American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · May 2021
Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia.
Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in normal human airway epithelia is missing. Objectives: To identify the cell types that contribute to CFTR expression and function within the proximal-distal axis of the normal human lung. ⋯ Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl- secretion in CF airway secretory cells but not in ciliated cells. Conclusions: Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.
-
Am. J. Respir. Crit. Care Med. · May 2021
Importance of Early COPD In Young Adults for Development of Clinical COPD: Findings from the Copenhagen General Population Study.
Rationale: Individuals who will develop chronic obstructive pulmonary disease (COPD) could be identified at an early age before clinical manifestations appear. Objectives: We investigated risk of clinical COPD 10 years later in young adults from the general population with and without early COPD with a focus on smoking exposure. Methods: We included 14,870 individuals aged 20-100 years from the Copenhagen General Population Study with spirometry 10 years apart. ⋯ Results were validated in the Copenhagen City Heart Study. Conclusions: Depending on amount of smoking exposure, <24% of young adults in the general population with early COPD develop clinical COPD 10 years later. A smoking exposure threshold for early COPD should be reconsidered, as younger individuals are less represented in those with high smoking exposure.
-
Am. J. Respir. Crit. Care Med. · May 2021
Positive End-Expiratory Pressure, Pleural Pressure, and Regional Compliance During Pronation: An Experimental Study.
Rationale: The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Objectives: To compare pleural pressure (Ppl) gradient, ventilation distribution, and regional compliance between dependent and nondependent lungs, and investigate the effect of PEEP during supination and pronation. Methods: We used a two-hit model of lung injury (saline lavage and high-volume ventilation) in 14 mechanically ventilated pigs and studied supine and prone positions. ⋯ Tidal recruitment was more evenly distributed (dependent and nondependent), hyperinflation lower, and lungs cephalocaudally longer in the prone position. Conclusions: In this lung injury model, pronation reduces the vertical pleural pressure gradient and homogenizes regional ventilation and compliance between the dependent and nondependent regions. Homogenization is much less dependent on the PEEP level in prone than in supine positon.
-
Am. J. Respir. Crit. Care Med. · May 2021
Plasma Soluble Suppression of Tumerogenicity-2 Associates with Ventilator Liberation in Acute Hypoxemic Respiratory Failure.
Rationale: Standard physiologic assessments of extubation readiness in patients with acute hypoxemic respiratory failure (AHRF) may not reflect lung injury resolution and could adversely affect clinical decision-making and patient outcomes. Objectives: We hypothesized that elevations in inflammatory plasma biomarkers sST2 (soluble suppression of tumorigenicity-2) and IL-6 indicate ongoing lung injury in AHRF and better inform patient outcomes compared with standard clinical assessments. Methods: We measured daily plasma biomarkers and physiologic variables in 200 patients with AHRF for up to 9 days after intubation. ⋯ Elevated sST2 concentrations on the day of liberation decreased the odds of successful liberation when adjusted for standard physiologic parameters (odds ratio, 0.325; 95% CI, 0.119-0.885; P = 0.03). IL-6 concentrations did not associate with outcomes. Conclusions: Using sST2 concentrations to guide ventilator management may more accurately reflect underlying lung injury and outperform traditional measures of readiness for ventilator liberation.
-
Am. J. Respir. Crit. Care Med. · May 2021
Human Lung Resident Macrophages Co-localize with and Provide Co-stimulation to PD1hi Tissue Resident Memory T Cells.
Rationale: Tissue-resident memory T cells (TRM) play a critical role in the defense against inhaled pathogens. The isolation and study of human lung tissue-resident memory T cells and lung-resident macrophages (MLR) are limited by experimental constraints. Objectives: To characterize the spatial and functional relationship between MLR and human lung tissue-resident memory T cells using ex vivo lung perfusion (EVLP). ⋯ We show that MLR provide costimulatory signaling to PD1hi CD4+ and CD8+ lung TRM,, augmenting the effector cytokine production and degranulation of TRM. Conclusions: EVLP provides an innovative technique to study resident immune populations in humans. Human MLR colocalize with and provide costimulation signaling to TRM, augmenting their effector function.