Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Oct 2023
Tissue Perfusion and Diffusion and Cellular Respiration: Transport and Utilization of Oxygen.
This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. ⋯ Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.
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Semin Respir Crit Care Med · Aug 2023
Multicenter StudyExpert Review on Nonsurgical Management of Parapneumonic Effusion: Advances, Controversies, and New Directions.
Parapneumonic effusion and empyema are rising in incidence worldwide, particularly in association with comorbidities in an aging population. Also driving this change is the widespread uptake of pneumococcal vaccines, leading to the emergence of nonvaccine-type pneumococci and other bacteria. Early treatment with systemic antibiotics is essential but should be guided by local microbial guidelines and antimicrobial resistance patterns due to significant geographical variation. ⋯ The IET dosing regimen used in the UK Multicenter Sepsis Trial -2 has the most evidence available but data surrounding alternative dosing, concurrent and once-daily instillations, and novel fibrinolytic agents are promising. Prognostic scores used in pneumonia (e.g., CURB-65) tend to underestimate mortality in parapneumonic effusion/empyema. Scores specifically based on pleural infection have been developed but require validation in prospective cohorts.
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Semin Respir Crit Care Med · Aug 2023
ReviewMalignant Pleural Effusions in the Era of Immunotherapy and Antiangiogenic Therapy.
Malignant pleural effusions (MPE) have historically been associated with a poor prognosis, and patients often require a series of invasive procedures and hospitalizations that significantly reduce quality of life at the terminus of life. However, advances in the management of MPE have coincided with the era of immunotherapies, and to a lesser extent, antiangiogenic therapies for the treatment of lung cancer. Landmark studies have shown these drugs to improve overall survival and progression-free survival in patients with lung cancer, but a paucity of phase III trial data exists for the impact of immune checkpoint inhibitors (ICI) on lung cancers associated with MPE. ⋯ The diagnostic and prognostic values of vascular endothelial growth factor and endostatin expression levels in malignancy will also be discussed. These advancements are changing the paradigm of MPE management from palliation to treatment for the first time since 1767 when MPE was first reported. The future holds the promise of durable response and extended survival in patients with MPE.
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Semin Respir Crit Care Med · Aug 2023
ReviewIntrapleural Anticancer Therapy for Malignant Pleural Diseases: Facts or Fiction?
Malignant pleural diseases involves both primary pleural malignancies (e.g., mesothelioma) as well as metastatic disease involving the pleura. The management of primary pleural malignancies remains a challenge, given their limited response to conventional treatments such as surgery, systemic chemotherapy, and immunotherapy. ⋯ We review the role intrapleural chemotherapy, immunotherapy, and immunogene therapy, as well as oncolytic viral, therapy and intrapleural drug device combination. We further discuss that while the pleural space offers a unique opportunity for local therapy as an adjuvant option to systemic therapy and may help decrease some of the systemic side effects, further patient outcome-oriented research is needed to determine the exact role of these treatments within the armamentarium of currently available options.
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Coronavirus disease 2019 (COVID-19)-related pleural diseases are now well recognized. Since the beginning of the pandemic, increasing cases of pleural diseases including pneumothorax, pneumomediastinum, and pleural effusion with severe COVID-19 infection have attracted the attention of physicians and are not incidental or due to barotrauma. The complicated course of COVID-19 illness highlights the complex pathophysiological underpinnings of pleural complications. ⋯ Conversely, pleural effusion cases, although sharing some similar patient characteristics with pneumothorax and pneumomediastinum, are in general managed more conservatively. The evidence suggests that patients with COVID-19-related pleural diseases, either due to air leak or effusion, have more severe disease with a worse prognosis. This implies that prompt recognition of these complications and targeted management are key to improve outcomes.