[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

Anatomic Features of the Nasal and Pharyngeal Region Do Not Influence PAP Therapy Response.

The objective of this study was to investigate to which extent anatomic features of the nasal and pharyngeal region contribute to the severity of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy response. Therefore, 93 patients (mean age 57.5 ± 13.0 years, mean body mass index 32.2 ± 5.80 kg/m2, 75 males, 18 females) diagnosed with OSA who subsequently started PAP therapy were randomly selected from the databank of a sleep laboratory of a tertiary university medical center. Patients were subdivided based on nasal anatomy (septal deviation, turbinate hyperplasia, their combination, or none of the above), pharyngeal anatomy (webbing, tonsillar hyperplasia, their combination, or none of the above), and (as a separate group) tongue base anatomy (no tongue base hyperplasia or tongue base hyperplasia). Then, polysomnographic data (e.g., arousal index, ARI; respiratory disturbance index, RDI; apnea index, AI; hypopnea index, HI; and oxygen desaturation index, ODI) of diagnostic polysomnography (PSG) and PAP therapy control PSG were collected, grouped, and evaluated. Septal deviation, turbinate hyperplasia, or their combination did not significantly affect the assessed PSG parameters or the response to PAP therapy compared with patients without nasal obstruction (p > 0.05 for all parameters). Accordingly, most PSG parameters and the response to PAP therapy were not significantly affected by webbing, tonsil hyperplasia, or their combination compared with patients without pharyngeal obstruction (p > 0.05 for RDI, AI, HI, and ODI, respectively). However, in the pharyngeal anatomy group, ARI was significantly higher in patients with tonsil hyperplasia (p = 0.018). Further, patients with tongue base hyperplasia showed a significantly higher HI in the diagnostic PSG (p = 0.025) compared with patients with normal tongue base anatomy, but tongue base anatomy did not significantly affect the response to PAP therapy (p > 0.05 for all parameters). The influence of anatomic features of the nasal and pharyngeal region on PAP therapy response appears to be small, and generalizability of these results requires further studies.

BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression.

Here, we describe the expression of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients.