The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. We investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes, because we found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. We found that TGF-α, a growth and differentiation factor that is present during wound healing and in psoriasis, increased the expression of both TLR5 and TLR9 on keratinocytes. In addition, TGF-α regulated the function of TLR5 and TLR9, because activation with their respective ligands enhanced the production of IL-8 and human β-defensins. These findings provide evidence that TGF-α up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.

Immaturity of innate immunity contributes to the increased susceptibility of human neonates to infection. The lung is a major portal of entry for potential pathogens in the neonate, and human β-defensins (HBDs) and LL-37 participate in pulmonary innate immunity. We hypothesized that these antimicrobial factors would be developmentally regulated, expressed by neonatal pulmonary tissues, and participate in neonatal innate immunity. We found HBD-2 to be the predominant β-defensin in human neonatal lung. HBD-2 mRNA expression was developmentally regulated, induced by the proinflammatory factor IL-1β, and decreased by dexamethasone. Additionally, HBD-2 abundance in neonatal tracheal aspirates increased as a function of gestational age. HBD-1 had a lower level of expression compared with HBD-2 and was induced by dexamethasone. HBD-3 and LL-37 messages were not detected in airway epithelial cultures. Additionally, each antimicrobial peptide exhibited a unique spectrum of antimicrobial activity and salt sensitivity against bacteria commonly causing sepsis in the neonate. Lower levels of HBD-2 may be one factor contributing to the increased susceptibility of premature infants to pulmonary infections.

Background This study was undertaken to determine if the presence of a clinical pharmacy team impacted patients’ access to cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Methods A retrospective chart review of electronic medical records from the University of Iowa Hospitals and Clinics (UIHC) was conducted. Data were collected regarding the timing of prior authorization (PA) submissions and approvals from 2012 to 2018. The Wilcoxon rank‐sum test was used to compare the meantime (days) between prescription and PA submission dates, and PA submission and approval date for all patients included in the analysis. Comparisons were made for pre‐ and postpharmacy services eras as well as the UIHC Specialty Pharmacy versus a non‐UIHC Specialty Pharmacy. Results Sixty‐three patients were included in the final analysis. The average time between prescription date and PA submission was 12.5 days (standard deviation [SD] = 17.4 days) in the preclinical pharmacy services era and 3.5 days (SD = 5.8 days; P = .028) in the postclinical pharmacy services era. The average time to PA submission significantly decreased from 9.8 days (SD = 13.1 days) to 1.3 days (SD = 4.2 days; P < .0001) when prescriptions were filled by the UIHC Specialty Pharmacy vs a non‐UIHC Specialty Pharmacy. Conclusions There was a significant benefit to CFTR modulator prescribing when clinical pharmacy services were incorporated in our cystic fibrosis (CF) care team, which will become increasingly important with the anticipation of new CF medications in the near future.

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Infection by nontypable Haemophilus influenzae in the airway causes inflammation, and newly isolated strains of these bacteria are associated with an increased risk of disease exacerbation in patients with chronic obstructive pulmonary disease (COPD). In this study we questioned whether strains of H. influenzae associated with exacerbations cause greater inflammation than strains colonizing airways of COPD patients. Bacterial strains were obtained from COPD patients that underwent serial assessment of clinical status, sputum microbiology, and serum antibacterial antibody production. Exacerbation strains were defined as new isolates cultured during exacerbation of clinical symptoms with subsequent development of a homologous bactericidal antibody response. These strains were compared to colonization strains that were not associated with an increase in symptoms or new antibody production. We found that strains of H. influenzae associated with exacerbations caused more airway neutrophil recruitment than colonizer strains in an in vivo mouse model of airway infection. Experiments using an in vitro model of human primary airway epithelial cells revealed that exacerbation strains adhered significantly more to epithelial cells than colonizing strains. Exacerbating strains also induced greater release of interleukin-8 after interaction with airway epithelial cells, a response likely mediated by increased activation of both the nuclear factor-kappaB and p38 mitogen-activated protein kinase signaling pathways. The results indicate that H. influenzae isolated from patients with exacerbations of COPD induce more airway inflammation and likely have differences in virulence compared to colonizing strains. These findings support the concept that H. influenzae infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function.