alt=Pathobiology of<unk>  Despite extensive investigation, the cause of<unk>  remains unknown. The<unk>  in<unk>  has been linked to cigarette smoking, environmental factors (e.g. occupational exposure to gases, smoke, chemicals or dusts), other medical conditions including gastroesophageal reflux disease (GERD), or to genetic predisposition (familial<unk> . However, none of these is present in all people with<unk>  and therefore do not provide a completely satisfactory explanation for the disease.<unk>  is believed to be the result of an aberrant wound healing process including/involving abnormal and excessive deposition of collagen<unk>  in the pulmonary interstitium with minimal associated inflammation. Cellular senescence is suspected to be a central contributing cause, a belief which is supported by benefits seen in patients given senolytic therapy. It is hypothesized that the initial or repetitive injury in<unk>  occurs to the lung cells, called alveolar epithelial cells (AECs, pneumocytes), which line the majority of the alveolar surface. When type I AECs are damaged or lost, it is thought that type II AECs undergo proliferation to cover the exposed basement membranes. In normal repair, the hyperplastic type II AECs die and the remaining cells spread and undergo a differentiation process to become type I AECs. Under pathologic conditions and in the presence of transforming growth factor beta (TGF-β), fibroblasts accumulate in these areas of damage and differentiate into myofibroblasts that secrete collagen and other proteins. In the current classification of the pathogenesis of<unk> , it is believed that it occurs by way of the formation of a UIP (usual interstitial pneumonia) lesion, which then undergoes the aforementioned pathological condition characteristic of<unk> . Other proposed repeated injury mechanisms indicate that<unk>  may result not just from a UIP lesion, but also from NSIP and DAD (nonspecific interstitial pneumonia and diffuse alveolar damage) lesions, or a combination of several. In the past, it was thought that inflammation was the first event in initiating lung tissue scarring. Later findings showed that the development of fibroblastic foci precedes the accumulation of inflammatory cells and the consequent deposition of collagen. This pathogenetic model is indirectly supported by the clinical features of<unk> , including an insidious onset over several years, relatively infrequent acute exacerbations, and failure to respond to immunosuppressive therapy. However, it is the belief of some researchers that the disease is a multi-mechanistic one, wherein the trigger for the disease may stem from abnormalities in any number of wound healing pathways, including the inflammatory response. Such abnormalities could occur in any number of the nine implicated pathways (clotting cascade, antioxidant pathways, apoptosis, inflammatory cytokines, angiogenesis and vascular remodelling, growth factors, surfactant and matrix regulatory factors), and that through further investigation into all nine, novel therapies and approaches could be proposed on a unique or case by case basis should attempts at treating or circumventing complications in any one pathway prove unsuccessful. A number of therapies that target fibroblast activation or the synthesis of extracellular matrix are currently in early testing or are being considered for development. Familial<unk>  accounts for less than 5% of the total of patients with<unk>  and is clinically and histologically indistinguishable from sporadic<unk> . Genetic associations include mutations in pulmonary surfactant proteins A1, A2, C (SFTPA1, SFTPA2B) and mucin (MUC5B). A remarkable aspect of the MUC5B variant is its high frequency of detection, as it is found in approximately 20% of individuals with Northern and Western European ancestry and in 19% of the Framingham Heart Study population. Mutations in human telomerase genes are also associated with familial pulmonary<unk>  and in some patients with sporadic<unk>  (e.g. the TERT, TERC genes). Recently an X-linked mutation in a third telomerase-associated gene, dyskerin (DKC1), has been described in a family with<unk> .
Idiopathic pulmonary fibrosis
Sarcoidosis
Mineral dust airway disease
Hypersensitivity pneumonitis
Allergic bronchopulmonary aspergillosis
Interstitial lung disease
Rheumatoid lung disease
Idiopathic interstitial pneumonia