American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Oct 2022
COVID-19-Associated Lung Microvascular Endotheliopathy: A "From the Bench" Perspective.
Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ⋯ Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.
-
Am. J. Respir. Crit. Care Med. · Oct 2022
Evolution of Eczema, Wheeze and Rhinitis from Infancy to Early Adulthood: Four Birth Cohort Studies.
Rationale: The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. Objectives: To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. Methods: We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. ⋯ However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity. Conclusions: Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.
-
Am. J. Respir. Crit. Care Med. · Oct 2022
Traffic-Related Air Pollution and Lung Cancer Incidence: The California Multiethnic Cohort Study.
Rationale: Although the contribution of air pollution to lung cancer risk is well characterized, few studies have been conducted in racially, ethnically, and socioeconomically diverse populations. Objectives: To examine the association between traffic-related air pollution and risk of lung cancer in a racially, ethnically, and socioeconomically diverse cohort. Methods: Among 97,288 California participants of the Multiethnic Cohort Study, we used Cox proportional hazards regression to examine associations between time-varying traffic-related air pollutants (gaseous and particulate matter pollutants and regional benzene) and lung cancer risk (n = 2,796 cases; average follow-up = 17 yr), adjusting for demographics, lifetime smoking, occupation, neighborhood socioeconomic status (nSES), and lifestyle factors. ⋯ Conclusions: These findings in a large multiethnic population reflect an association between lung cancer and the mixture of traffic-related air pollution and not a particular individual pollutant. They are consistent with the adverse effects of air pollution that have been described in less racially, ethnically, and socioeconomically diverse populations. Our results also suggest an increased risk of lung cancer among those residing in low-SES neighborhoods.
-
Am. J. Respir. Crit. Care Med. · Oct 2022
Opioid Use Disorder, Sleep Deficiency, and Ventilatory Control: Bidirectional Mechanisms and Therapeutic Targets.
Opioid use continues to rise globally. So too do the associated adverse consequences. Opioid use disorder (OUD) is a chronic and relapsing brain disease characterized by loss of control over opioid use and impairments in cognitive function, mood, pain perception, and autonomic activity. ⋯ The focus of this concise clinical review is to highlight the bidirectional mechanisms between OUD and sleep deficiency and the potential to target sleep deficiency with therapeutic interventions to promote long-term, healthy recovery among patients in OUD treatment. In addition, current knowledge on the effects of opioids on sleep quality, sleep architecture, sleep-disordered breathing, sleep apnea endotypes, ventilatory control, and implications for therapy and clinical practice are highlighted. Finally, an actionable research agenda is provided to evaluate the basic mechanisms of the relationship between sleep deficiency and OUD and the potential for behavioral, pharmacologic, and positive airway pressure treatments targeting sleep deficiency to improve OUD treatment outcomes.
-
Am. J. Respir. Crit. Care Med. · Oct 2022
Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.
Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. ⋯ Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.