Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Dupilumab effectiveness for the treatment of patients with concomitant atopic dermatitis and chronic rhinosinusitis with nasal polyposis.

Dupilumab is a fully human monoclonal antibody targeting interleukin (IL) 4 and IL13 pathways. We performed a retrospective observational study to evaluate the efficacy of dupilumab for the treatment of adult patients referred to our department, from January 2019 to May 2021, with a diagnosis of moderate to severe atopic dermatitis (AD) and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), with a clinical indication for dupilumab treatment. Skin disease activity was assessed using EASI, Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), and Dermatology Life Quality Index (DLQI). The CRSwNP activity was evaluated using 22-item Sino-Nasal Outcome Test (SNOT-22), endoscopic nasal polyp score (ENPS), nasal congestion or obstruction score (scale 0-3), loss-of-smell score (scale 0-3), and rhinosinusitis disease severity (visual analog scale 0-10 cm). A significant improvement of all the score values was recorded assessing patients at baseline, week (W)16, and W24. In particular, concerning the CRSwNP, a reduction of ENPS score (baseline: 4.9 ± 1.85; W16: 2.49 ± 1.42, p < 0.01; W24: 1.68 ± 1.25, p < 0.01) and SNOT-22 (baseline: 35.9 ± 19.11; W16: 12.85 ± 6.31, p < 0.01; W24: 10.71 ± 7.29, p < 0.01) was observed. Furthermore, dupilumab is a labeled drug for the treatment of both AD and CRSwNP. The use of a single drug to obtain the improvement up to the near remission of AD and CRSwNP increases not only patient's compliance with the treatment, but also the benefits in terms of health cost related to these chronic diseases.

Basophil activation test for Staphylococcus aureus enterotoxins in severe asthmatic patients.

BACKGROUND: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs-the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)-can induce both polyclonal and specific IgE responses. OBJECTIVE: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). METHODS: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1 kU/L and >0.35 kU/L, respectively) were used to assess serum SEsIgE. RESULTS: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35 kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE- SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. CONCLUSIONS: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma.

Clinical impact of nasal budesonide treatment on COPD patients with coexistent rhinitis.

Background: A high percentage of patients with COPD report chronic nasal symptoms. The study aims to evaluate the clinical impact of a 2-month treatment with inhaled nasal budesonide (100 µg per nostril twice daily) in patients affected by COPD with chronic rhinitis comorbidity. Patients and methods: Fifty-three stable COPD patients in therapy according to the Global initiative for chronic Obstructive Lung Disease recommendations were enrolled; 49 completed the study. At enrollment (visit 0), patients underwent skin prick test and rhinoscopy. At visit 0 and after 1 month (visit 1) and 2 months (visit 2) of therapy with nasal budesonide, patients underwent spirometry, and COPD assessment test (CAT), Sinonasal Outcome Test (SNOT 22), and modified Medical Research Council dyspnea scale were administered. Differences in continuous variables, after 2 months of treatment with nasal budesonide, were evaluated using a paired t-test or Wilcoxon matched-pairs signed-ranks test. Results: Two months of treatment with nasal budesonide showed a significant statistical improvement in the total scores of CAT, SNOT 22, and modified Medical Research Council (p<0.001). A significant relationship between CAT and SNOT 22 total scores at baseline and after treatment was observed. Conclusion: The results of the present study indicate the importance of careful evaluation of the presence of chronic nasal symptoms in all COPD patients and suggest beneficial clinical effect from treatment with nasal budesonide in terms of COPD symptoms and quality of life.

In Vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients.

OBJECTIVES: Among the predisposing factors implicated in the immune response to airway bacterial infections, genetic variations of the bitter taste receptor TAS2R38, which is expressed in the cilia of the human sinonasal epithelial cells, seem to be associated with susceptibility to chronic rhinosinusitis (CRS) and in vitro biofilm formation. Polymorphisms in TAS2R38 generate two common haplotypes: the nonfunctional AVI (Alanine, Valine, Isoleucine) and the functional PAV (Proline, Alanine, Valine) alleles, with the latter protecting against gram-negative sinonasal infections. The aim of this study is to investigate for the first time the relevance of TAS2R38 genetic variants in the susceptibility to bacterial infections associated with in vivo biofilm formation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. STUDY DESIGN: A prospective study on 100 adult patients undergoing functional endoscopic sinus surgery (FESS) for CRSwNP. METHODS: Propylthiouracile (PROP) testing and TAS2R38 genotyping were applied to characterize patients for receptor functionality. Sinonasal mucosa samples were processed for microbiological examination and biofilm detection. RESULTS: The nonfunctional genotype is more frequent among CRS patients than in the general population (25% vs. 18.4%, P = 0.034). Airway gram-negative infections are primarily associated with the AVI haplotype (88.9% vs. 11.1% PAV/PAV-functional genotype, P = 0.023). Biofilm formation is prevalent in CRS patients with the AVI nontaster phenotype (62.5% vs. 33.3% PAV taster or supertaster phenotype, P = 0.05). CONCLUSION: Our findings confirm an inverse correlation between TAS2R38 functionality and gram-negative infections in Italian patients with CRSwNP. In addition, for the first time we demonstrated a relationship between in vivo microbial biofilm and TAS2R38 receptor variants. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:E339-E345, 2018.

Cervical necrotizing fasciitis of odontogenic origin involving the temporal region--a case report.

Necrotizing fasciitis (NF) is a soft-tissue infection, usually polymicrobial, that causes necrosis of fascia and subcutaneous tissue while sparing skin and muscle. We report a case of cervical NF complicating dental infection in a 50-year-old woman, who presented with infection involving mucosa of the right mandible and temporal muscle, and masticator spaces, requiring extensive surgery and antibiotic therapy. Prompt diagnosis and immediate aggressive surgical debridement of all compromised tissues are critical to reducing morbidity and mortality in these rapidly progressive infections.

Distracting effect of TV watching on children's reactivity.

The experiment, aimed to evaluate the distracting effect of television, was carried out on 122 children, divided into three groups. All groups performed the auditory vigilance test (AVT) to assess reaction time (RT) to an auditory stimulus and the number of errors in responding to the stimulus. Children in group 1 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a black and white cartoon (BW test). Children in group 2 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a color cartoon (CC test). Group 3 performed SO, BW, and CC tests consecutively. RT and the number and type of errors were measured. In each group, 30 days separated one session from the following. A significant increase of median RTs (more than 10%) and errors (twice and more) was observed both in the case of BW and CC tests with respect to SO test. RT increased throughout all tests. During SO test, errors are mainly "false reactions", but in BW and CC tests, errors are more numerous, and they are mainly "omissions". TV movies have a significant distracting and attention-capturing effect, which increases throughout the vision of the show. No advantage in decreasing this effect is offered by removing color from the movie.

Sensorial saturation for neonatal analgesia.

AIM: Sensorial saturation (SS) is a procedure in which touch, massage, taste, voice, smell, and sight compete with pain, producing almost complete analgesia during heel prick in neonates. SS is an apparently complex maneuvre, but when correctly explained it is easily learnt. In the present paper, we studied its feasibility, assessing whether a long training is really needed to achieve good results. MATERIALS AND METHODS: We enrolled 66 consecutive babies and divided them randomly into 3 groups which received the following forms of analgesia: glucose plus sucking (A), SS performed by nurses (B), SS performed by mothers (C). We did not use perfume on the caregivers' hands, so that babies could smell the natural scent of the hands. We assessed pain level by the ABC scale. RESULTS: Median scores of groups A, B, and C were: 1 (0 to 6), 0 (0 to 4), and 0 (0 to 6), respectively. Mean scores were: 0.6, 0.6, and 1.7 and standard errors were 0.38, 0.22, and 0.32, respectively. Scores of groups B and C were significantly lower than that of A (P=0.03 and 0.006, respectively). No significant difference was found between values of scores of groups B and C. CONCLUSIONS: Even without the use of perfume on the hands, SS was effective as an analgesic maneuvre. It made no difference whether SS was performed by mothers who applied it for the first time or experienced nurses. SS is rapid to learn and any caregiver (mother, pediatrician or nurse) can effectively use it.