Further, germ line mutations in the genes encoding telomerase reverse transcriptase (hTERT) and telomerase RNA (hTR) were implicated in dyskeratosis congenita, a rare hereditary disorder associated with pulmonary fibrosis and aplastic anemia [50]

Further, germ line mutations in the genes encoding telomerase reverse transcriptase (hTERT) and telomerase RNA (hTR) were implicated in dyskeratosis congenita, a rare hereditary disorder associated with pulmonary fibrosis and aplastic anemia [50]. BI8622 may be indolent, spanning 5 years in some patients. Therapy has not been proven to alter the course of the disease or influence mortality, but recent studies with pirfenidone and tyrosine kinase inhibitors are promising. Lung transplantation is the best therapeutic option, but is limited to selected patients with severe, life-threatening disease and no contraindications to transplant. of UIP [1C4], but UIP pattern can also be found in other diseases (e.g., connective tissue disease (CTD), asbestosis, diverse occupational, environmental, or drug exposures) [1, 5]. Thus, the diagnosis of IPF can be established only when these and other alternative etiologies have been excluded [1]. IPF is the most common of the idiopathic interstitial pneumonias (IIPs), constituting 47C71% of cases [2, 6]. Other IIPs (e.g., respiratory bronchiolitis interstitial lung disease (RBILD), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), lymphoid interstitial pneumonia (LIP), nonspecific interstitial pneumonia (NSIP), and BI8622 cryptogenic organizing pneumonia (COP)) are distinct entities, with marked differences in prognosis and responsiveness to therapy [1, 3, 4]. These entities are discussed elsewhere in this book. In this review, we restrict our discussion to idiopathic UIP. A diagnosis of LRP2 IPF requires the demonstration of UIP by surgical lung biopsy (SLB) unless the HRCT features are classified as definite according to the recently published ATS/ERS/JRS/ALAT guidelines on IPF [1a, 3]. Because of small sample size and disease heterogeneity, transbronchial lung biopsies or percutaneous needle biopsies are adequate to diagnose UIP [1, 3]. However, SLB is expensive and has potential morbidity, and many clinicians are reluctant to recommend SLB for patients with suspected IPF. In clinical practice, SLB is performed in 30% of patients with IPF [2, 7]. Currently, many clinicians rely upon HRCT to corroborate the diagnosis of UIP [1, 8, 9]. SLBs are performed primarily in patients manifesting atypical or indeterminate patterns on CT [8, 10, 11]. What Are the Characteristic Histopathological Features of UIP? The cardinal histopathological findings of UIP include: geographic and temporal heterogeneity, alternating zones of normal and abnormal lung, predilection for peripheral (subpleural) and basilar regions, fibroblastic foci (aggregates of proliferating fibroblasts and myofibroblasts), excessive collagen and extracellular matrix (ECM), honeycomb change (HC) [3] (Table 10.1). Additional features include: smooth muscle hypertrophy, metaplasia and hyperplasia of type II pneumocytes, destroyed and disrupted alveolar architecture, traction bronchiectasis and bronchioloectasis, secondary pulmonary hypertensive changes [3]. Histopathological features of UIP are discussed by Drs. Colby and Leslie elsewhere BI8622 in this book and will not be further addressed here. Table 10.1 Histopathology of usual interstitial pneumonia IPF, we obtain serologies for CTD [e.g., ANA and antibodies to SSA, SSB, Scl-70 (scleroderma), Sm, RNP, Jo-1, double stranded DNA] [5, 12, 20] and hypersensitivity pneumonitis (HP) to rule out those disorders as treatment and prognosis may differ from IPF. Elevations of the glycoprotein KL-6 [21] and lung surfactant proteins (SP)-A and -D [22] have been noted in serum and bronchoalveolar lavage fluid (BALF) in patients with IPF, and may have prognostic value. These assays are available in only a few research laboratories, and additional studies are required to assess their specificity and clinical role. Clinical Course and Prognosis The clinical course of IPF is heterogeneous, but most patients worsen gradually (over months to years) [2]. Mean survival from the onset of symptoms is 3C5 years [2, 6, 8, 23C25]. However, the course is highly variable, and some patients remain stable for years [2, 6, 26]. In others, the course is rapid, with fatal respiratory failure evolving over a few months [27]. Additionally, some patients have gradual progression over years, followed by acute exacerbations, associated with abrupt and often fatal hypoxemic respiratory failure [26, 28]. Spontaneous remissions do not occur [2, 6]. Ten-year survival is less than 15% [2, 6, 23, 24, 29, 30]. The major cause of death is respiratory failure [31, 32]. Surveys of IPF patients in the UK and USA noted BI8622 that progression of lung disease accounted for 72% [32] and 60% [33] of deaths, respectively. Other causes include pulmonary embolism [31], cardiac failure, cerebrovascular incidents (primarily in the elderly), and lung malignancy [31, 34]. Lung malignancy happens in 4C13% of individuals with IPF [2, 34]. The risk is definitely higher in smokers, but the heightened risk of lung malignancy is not solely due to the effects of cigarette smoking [34]. Acute Exacerbations of IPF A subset of individuals with IPF develop an accelerated program often as a terminal event, with features of diffuse alveolar damage (DAD) or organizing pneumonia on lung. BI8622