Fluid filtration rate (FFR) was measured under predominantly zone-three conditions in isolated rabbit lung perfused at constant flow. During forward and reverse perfusion, alveolar hypercapnia ...significantly increased mean pulmonary artery pressure but did not change FFR. We conclude that the pulmonary vasoconstriction induced by alveolar hypercapnia occurs on both arterial and venular sides of the pulmonary circulation.
Human airway epithelium maintains homeostasis of the fluid and salt composition at the airway surface by a regulated transport of sodium and chloride ions. The volume and composition of airway ...surface liquid have been shown to be important in the pathogenesis of cystic fibrosis, nasal inflammatory disease, and nasal polyposis. The presence of functional epithelial sodium and chloride channels in the airway epithelium can be evaluated electrically by measuring the voltage across the nasal epithelium (Vt). Because fluticasone propionate is commonly used to treat nasal inflammatory diseases, we tested its effect on the nasal ion transport.
A single-blind prospective trial was performed on 12 healthy volunteers. Subjects were randomized to receive either fluticasone propionate or normal saline nasal spray twice daily for 2 weeks. We measured the nasal voltage at baseline, days 3 and 14, and 2 weeks after cessation of treatment. The basal voltage, the change in voltage after perfusion with amiloride (sodium channel blocker), and the change in voltage after perfusion with isoproterenol in a low-chloride buffer (chloride channel activator) were recorded. Saccharin clearance times were measured also.
Two-week treatment with fluticasone propionate resulted in a significant increase in the change in Vt after perfusion with amiloride. There was no significant change in the group treated with normal saline. These findings also were observed on day 3 and were reversed completely after the 2-week washout period The increase in amiloride-sensitive Vt did not result in a decrease in mucociliary clearance.
This study suggests that one effect of fluticasone propionate use on nasal mucosa in normal volunteers is increased epithelial sodium absorption.
Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To ...investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC.
We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity.
Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden.
We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.
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