Pulmonary surfactant is a unique mixture of lipids and surfactant-specific proteins that covers the entire alveolar surface of the lungs. Surfactant is not restricted to the alveolar compartment; it also reaches terminal conducting airways and is present in upper airway secretions. While the role of surfactant in the alveolar compartment has been intensively elucidated both in health and disease states, the possible role of surfactant in the airways requires further research. This review summarizes the current knowledge on surfactant functions regarding the airway compartment and highlights the impact of various surfactant components on allergic inflammation in asthma.

The cellular and molecular mechanisms that are involved in airway hyper-responsiveness are unclear. Current studies suggest that tumor necrosis factor (TNF)-α, a cytokine that is produced in considerable quantities in asthmatic airways, may potentially be involved in the development of bronchial hyper-responsiveness by directly altering the contractile properties of the airway smooth muscle (ASM). The underlying mechanisms are not known, but growing evidence now suggests that most of the biologic effects of TNF-α on ASM are mediated by the p55 receptor or tumor necrosis factor receptor (TNFR)1. In addition, activation of TNFR1 coupled to the tumor necrosis factor receptor-associated factor (TRAF)2-nuclear factor-κB (NF-κB) pathway alters calcium homeostasis in ASM, which appears to be a new potential mechanism underlying ASM hyper-responsiveness.

Objective: Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation. Materials and methods: Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects. Results: IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T3, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic Fkbp5, a glucocorticoid-sensitive gene. Conclusion: Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones. This dataset is associated with the following publication: Alewel, D., A. Henriquez, M. Schladweiler, R. Grindstaff, A. Astriab Fisher, S. Snow , T. Jackson, and U. Kodavanti. Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 35(3-4): 59-75, (2023).

Asthma and associated phenotypes are complex traits most probably caused by an interaction of multiple disease susceptibility genes and environmental factors. Major achievements have occurred in identifying chromosomal regions and polymorphisms in candidate genes linked to or associated with asthma, atopic dermatitis, IgE levels and response to asthma therapy. The aims of this review are to explain the methodology of genetic studies of multifactorial diseases, to summarize chromosomal regions and polymorphisms in candidate genes linked to or associated with asthma and associated traits, to list genetic alterations that may alter response to asthma therapy, and to outline genetic factors that may render individuals more susceptible to asthma and atopy due to environmental changes.

This dataset contains ambient air pollution data during the study period and lung function and biomarkers data. This dataset is associated with the following publication: Tong, H., S. Zhang, W. Shen, H. Chen, C. Salazar, A. Schneider, A. Rappold, D. Diaz-Sanchez, R. Devlin, and J. Samet. Lung Function and Short-Term Ambient Air Pollution Exposure: Differential Impacts of Omega-3 and Omega-6 Fatty Acids. Annals of the American Thoracic Society. American Thoracic Society, New York, NY, USA, 19(4): 583-593, (2022).

Frontiers in Toxicology paper, Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats, 2023 Alewel DI. This dataset is associated with the following publication: Alewel, D., T. Jackson, K. Rentschler, M. Schladweiler, A. Astriab Fisher, S. Gavett, P. Evansky, and U. Kodavanti. Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats. Frontiers in Toxicology. Frontiers, Lausanne, SWITZERLAND, 27(5): 1280230, (2023).

The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occuring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

Several recent meta-analyses have shown that the use of SDD can reduce the occurrence of nosocomial pneumonia among ventilated patients in the intensive care unit (ICU) setting. However, the use of SDD has also been demonstrated to increase subsequent patient colonization and infection with antibiotic-resistant bacteria, particularly Gram-positive cocci. Therefore, the routine use of SDD cannot be advocated at the present time. The mortality benefit of SDD appears to occur in surgical/trauma patients, and to be associated primarily with the administration of parenteral antibiotics. This is already an accepted practice in most patients during the perioperative period (eg prophylactic parenteral antibiotics for 24 h). Prolonged decontamination of the aerodigestive tract with topical antimicrobials does not appear to influence outcome, and should not be routinely employed.