| Domain | Knowledge-base summary | Suggested ontology terms |
|---|---|---|
| Scope / classification | **Idiopathic interstitial pneumonia (IIP)** is a **family of idiopathic diffuse parenchymal lung diseases**, not a single entity. **Idiopathic pulmonary fibrosis (IPF)** is one **major fibrotic subtype** within IIP. Major adult IIP subtypes commonly referenced in modern practice include IPF, idiopathic nonspecific interstitial pneumonia (iNSIP), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), respiratory bronchiolitis–ILD (RB-ILD), desquamative interstitial pneumonia (DIP), lymphoid interstitial pneumonia (LIP), and pleuroparenchymal fibroelastosis (PPFE); multidisciplinary clinico-radiologic-pathologic diagnosis is central. (pqac-00000000, pqac-00000005) | MONDO: **idiopathic interstitial pneumonia** (MONDO_0002429); EFO: **idiopathic pulmonary fibrosis** (EFO_0000768); disease labels: idiopathic NSIP, COP, AIP, RB-ILD, DIP, LIP, PPFE; imaging/pathology labels: UIP, NSIP, OP |
| Core phenotypes | Typical fibrotic IIP/IPF phenotype is **adult-onset progressive exertional dyspnea and chronic dry cough**, often with **bibasilar crackles** and **digital clubbing**; physiology usually shows a **restrictive ventilatory defect** with reduced **FVC** and **DLCO**. Clubbing is reported in roughly **25–50%** of IPF cases; cough burden can be substantial and QoL-limiting. (pqac-00000020, pqac-00000022, pqac-00000024) | HPO: **Dyspnea**, **Cough**, **Clubbing**, **Abnormal respiratory crackles**, **Restrictive ventilatory defect**, **Decreased diffusing capacity of lung for carbon monoxide** |
| Anatomy / cells | Primary site is the **lung parenchyma**, especially **distal lung/alveolar regions** with subpleural-basal predominance in UIP/IPF. Key involved cell types include **alveolar type 2 epithelial cells (AT2)**, aberrant basaloid/bronchiolized epithelial cells, **fibroblasts/myofibroblasts**, **macrophages** (including SPP1-high), endothelial cells, and other stromal/immune populations. (pqac-00000015, pqac-00000019, pqac-00000022) | UBERON: **lung**, **alveolus**, **lung interstitium**, **bronchiole**, **pleura**; CL: **alveolar type 2 epithelial cell**, **fibroblast**, **myofibroblast**, **macrophage**, **endothelial cell** |
| Genetic architecture | Genetic contribution spans **rare pathogenic variants** and **common susceptibility alleles**. Strongest common risk allele is **MUC5B promoter rs35705950**; rare high-effect variants occur in **telomere genes** (**TERT, TERC, RTEL1, PARN**) and **surfactant-related genes** (**SFTPA1, SFTPA2, SFTPC, ABCA3**). Familial pulmonary fibrosis often shows **autosomal dominant inheritance with incomplete, age-dependent penetrance** for rare telomere-pathway variants; common alleles also involve **DSP, FAM13A, TOLLIP, DPP9** and related loci. (pqac-00000007, pqac-00000008, pqac-00000012, pqac-00000014, pqac-00000006) | Genes: **MUC5B, TERT, TERC, RTEL1, PARN, SFTPA1, SFTPA2, SFTPC, ABCA3, DSP, FAM13A, TOLLIP, DPP9**; variation labels: **pathogenic/likely pathogenic variant**, **susceptibility allele**, **autosomal dominant inheritance**, **incomplete penetrance** |
| Mechanism / pathophysiology | Current model emphasizes **repetitive alveolar epithelial injury** in a genetically susceptible, aging lung, followed by **aberrant repair**, **fibroblast expansion**, **myofibroblast differentiation**, **extracellular matrix accumulation**, increasing **tissue stiffness**, and feed-forward profibrotic signaling. Core pathways include **TGF-beta**, **Wnt/beta-catenin**, **Hippo/YAP-TAZ**, **Hedgehog**, epithelial ER stress, senescence/telomere dysfunction, and immune-metabolic remodeling. Single-cell/spatial studies highlight **IR-AT2**, **aberrant basaloid cells**, **CTHRC1+ fibroblasts**, meflin+ fibroblasts, and **SPP1hi macrophages** in spatial fibrotic niches. (pqac-00000015, pqac-00000018, pqac-00000019, pqac-00000021) | GO: **fibrotic process / fibrosis**, **transforming growth factor beta signaling pathway**, **extracellular matrix organization**, **epithelial to mesenchymal transition**, **cellular senescence**, **wound healing**, **collagen fibril organization**; CL: **alveolar type 2 epithelial cell**, **fibroblast**, **myofibroblast**, **macrophage** |
| Diagnostics | Diagnosis relies on **multidisciplinary discussion** integrating exposure/autoimmune history, serology, **HRCT**, PFTs, and sometimes tissue sampling. For IPF, HRCT showing **definite/probable UIP** with exclusion of alternative causes can establish diagnosis; biopsy/cryobiopsy is considered when imaging is indeterminate. Useful biomarker candidates include **KL-6**, **SP-A/SP-D**, and **MMP-7**, though broad routine implementation remains limited. Differential diagnosis includes CTD-ILD, hypersensitivity pneumonitis, asbestosis, drug-induced ILD, and non-IPF IIP subtypes. (pqac-00000003, pqac-00000004, pqac-00000022, pqac-00000023) | Imaging/pathology labels: **usual interstitial pneumonia (UIP)**, **probable UIP**, **indeterminate for UIP**, **NSIP pattern**, **organizing pneumonia pattern**; HPO: **Abnormality of pulmonary function test**; specimen terms: **surgical lung biopsy**, **transbronchial lung cryobiopsy** |
| Treatment | **Antifibrotics** are standard for IPF: **nintedanib** and **pirfenidone** slow FVC decline and reduce progression/exacerbation risk. Nonpharmacologic management includes **pulmonary rehabilitation**, **supplemental oxygen** when indicated, symptom-focused supportive/palliative care, vaccination and comorbidity management, and **lung transplantation** for appropriate candidates. Management differs across IIP subtypes: e.g., COP is typically corticosteroid-responsive, smoking-related RB-ILD/DIP emphasize smoking cessation, and non-IPF inflammatory phenotypes may involve immunomodulation rather than primary antifibrotic therapy. (pqac-00000000, pqac-00000027, pqac-00000028, pqac-00000031) | NCIT/intervention labels: **Nintedanib**, **Pirfenidone**, **Pulmonary Rehabilitation**, **Oxygen Therapy**, **Lung Transplantation**, **Palliative Care**, **Corticosteroid Therapy**, **Smoking Cessation** |
| Models / other species | Human IIP/IPF is modeled mainly with **induced pulmonary fibrosis systems** rather than a fully faithful spontaneous animal disease. Common platforms include **bleomycin-induced fibrosis** (mouse and other species), xenograft models using human IPF fibroblasts, genetic/telomere-related models, and ex vivo/in vitro systems such as lung explants or organoid-like epithelial-fibroblast models. Naturally occurring canine pulmonary fibrosis, especially in **West Highland White Terriers**, shows similarities to human IPF but has limited utility because of low prevalence and incompletely defined pathogenesis; zoonotic transmission is not a feature. (pqac-00000032) | NCBI Taxon labels: **Homo sapiens**, **Mus musculus**, **Canis lupus familiaris**; model labels: **bleomycin-induced pulmonary fibrosis**, **xenograft model**, **genetic model**, **lung explant**, **organoid** |


*Table: This compact table organizes the key knowledge-base domains for idiopathic interstitial pneumonia, explicitly distinguishing the IIP family from IPF as a subtype. It also provides ontology-ready term suggestions to support structured disease annotation.*