Eur Respir J. 7 (9): 1678–89. PMID 7995399.
  28. Poletti, Venerino; Ravaglia, Claudia; Buccioli, Matteo; Tantalocco, Paola; Piciucchi, Sara; Dubini, Alessandra; Carloni, Angelo; Chilosi, Marco; Tomassetti, Sara (2013). "Idiopathic Pulmonary Fibrosis: Diagnosis and Prognostic Evaluation". Respiration. 86 (1): 5–12. doi:10.1159/000353580. ISSN 1423-0356.
  29. Travis, William D.; Hunninghake, Gary; King, Talmadge E.; Lynch, David A.; Colby, Thomas V.; Galvin, Jeffrey R.; Brown, Kevin K.; Chung, Man Pyo; Cordier, Jean-François; du Bois, Roland M.; Flaherty, Kevin R.; Franks, Teri J.; Hansell, David M.; Hartman, Thomas E.; Kazerooni, Ella A.; Kim, Dong Soon; Kitaichi, Masanori; Koyama, Takashi; Martinez, Fernando J.; Nagai, Sonoko; Midthun, David E.; Müller, Nestor L.; Nicholson, Andrew G.; Raghu, Ganesh; Selman, Moisés; Wells, Athol (2008). "Idiopathic Nonspecific Interstitial Pneumonia". American Journal of Respiratory and Critical Care Medicine. 177 (12): 1338–1347. doi:10.1164/rccm.200611-1685OC. ISSN 1073-449X.
  30. Mehrian, P.; Doroudinia, A.; Rashti, A.; Aloosh, O.; Dorudinia, A. (2017). "High-resolution computed tomography findings in chronic eosinophilic vs. cryptogenic organising pneumonia". The International Journal of Tuberculosis and Lung Disease. 21 (11): 1181–1186. doi:10.5588/ijtld.16.0723. ISSN 1027-3719.
  31. Parambil, Joseph; Mukhopadhyay, Sanjay (2012). "Acute Interstitial Pneumonia (AIP): Relationship to Hamman-Rich Syndrome, Diffuse Alveolar Damage (DAD), and Acute Respiratory Distress Syndrome (ARDS)". Seminars in Respiratory and Critical Care Medicine. 33 (05): 476–485. doi:10.1055/s-0032-1325158. ISSN 1069-3424.
  32. Panchabhai, Tanmay S.; Farver, Carol; Highland, Kristin B. (2016). "Lymphocytic Interstitial Pneumonia". Clinics in Chest Medicine. 37 (3): 463–474. doi:10.1016/j.ccm.2016.04.009. ISSN 0272-5231.
  33. Sieminska, Alicja; Kuziemski, Krzysztof (2014). "Respiratory bronchiolitis-interstitial lung disease". Orphanet Journal of Rare Diseases. 9 (1). doi:10.1186/s13023-014-0106-8. ISSN 1750-1172.
  34. Ryu, Jay H.; Myers, Jeffrey L.; Capizzi, Stephen A.; Douglas, William W.; Vassallo, Robert; Decker, Paul A. (2005). "Desquamative Interstitial Pneumonia and Respiratory Bronchiolitis-Associated Interstitial Lung Disease". Chest. 127 (1): 178–184. doi:10.1378/chest.127.1.178. ISSN 0012-3692.
  35. Craig, P J; Wells, A U; Doffman, S; Rassl, D; Colby, T V; Hansell, D M; du Bois, R M; Nicholson, A G (2004). "Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking". Histopathology. 45 (3): 275–282. doi:10.1111/j.1365-2559.2004.01921.x. ISSN 0309-0167.
  36. Blakley, Matthew P.; Dutcher, Janice P.; Wiernik, Peter H. (2018). "Pulmonary Langerhans cell histiocytosis, acute myeloid leukemia, and myelofibrosis in a large family and review of the literature". Leukemia Research. 67: 39–44. doi:10.1016/j.leukres.2018.01.011. ISSN 0145-2126.
  37. Carrington JM, Hershberger DM. PMID 29493933. Missing or empty |title= (help)
  38. Kiani, Arda; Parsa, Tahereh; Adimi Naghan, Parisa; Dutau, Hervé; Razavi, Fatemeh; Farzanegan, Behrooz; Pourabdollah Tootkaboni, Mahsa; Abedini, Atefeh (2018). "An eleven-year retrospective cross-sectional study on pulmonary alveolar proteinosis". Advances in Respiratory Medicine. 86 (1): 7–12. doi:10.5603/ARM.2018.0003. ISSN 2543-6031.
  39. Xu, Kai-Feng; Lo, Bee Hong (2014). "Lymphangioleiomyomatosis: differential diagnosis and optimal management". Therapeutics and Clinical Risk Management: 691. doi:10.2147/TCRM.S50784. ISSN 1178-203X.
  40. Bernheim, Adam; McLoud, Theresa (2017). "A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases". American Journal of Roentgenology. 208 (5): 1002–1010. doi:10.2214/AJR.16.17315. ISSN 0361-803X.
  41. Miller, Ross; Allen, Timothy Craig; Barrios, Roberto J.; Beasley, Mary Beth; Burke, Louise; Cagle, Philip T.; Capelozzi, Vera Luiza; Ge, Yimin; Hariri, Lida P.; Kerr, Keith M.; Khoor, Andras; Larsen, Brandon T.; Mark, Eugene J.; Matsubara, Osamu; Mehrad, Mitra; Mino-Kenudson, Mari; Raparia, Kirtee; Roden, Anja Christiane; Russell, Prudence; Schneider, Frank; Sholl, Lynette M.; Smith, Maxwell Lawrence (2018). "Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society". Archives of Pathology & Laboratory Medicine. 142 (1): 120–126. doi:10.5858/arpa.2017-0138-SA. ISSN 0003-9985.
  42. Sirajuddin, Arlene; Kanne, Jeffrey P. (2009). "Occupational Lung Disease". Journal of Thoracic Imaging. 24 (4): 310–320. doi:10.1097/RTI.0b013e3181c1a9b3. ISSN 0883-5993.
  43. 43.0 43.1 Giridhar P, Mallick S, Rath GK, Julka PK (2015). "Radiation induced lung injury: prediction, assessment and management". Asian Pac. J. Cancer Prev. 16 (7): 2613–7. PMID 25854336.
  44. DeVrieze BW, Hurley JA. PMID 29083697. Missing or empty |title= (help)
  45. Khorashadi, L.; Wu, C.C.; Betancourt, S.L.; Carter, B.W. (2015). "Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient". Clinical Radiology. 70 (5): 459–465. doi:10.1016/j.crad.2014.11.007. ISSN 0009-9260.
  46. Thompson, Gwen; Klecka, Mary; Roden, Anja C.; Specks, Ulrich; Cartin-Ceba, Rodrigo (2016). "Biopsy-proven pulmonary capillaritis: A retrospective study of aetiologies including an in-depth look at isolated pulmonary capillaritis". Respirology. 21 (4): 734–738. doi:10.1111/resp.12738. ISSN 1323-7799.
  47. Li, Cheng-Wei; Tao, Ru-Jia; Zou, Dan-Feng; Li, Man-Hui; Xu, Xin; Cao, Wei-Jun (2018). "Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China". BMJ Open. 8 (2): e018865. doi:10.1136/bmjopen-2017-018865. ISSN 2044-6055.
  48. Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M (June 2016). "Clinic manifestations in granulomatosis with polyangiitis". Int J Immunopathol Pharmacol. 29 (2): 151–9. doi:10.1177/0394632015617063. PMC 5806708. PMID 26684637.
  49. Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Ruoppolo G, Altissimi G, De Vincentiis M (April 2015). "Churg-Strauss syndrome". Autoimmun Rev. 14 (4): 341–8. doi:10.1016/j.autrev.2014.12.004. PMID 25500434.
  50. Myers, Jeffrey L. (1989). "Bronchocentric Granulomatosis". Chest. 96 (1): 3–4. doi:10.1378/chest.96.1.3. ISSN 0012-3692.
  51. Ankita, Grover; Shashi, Dhawan (2016). "Pulmonary Lymphomatoid Granulomatosis- a Case Report with Review of Literature". Indian Journal of Surgical Oncology. 7 (4): 484–487. doi:10.1007/s13193-016-0525-1. ISSN 0975-7651.
  52. Khoor, Andras; Colby, Thomas V. (2017). "Amyloidosis of the Lung". Archives of Pathology & Laboratory Medicine. 141 (2): 247–254. doi:10.5858/arpa.2016-0102-RA. ISSN 0003-9985.
  53. Milani, Paolo; Basset, Marco; Russo, Francesca; Foli, Andrea; Palladini, Giovanni; Merlini, Giampaolo (2017). "The lung in amyloidosis". European Respiratory Review. 26 (145): 170046. doi:10.1183/16000617.0046-2017. ISSN 0905-9180.
  54. Castranova V, Vallyathan V (2000). "Silicosis and coal workers' pneumoconiosis". Environ Health Perspect. 108 Suppl 4: 675–84. PMC 1637684. PMID 10931786.
  55. Camus, Philippe; Bonniaud, Philippe; Fanton, Annlyse; Camus, Clio; Baudaun, Nicolas; Foucher, Pascal (2004). "Drug-induced and iatrogenic infiltrative lung disease". Clinics in Chest Medicine. 25 (3): 479–519. doi:10.1016/j.ccm.2004.05.006. ISSN 0272-5231.
  56. Todd NW, Peters WP, Ost AH, Roggli VL, Piantadosi CA (May 1993). "Pulmonary drug toxicity in patients with primary breast cancer treated with high-dose combination chemotherapy and autologous bone marrow transplantation". Am. Rev. Respir. Dis. 147 (5): 1264–70. doi:10.1164/ajrccm/147.5.1264. PMID 8484641.
  57. Schwarz MI, Fontenot AP (March 2004). "Drug-induced diffuse alveolar hemorrhage syndromes and vasculitis". Clin. Chest Med. 25 (1): 133–40. doi:10.1016/S0272-5231(03)00139-4. PMID 15062605.
  58. De Vuyst P, Pfitzenmeyer P, Camus P (December 1997). "Asbestos, ergot drugs and the pleura". Eur. Respir. J. 10 (12): 2695–8. PMID 9493644.
  59. Wijnen PA, Bekers O, Drent M (September 2010). "Relationship between drug-induced interstitial lung diseases and cytochrome P450 polymorphisms". Curr Opin Pulm Med. 16 (5): 496–502. doi:10.1097/MCP.0b013e32833c06f1. PMID 20592596.
  60. Matsuno, Osamu (2012). "Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches". Respiratory Research. 13 (1): 39. doi:10.1186/1465-9921-13-39. ISSN 1465-9921.
  61. Gingo MR, George MP, Kessinger CJ, Lucht L, Rissler B, Weinman R, Slivka WA, McMahon DK, Wenzel SE, Sciurba FC, Morris A (September 2010). "Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era". Am. J. Respir. Crit. Care Med. 182 (6): 790–6. doi:10.1164/rccm.200912-1858OC. PMC 2949404. PMID 20522793.
  62. Kalaycioglu M, Kavuru M, Tuason L, Bolwell B (February 1995). "Empiric prednisone therapy for pulmonary toxic reaction after high-dose chemotherapy containing carmustine (BCNU)". Chest. 107 (2): 482–7. PMID 7842781.
  63. Schwaiblmair, Martin (2012). "Drug Induced Interstitial Lung Disease". The Open Respiratory Medicine Journal. 6 (1): 63–74. doi:10.2174/1874306401206010063. ISSN 1874-3064.
  64. Vasić NR, Milenković BA, Pešut DP, Stević RS, Jovanović DM (2014). "Drug induced lung disease--amiodarone in focus". Med. Pregl. 67 (9–10): 334–7. PMID 25546981.
  65. Wolkove N, Baltzan M (2009). "Amiodarone pulmonary toxicity". Can. Respir. J. 16 (2): 43–8. PMC 2687560. PMID 19399307.
  66. Fernández, Antonio B.; Karas, Richard H.; Alsheikh-Ali, Alawi A.; Thompson, Paul D. (2008). "Statins and Interstitial Lung Disease". Chest. 134 (4): 824–830. doi:10.1378/chest.08-0943. ISSN 0012-3692.
  67. O'Driscoll BR, Hasleton PS, Taylor PM, Poulter LW, Gattameneni HR, Woodcock AA (August 1990). "Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood". N. Engl. J. Med. 323 (6): 378–82. doi:10.1056/NEJM199008093230604. PMID 2370889.
  68. Todd NW, Peters WP, Ost AH, Roggli VL, Piantadosi CA (May 1993). "Pulmonary drug toxicity in patients with primary breast cancer treated with high-dose combination chemotherapy and autologous bone marrow transplantation". Am. Rev. Respir. Dis. 147 (5): 1264–70. doi:10.1164/ajrccm/147.5.1264. PMID 8484641.
  69. Tamura M, Saraya T, Fujiwara M, Hiraoka S, Yokoyama T, Yano K, Ishii H, Furuse J, Goya T, Takizawa H, Goto H (2013). "High-resolution computed tomography findings for patients with drug-induced pulmonary toxicity, with special reference to hypersensitivity pneumonitis-like patterns in gemcitabine-induced cases". Oncologist. 18 (4): 454–9. doi:10.1634/theoncologist.2012-0248. PMC 3639533. PMID 23404815.
  70. Drent M, Wijnen P, Bast A (2012). "Interstitial lung damage due to cocaine abuse: pathogenesis, pharmacogenomics and therapy". Curr. Med. Chem. 19 (33): 5607–11. PMID 22934773.
  71. Malaviya, Rama; Gow, Andrew J.; Francis, Mary; Abramova, Elena V.; Laskin, Jeffrey D.; Laskin, Debra L. (2015). "Radiation-Induced Lung Injury and Inflammation in Mice: Role of Inducible Nitric Oxide Synthase and Surfactant Protein D". Toxicological Sciences. 144 (1): 27–38. doi:10.1093/toxsci/kfu255. ISSN 1096-0929.
  72. Kong FM, Ten Haken R, Eisbruch A, Lawrence TS (April 2005). "Non-small cell lung cancer therapy-related pulmonary toxicity: an update on radiation pneumonitis and fibrosis". Semin. Oncol. 32 (2 Suppl 3): S42–54. PMID 16015535.
  73. Tsoutsou PG, Koukourakis MI (December 2006). "Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research". Int. J. Radiat. Oncol. Biol. Phys. 66 (5): 1281–93. doi:10.1016/j.ijrobp.2006.08.058. PMID 17126203.
  74. Nagai, Sonoko (2000). "Smoking-related interstitial lung diseases". Current Opinion in Pulmonary Medicine. 6 (5): 415–9. PMID 10958232. Unknown parameter |coauthors= ignored (help)
  75. Baumgartner, KB (1997). "Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis". American Journal of Respiratory and Critical Care Medicine. 155 (1): 242–248. PMID 9001319. Unknown parameter |coauthors= ignored (help)
  76. Kumar A, Cherian SV, Vassallo R, Yi ES, Ryu JH (December 2017). "Current Concepts in Pathogenesis, Diagnosis, and Management of Smoking-Related Interstitial Lung Diseases". Chest. doi:10.1016/j.chest.2017.11.023. PMID 29222007.
  77. Selman, Moisés (2001). "Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy". Annals of Internal Medicine. 134 (2): 136–51. Unknown parameter |coauthors= ignored (help)
  78. King, Jr., Talmadge E. (2005). "Centennial review: clinical advances in the diagnosis and therapy of the interstitial lung diseases". American Journal of Respiratory and Critical Care Medicine. 172 (3): 268–79.
  79. Flaherty, KR.; Travis, WD.; Colby, TV.; Toews, GB.; Kazerooni, EA.; Gross, BH.; Jain, A.; Strawderman, RL.; Flint, A. (2001). "Histopathologic variability in usual and nonspecific interstitial pneumonias". Am J Respir Crit Care Med. 164 (9): 1722–7. doi:10.1164/ajrccm.164.9.2103074. PMID 11719316. Unknown parameter |month= ignored (help)
  80. Cottin, V.; Donsbeck, AV.; Revel, D.; Loire, R.; Cordier, JF. (1998). "Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients". Am J Respir Crit Care Med. 158 (4): 1286–93. doi:10.1164/ajrccm.158.4.9802119. PMID 9769293. Unknown parameter |month= ignored (help)
  81. Park, CS.; Jeon, JW.; Park, SW.; Lim, GI.; Jeong, SH.; Uh, ST.; Park, JS.; Choi, DL.; Jin, SY. (1996). "Nonspecific interstitial pneumonia/fibrosis: clinical manifestations, histologic and radiologic features". Korean J Intern Med. 11 (2): 122–32. PMID 8854648. Unknown parameter |month= ignored (help)
  82. Shimizu, S.; Yoshinouchi, T.; Ohtsuki, Y.; Fujita, J.; Sugiura, Y.; Banno, S.; Yamadori, I.; Eimoto, T.; Ueda, R. (2002). "The appearance of S-100 protein-positive dendritic cells and the distribution of lymphocyte subsets in idiopathic nonspecific interstitial pneumonia". Respir Med. 96 (10): 770–6. PMID 12412975. Unknown parameter |month= ignored (help)
  83. Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED (June 2015). "Pulmonary alveolar proteinosis: time to shift?". Expert Rev Respir Med. 9 (3): 337–49. doi:10.1586/17476348.2015.1035259. PMID 25864717.
  84. Suzuki T, Trapnell BC (September 2016). "Pulmonary Alveolar Proteinosis Syndrome". Clin. Chest Med. 37 (3): 431–40. doi:10.1016/j.ccm.2016.04.006. PMID 27514590.
  85. Panchabhai TS, Farver C, Highland KB (September 2016). "Lymphocytic Interstitial Pneumonia". Clin. Chest Med. 37 (3): 463–74. doi:10.1016/j.ccm.2016.04.009. PMID 27514593.
  86. Fishback N, Koss M (September 1996). "Update on lymphoid interstitial pneumonitis". Curr Opin Pulm Med. 2 (5): 429–33. PMID 9363179.
  87. Verma AK, Joshi A, Mishra AR, Kant S, Singh A (2018). "Pulmonary lymphangioleiomyomatosis presenting as spontaneous pneumothorax treated with sirolimus - A case report". Lung India. 35 (2): 154–156. doi:10.4103/lungindia.lungindia_60_17. PMID 29487252.