American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2023
Long-Term Follow-Up of Interstitial Lung Abnormality: Implication in Follow-Up Strategy and Risk Thresholds.
Rationale: The optimal follow-up computed tomography (CT) interval for detecting the progression of interstitial lung abnormality (ILA) is unknown. Objectives: To identify optimal follow-up strategies and extent thresholds on CT relevant to outcomes. Methods: This retrospective study included self-referred screening participants aged 50 years or older, including nonsmokers, who had imaging findings relevant to ILA on chest CT scans. ⋯ The extent of fibrosis on CT was an independent risk factor for ILA progression (hazard ratio, 1.12 [95% CI, 1.02-1.23]) and progression to UIP (hazard ratio, 1.39 [95% CI, 1.07-1.80]). Risk groups based on honeycombing and extent of fibrosis (1% in the whole lung or 5% per lung zone) showed significant differences in 10-year overall survival (P = 0.02). Conclusions: For individuals with initially detected ILA, follow-up CT at 3-year intervals may be appropriate to monitor radiologic progression; however, those at high risk of adverse outcomes on the basis of the quantified extent of fibrotic ILA and the presence of honeycombing may benefit from shortening the interval for follow-up scans.
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Am. J. Respir. Crit. Care Med. · Oct 2023
Restoration of Foxp3+ Regulatory T Cells by HDAC-dependent Epigenetic Modulation Plays a Pivotal Role in Resolving Pulmonary Arterial Hypertension Pathology.
Rationale: Immune dysregulation is a common feature of pulmonary arterial hypertension (PAH). Histone deacetylase (HDAC)-dependent transcriptional reprogramming epigenetically modulates immune homeostasis and is a novel disease-oriented approach in modern times. Objectives: To identify a novel functional link between HDAC and regulatory T cells (Tregs) in PAH, aiming to establish disease-modified biomarkers and therapeutic targets. ⋯ Furthermore, SAHA inhibited endothelial cytokine/chemokine release upon stimulation and subsequent immune chemotaxis. Conclusions: Our results indicated HDAC aberration was associated with Foxp3+ Treg deficiency and demonstrated an epigenetic-mediated mechanism underlying immune dysfunction in PAH. Restoration of Foxp3+ Tregs by HDAC inhibitors is a promising approach to resolve pulmonary vascular pathology, highlighting the potential benefit of developing epigenetic therapies for PAH.