CFTR expression in human salivary gland acinar cells.

The key role of CFTR in secretory epithelia has been extensively documented. Additionally, CFTR plays a significant role in ion absorption in exocrine glands, including salivary and sweat glands. Most of the knowledge about CFTR expression comes from animal models such as the mouse or the rat, but there is limited information about CFTR expression in human tissues. In the present study, we assessed the expression of CFTR in human submandibular and parotid glands. Consistent with findings in rodent salivary glands, our immunolocalization studies show that CFTR is expressed in duct cells. However, CFTR expression in human salivary glands differs from that in rodents, as immunolocalization and single-cell RNA sequencing analysis from a previous study performed in the human parotid gland revealed the presence of CFTR protein and transcripts within a distinct cell cluster. Based on cell marker expression, this cluster corresponds to acinar cells. To obtain functional evidence supporting CFTR expression, we isolated human parotid acinar cells through collagenase digestion. Acinar cells displayed an anion conductance that was activated in response to cAMP-increasing agents and was effectively blocked by CFTRInh172, a known CFTR blocker. This study provides novel evidence of CFTR expression within acinar cells of human salivary glands. This finding challenges the established model positioning CFTR exclusively in duct cells from exocrine glands.NEW & NOTEWORTHY This study addresses the uncertainty about the impact of CFTR on human salivary gland function. We found CFTR transcripts in a subset of duct cells known as ionocytes, as well as in acinar cells. Isolated human parotid acinar cells exhibited Cl- conductance consistent with CFTR activity. This marks the first documented evidence of functional CFTR expression in human salivary gland acinar cells.

Chronic Rhinosinusitis With Nasal Polyposis Treated With Dupilumab: Real-World Use and Outcomes.

BACKGROUND: Biologic medications are increasingly incorporated into chronic rhinosinusitis with nasal polyps (CRSwNP) management. However, little is known about prescribing patterns in real-world settings and how this relates to proposed international guidelines and outcomes. OBJECTIVES: To characterize use patterns of dupilumab for CRSwNP better in relation to proposed guidelines and explore real-world outcomes. METHODS: We used the TriNetX Web-based tool to identify patients who were prescribed dupilumab for CRSwNP. Patients prescribed dupilumab for a CRSwNP indication were included for analysis. Dupilumab initiation criteria were determined via the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020). RESULTS: In total, 121 patients were identified who were prescribed dupilumab for a CRSwNP indication. Of these, 86 (71%) met EPOS2020 indications for biologic initiation and 35 (29%) did not. Overall, patients had significant improvements in the 22-item SinoNasal Outcome Test scores (mean improvement of 24.3 points) and nasal polyp scores (mean improvement of 1.0 point). However, 20 patients (30%) did not show meaningful improvement in the 22-item SinoNasal Outcome Test scores. Twenty-one patients (17%) failed a previous biologic attempt. Therapy was discontinued by six patients (5%) due to side effects, and by six (5%) owing to a lack of efficacy. CONCLUSIONS: In our experience, patients prescribed dupilumab for CRSwNP frequently may not meet EPOS2020 Guidelines. Over 25% of those who do not meet criteria may not have CRSwNP. Overall, dupilumab use among well-selected patients appears to be safe and effective. Further real-world study of biologic use for CRSwNP will help improve its judicious use and identify populations who benefit most from biologic therapies.

Patterns of Obstruction on DISE in Adults With Obstructive Sleep Apnea Change With BMI.

OBJECTIVES: We describe drug-induced sleep endoscopy (DISE) obstruction patterns in adults with obstructive sleep apnea (OSA) based on body mass index (BMI). We also evaluate subgroups of patients with clinically significant obstruction patterns at the velopharynx and oropharynx. STUDY DESIGN: Retrospective chart review. METHODS: Single-institution, retrospective chart review of adults with OSA who underwent DISE with dexmedetomidine sedation from 2016 to 2018. Endoscopic findings were graded using VOTE (Velum, Oropharynx, Tongue base, Epiglottis) classification. Oropharyngeal obstruction was additionally graded with the modifier T when due to palatine tonsil tissue. Findings in patients who had BMI < 25, 25 ≤ BMI < 30, and BMI ≥ 30 were compared. RESULTS: One hundred and eleven patients (1 underweight, 23 normal weight, 56 overweight, and 31 obese) were reviewed. Patients with lower BMI were more likely to have more severe obstruction at the level of the tongue base (χ2 = 11.52, P = .021) and epiglottis (χ 2 = 10.56, P = .032). Conversely, patients with higher BMI were more likely to have complete concentric (grade 2C) velum obstruction (χ 2 = 16.04, P < .001) and more severe oropharyngeal obstruction (χ 2 = 9.65, P = .046). Patients with grade 2 oropharyngeal obstruction without tonsil obstruction had more severe concurrent velum obstruction compared to subjects with grade 2 T oropharyngeal obstruction (P = .009). CONCLUSION: In adults with OSA, BMI categories have significantly distinct obstruction patterns at all airway levels on DISE, and there appear to be distinct subgroups associated with certain velum and oropharynx collapse patterns. These findings may have important implications for positive airway pressure-alternative treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:224-229, 2021.

Long-Term Maintenance of Acinar Cells in Human Submandibular Glands After Radiation Therapy.

PURPOSE: In a combined retrospective and prospective study, human salivary glands were investigated after radiation treatment for head and neck cancers. The aim was to assess acinar cell loss and morphologic changes after radiation therapy and to determine whether irradiated salivary glands have regenerative potential. METHODS AND MATERIALS: Irradiated human submandibular and parotid salivary glands were collected from 16 patients at a range of time intervals after completion of radiation therapy (RT). Control samples were collected from 14 patients who had not received radiation treatments. Tissue sections were analyzed using immunohistochemistry to stain for molecular markers. RESULTS: Human submandibular and parotid glands isolated less than 1 year after RT showed a near complete loss of acinar cells. However, acinar units expressing functional secretory markers were observed in all samples isolated at later intervals after RT. Significantly lower acinar cell numbers and increased fibrosis were found in glands treated with combined radiation and chemotherapy, in comparison to glands treated with RT alone. Irradiated samples showed increased staining for duct cell keratin markers, as well as many cells coexpressing acinar- and duct cell-specific markers, in comparison to nonirradiated control samples. CONCLUSIONS: After RT, acinar cell clusters are maintained in human submandibular glands for years. The surviving acinar cells retain proliferative potential, although significant regeneration does not occur. Persistent DNA damage, increased fibrosis, and altered cell identity suggest mechanisms that may impair regeneration.