American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2020
Comment Randomized Controlled Trial Multicenter StudyRecommended Reading from Boston University School of Medicine Fellows.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Comparative StudyPathological Comparisons of Paraseptal and Centrilobular Emphysema in COPD.
Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE. Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. ⋯ The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P < 0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all P > 0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions. Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Characterization of the Inflammatory Response to Severe COVID-19 Illness.
Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness. ⋯ Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1.
Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1. Objectives: To describe characteristics and outcomes of PH-NF1. Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry. ⋯ Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling. Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.
Rationale: Rifapentine has been investigated at various doses, frequencies, and dosing algorithms, but clarity on the optimal dosing approach is lacking. Objectives: To characterize rifapentine population pharmacokinetics, including autoinduction, and determine optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infection. Methods: Rifapentine pharmacokinetic studies were identified though a systematic review of literature. ⋯ Pharmacokinetic simulations showed that current weight-based dosing leads to lower exposures in individuals with low weight, which can be overcome with flat dosing. In HIV-positive patients, 30% higher doses are required to match drug exposure in HIV-negative patients. Conclusions: Weight-based dosing of rifapentine should be removed from clinical guidelines, and higher doses for HIV-positive patients should be considered to provide equivalent efficacy.