Annals of the American Thoracic Society
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In the past five decades, alpha-1 antitrypsin deficiency has been the only known genetic cause of emphysema, yet it explains the genetics in only 1-2% of severe cases. Recently, mutations in telomerase genes were found to induce susceptibility to young-onset, severe, and familial emphysema at a frequency comparable to that of alpha-1 antitrypsin deficiency. Telomerase mutation carriers with emphysema report a family history of idiopathic pulmonary fibrosis, and both lung phenotypes show autosomal dominant inheritance within families. ⋯ The telomere-mediated emphysema phenotype appears to have clinically recognizable features that are distinct from alpha-1 antitrypsin deficiency, and patients are prone to developing short telomere syndrome comorbidities that influence clinical outcomes. In animal models, telomere dysfunction causes alveolar epithelial stem cell senescence, which is sufficient to drive lung remodeling and recruit inflammation. Here, we review the implications of these discoveries for understanding emphysema biology as well as for patient care.
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Multicenter Study
Barriers to Translation of Physical Activity into the Lung Cancer Model of Care. A Qualitative Study of Clinicians' Perspectives.
Evidence-based clinical practice guidelines recommend physical activity for people with lung cancer, however evidence has not translated into clinical practice and the majority of patients do not meet recommended activity levels. ⋯ Key barriers to implementation of the physical activity guidelines in lung cancer are diverse and include both clinician- and healthcare system-related factors. A combined approach to target a number of these factors should be used to inform research, improve clinical services, and develop policies aiming to increase physical activity and improve survivorship outcomes for patients with lung cancer.
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Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), represent a significant and increasing health burden. Current therapies are largely symptomatic, and novel therapeutic approaches are needed. Aging has emerged as a contributing factor for the development of both IPF and COPD because their prevalence increases with age, and several pathological features of these diseases resemble classical hallmarks of aging. ⋯ The developmental WNT pathway is fundamental for lung development, and altered WNT activity has been reported to contribute to the pathogenesis of CLD, in particular to COPD and IPF. Although to date only limited data on WNT signaling during lung aging exist, WNT signal regulation during aging and its effects on age-related pathologies in other organs have recently been investigated. In this review, we discuss evidence of dysregulated WNT signaling in CLD in the context of WNT signal alteration in organ aging and its potential impact on age-related cellular mechanisms, such as senescence or stem cell exhaustion.
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There is limited evidence of the effect of exposure to heat on chronic obstructive pulmonary disease (COPD) morbidity, and the interactive effect between indoor heat and air pollution has not been established. ⋯ For patients with COPD who spend the majority of their time indoors, indoor heat exposure during the warmer months represents a modifiable environmental exposure that may contribute to respiratory morbidity. In the context of climate change, adaptive strategies that include optimization of indoor environmental conditions are needed to protect this high-risk group from the adverse health effects of heat.
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Idiopathic pulmonary fibrosis (IPF) is an aging-associated, progressive, and irreversible lung disease of unknown etiology, elusive pathogenesis, and very limited therapeutic options. The hallmarks of IPF are aberrant activation of alveolar epithelial cells and accumulation of fibroblasts and myofibroblasts along with excessive production of extracellular matrix. ⋯ Also, aging seems to confer a profibrotic phenotype upon fibroblasts and to increase the severity of the fibrogenic response in non-IPF fibrotic lung disorders. Better knowledge of the pathophysiological mechanisms linking aging to IPF will advance understanding of its pathogenesis and may provide new therapeutic windows to treatment of this devastating disease.