MP-AzeFlu Improves the Quality-of-Life of Patients with Allergic Rhinitis.

PURPOSE: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities. PATIENTS AND METHODS: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 µg azelastine HCL and 50 µg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from "not at all troubled" (0 mm) to "extremely troubled" (100 mm). RESULTS: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ~14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex. CONCLUSION: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease. REGISTRATION: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019.

Effect of Specific Immunoglobulin E Response and Comorbidities on Effectiveness of MP-AzeFlu in a Real-Life Study.

INTRODUCTION: Phenotyping allergic rhinitis (AR) by immunoglobulin E (IgE) sensitivity and comorbidities may help characterize AR and provide a framework for treatment decisions. METHODS: This prospective, noninterventional study evaluated the effectiveness of MP-AzeFlu (azelastine hydrochloride plus fluticasone propionate intranasal spray formulation) across AR phenotypes. Patients with moderate-to--severe seasonal or perennial AR for whom MP-AzeFlu was prescribed were enrolled. AR subpopulations (ARPs) were assigned based on the classification of IgE response and comorbidities. AR symptoms over the previous 24 h were documented using an AR visual analog scale (AR-VAS), with ratings from "not at all bothersome" (0 mm) to "extremely bothersome" (100 mm), at the inclusion visit and on days 1, 3, 7, and the last day of the study (approximately day 14). AR quality-of-life measures were recorded using a VAS. RESULTS: A total of 1,103 patients with AR were included. Mean baseline AR-VAS scores ranged from 70.3 to 75.1 mm (severe) across ARPs. In the overall population, 86.6% of patients responded to treatment (AR-VAS score <50 mm on ≥1 days). In the ARPs, response rates ranged from 79.3 to 89.6%. Mean reduction in AR-VAS scores ranged from 47.9 to 40.9 mm, a decrease from severe to mild across all ARPs. Quality-of-life VAS scores were similarly reduced in the total population and ARPs. DISCUSSION/CONCLUSION: MP-AzeFlu treatment reduced VAS severity and quality-of-life scores from baseline in the total population and ARPs, supporting MP-AzeFlu as an effective treatment for all patients with moderate-to-severe AR, regardless of AR phenotype or comorbidities.

Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma.

BACKGROUND: Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma. METHODS: This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment. RESULTS: Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241). CONCLUSION: MP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.

Persistence of treatment with 5-grass pollen tablets in patients with allergic rhinitis: a real-life study.

BACKGROUND: In patients with allergic rhinitis, treatment adherence to allergen immunotherapy varies greatly in randomized and real-life studies. OBJECTIVE: To evaluate the use of a 5-grass pollen tablet as sublingual immunotherapy, its treatment persistence, and the reasons for discontinuation in a real-life clinical setting. METHODS: This multicenter, prospective, open-label, noncontrolled observational study evaluated the use of sublingual immunotherapy with a 5-grass pollen tablet in a cross-sectional population of patients (≥5 years old) with grass pollen-induced allergic rhinitis with or without asthma. The primary objective was to determine the percentage of patients persisting with treatment across 1 season in a pre-co-seasonal scheme. Secondary objectives included evaluation of reasons for treatment discontinuation, safety and adverse events; effectiveness (based on physician and patient assessments), and treatment compliance. RESULTS: The study included 196 patients (49.2% male, mean age 27.5 years, range 5.3-65.7 years), with treatment provided by 47 participating physicians. Sixty-seven percent of patients had polysensitivity and 32% had coexistent asthma. On average, patients were treated for 7 months with the 5-grass pollen tablet. After 1 month, 85% of all patients persisted with treatment, and 70% persisted after 7 months. Treatment discontinuation was due chiefly to known side effects (mild to moderate local allergic reactions). Most patients reported symptom improvement; 80% of all patients intended to continue treatment next season. CONCLUSION: Most patients with allergic rhinitis treated pre-co-seasonally with a 5-grass pollen tablet persisted with treatment after the first pollen season. Patients were willing to continue their treatment in the following season owing to improvement of symptoms.

Differences in aerodynamic characteristics of new and dysfunctional Provox 2 voice prostheses in vivo.

Tracheoesophageal voice prostheses need to be replaced due to increased airflow resistance or retrograde leakage of fluid into the trachea as a consequence of biofilm formation. Previous in vitro studies show a change of aerodynamic features of biofilm covered voice prostheses after removal of the prostheses out of the patient. To assess these changes in an in situ situation, aerodynamic characteristics were measured within 45 patients at the beginning and at the end of the wearing process of the Provox 2 voice prosthesis. As a consequence, the influence of biofilm formation on aerodynamic characteristics can be evaluated. In the majority of cases, leakage through the prosthesis was the reason for replacement. No differences were found in the total flow, volume range and intratracheal pressure (ITP) of the voice prostheses measured. The airflow resistance of biofilm covered prostheses was significantly reduced compared to new clean prostheses. However, no correlation was found between the extent of biofilm and the different aerodynamic features measured. Biofilm formation on the Provox 2 is responsible for both reduction in airflow resistance and leakage through the prosthesis by deterioration of the silicone rubber material.

Effect of dairy products on the lifetime of Provox2 voice prostheses in vitro and in vivo.

BACKGROUND: Reduction of biofilm formation on tracheoesophageal voice prostheses by certain dairy products might extend their clinical lifetime. The purpose of this study was to determine the influence of certain dairy products on voice prosthetic biofilms and lifetimes in vitro and in vivo. METHODS: The in vitro results were accomplished using an artificial throat. The lifetimes of Provox2 prostheses were evaluated in a patient group that daily consumed the evaluated products. RESULTS: Buttermilk and Yakult Light fermented milk decreased the amount of bacteria on voice prostheses but stimulated yeast prevalence in vitro. Concurrently, lifetimes of voice prostheses in patients consuming buttermilk were not significantly different, whereas patients consuming Yakult Light fermented milk drink had a significantly (p < .01) increased prosthesis lifetime by a factor of 3.76. CONCLUSION: Yakult Light fermented milk drink reduced biofilm formation on Provox2 prostheses in vitro and in vivo and significantly increased prosthesis lifetime. In vivo, no significant effects were observed for patients consuming buttermilk.

Chronic recurrent multifocal osteomyelitis.

We report what is, to our best knowledge, the first case of chronic recurrent multifocal osteomyelitis (CRMO) in which the frontal and sphenoid bones were involved. Characterized by a prolonged and fluctuating course of osteomyelitis at different sites, CRMO is self-limited, although sequelae can occur. The diagnosis is one of exclusion. It is important to publish cases like this, because the recognition of CRMO can prevent aggressive surgical and medical treatment.

In vitro leakage susceptibility of tracheoesophageal shunt prostheses in the absence and presence of a biofilm.

Although leakage through a tracheoesophageal shunt prosthesis is the main cause of prosthesis failure in a laryngectomy patient, this has never been the subject of in vitro evaluation. The aim of this study was to compare three commercially available voice prostheses by comparison of their in vitro leakage patterns, in absence or presence of a biofilm. To compare in vitro leakage patterns, a model comprised of an artificial throat equipped with a single prosthesis coupled to a water reservoir was developed. By varying the height of the water reservoir, different pressures on the voice prosthesis can be obtained. Both in absence and presence of a biofilm, the Blom Singer voice prosthesis demonstrated the lowest leakage, followed by Groningen Low Resistance. The Provox2 showed significantly the most leakage, however, in presence of a biofilm the leakage of the Provox2 significantly decreased. Regular airflow during biofilm formation significantly increased leakage through the Provox2. Out of 746 clinical replacements, Provox2 showed 76% and Groningen Low Resistance 57% replacements due to leakage. The model used in this study showed significant differences in leakage of the three types of voice prostheses used. Leakage occurred more readily through Provox2 than through Groningen Low Resistance and Blom Singer prostheses, which is in line with clinical observations and enforces the model.

Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat.

OBJECTIVE: To evaluate the preventive effect of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine on biofilm formation on voice prostheses in vitro. MATERIAL AND METHODS: Groningen button and Provox 2 voice prostheses were inoculated with a mixture of bacteria and yeasts isolated from previously explanted Groningen button voice prostheses. After 5 h, separate throats were flushed with buttermilk, Yakult Light fermented milk drink, N-acetylcysteine or phosphate-buffered saline, which served as a control. After 7 days, the microflora on each voice prosthesis was determined. RESULTS: On Groningen button voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine all reduced the amount of both bacteria and yeasts. On Provox 2 voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine reduced the amount of bacteria but, conversely, increased the amount of yeasts. CONCLUSION: These in vitro experiments demonstrate that biofilm formation on voice prostheses is reduced in an artificial throat by the use of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine. However, the structural differences between the type of voice prostheses may influence the ultimate effects.

Effects of maxillary sinus floor elevation surgery on maxillary sinus physiology.

In a prospective study, the effects of elevation surgery of the maxillary sinus floor on maxillary sinus physiology were assessed. Seventeen consecutive patients without preoperative anamnestic, clinical and radiological signs of maxillary sinusitis underwent sinus floor elevation surgery with iliac crest bone grafts. All patients were subjected to unilateral endoscopic examination of the maxillary sinus, taking of a biopsy specimen from the sinus floor mucosa, and collection of a sinus lavage-fluid aspirate. This triad of evaluations was performed immediately preceding the elevation procedure, and 3 months (at implant insertion) and 9 months (at uncovering of implants) postoperatively. All procedures were performed under general anesthesia. Preoperatively, three out of 17 patients showed pre-existing mucosal pathology endoscopically, while the 3- and 9-month results revealed the presence of mucosal pathology in four and two patients, respectively. The 3-month microbiological evaluation showed a significant increase in cultures with bacterial growth, while the 9-month culture results were comparable to the preoperative status of the maxillary sinus. Morphologically, neither fibrosis nor an altered inflammatory response or thickening of the epithelium and lamina propria was observed postoperatively. The number of goblet cells in the epithelial layer was increased. From this study it is concluded that the effect of maxillary sinus floor elevation surgery with autogenous bone grafts does not appear to have clinical consequences in patients without signs of pre-existing maxillary sinusitis.

Maxillary sinus floor elevation surgery. A clinical, radiographic and endoscopic evaluation.

Although augmentation of the maxillary sinus floor with autogenous bone grafts has become a well established preimplantology procedure, its effect on the function of the maxillary sinus has not been the subject of prospective human studies. In this prospective study the effects of sinus floor augmentation on maxillary sinus performance were evaluated. Seventeen consecutive patients who were to undergo augmentation of the maxillary sinus floor with an iliac crest autogenous bone graft agreed to participate in this study. All patients were subject to (i) extensive anamnestic and clinical investigation on sinusitis, (ii) conventional radiography (Waters' projection) and (iii) unilateral endoscopic inspection of the maxillary sinus. This triad of evaluations was performed preoperatively, immediately preceding the augmentation procedure (the maxillary sinus to be inspected endoscopically was randomly selected), and at 3 (at insertion of the implants) and 9 months (at uncovering of implants) postaugmentation. None of the 17 patients showed clinical or radiological signs of actual sinus pathology preoperatively, though 5 patients had a history of an impeded sinus clearance. By contrast, unilateral endoscopic evaluation revealed pre-existing subclinical mucosal pathology in two out of five patients with a history of sinus clearance impairment and in one out of the other 12 patients. At 3 months' postaugmentation, clinical and radiographical examination showed chronic maxillary sinusitis in one non-compromised patient. Moreover, serial unilateral endoscopic evaluation revealed subclinical maxillary mucosal pathology in four other patients (two of whom had a history of an impeded sinus clearance), confirmed by Waters' projection in three of these four patients. At 9 months' postaugmentation, only subclinical maxillary mucosal pathology was detected endoscopically in two patients (one compromised, one non-compromised patient), confirmed by Waters' projection in this last patient. Five implants were lost during the 9-month observation period. As is obvious from this prospective evaluation, the effects of the augmentation procedure on maxillary sinus performance in patients without signs of maxillary sinusitis are of no clinical significance.

Influence of different combinations of bacteria and yeasts in voice prosthesis biofilms on air flow resistance.

Laryngectomized patients use silicone rubber voice prostheses to rehabilitate their voice. However, biofilm formation limits the lifetime of voice prostheses. The presence of particular combinations of bacterial and yeast strains in voice prosthesis biofilms has been suggested to be crucial for causing valve failure. In order to identify combinations of bacterial and yeast strains causative to failure of voice prostheses, the effects of various combinations of bacterial and yeast strains on air flow resistances of Groningen button voice prostheses were determined. Biofilms were grown on Groningen button voice prostheses by inoculating so-called artificial throats with various combinations of clinically relevant bacterial and yeast strains. After 3 days, all throats were perfused three times daily with 250 ml phosphate buffered saline and at the end of each day the artificial throats were filled with growth medium for half an hour. After 7 days, the air flow resistances of the prostheses were measured. These air flow resistances were expressed relative to the air flow resistances of the same prostheses prior to biofilm formation. This study shows that biofilms causing strong increases in air flow resistance (26 to 28 cm water x s/l) comprised combinations of microorganisms, involving Candida tropicalis, Staphylococcus aureus and Rothia dentocariosa.

The influence of antimicrobial peptides and mucolytics on the integrity of biofilms consisting of bacteria and yeasts as affecting voice prosthetic air flow resistances.

The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses afterm biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance.

The influence of radiotherapy on the lifetime of silicone rubber voice prostheses in laryngectomized patients.

OBJECTIVES: To establish a relationship between voice prosthetic lifetime in laryngectomized patients and the irradiation dose applied to the neck node levels (field of the neck) in which the major salivary glands are partially included. Furthermore, a possible relationship between voice prosthetic lifetime and the irradiation dose applied to the primary tumor site was studied. STUDY DESIGN: A retrospective analysis was performed on 101 patients after laryngectomy. METHODS: The records of 101 patients who underwent total laryngectomy between January 1993 and November 1999 at the Department of Otorhinolaryngology, University Hospital Groningen, The Netherlands, were analyzed. The following parameters were obtained: age, sex, radiotherapy, radiation fields, irradiation dose per field, tumor site, TNM classification, and valve insertion. RESULTS: Irradiation to extensive neck fields, including the submandibular glands, did not influence the voice prosthetic lifetime after laryngectomy. However, primary tumor doses exceeding 60 Gray significantly shortened the mean voice prosthetic lifetime per patient. CONCLUSIONS: This study identified an association between radiation on the primary tumor site with a dose equal to or more than 60 Gray and limited lifetimes of voice prostheses.

Comparison of the microbial composition of voice prosthesis biofilms from patients requiring frequent versus infrequent replacement.

This study was performed to establish a possible difference in biofilm composition in patients who require frequent versus infrequent prosthesis replacement. Only Groningen button voice prostheses that were removed because of increased airflow resistance or leakage of food or liquids through the prosthesis were considered for this study. These prostheses were selected from a total of 692 failed voice prostheses over a 2-year evaluation period. The failed voice prostheses were subdivided into a short-lifetime group, corresponding to an implantation period of less than 4 months (20 voice prostheses), and an extended-lifetime group, corresponding to an implantation period of greater than 9 months (18 voice prostheses). The biofilm was removed from the valve sides of the prostheses. The bacterial strain Rothia dentocariosa and the yeast strains Candida albicans I and Candida tropicalis were the predominant strains isolated from the biofilms on the voice prostheses in the short-lifetime group, whereas in the extended-lifetime group, R dentocariosa was found with a fourfold lower isolation frequency and C albicans I was found with a twofold lower isolation frequency. Candida tropicalis was absent from the extended-lifetime group.

The value of Waters' projection for assessing maxillary sinus inflammatory disease.

OBJECTIVE: The significance of the Waters' projection for judging maxillary mucosal disease is, at the least, questionable. The aim of this study was to evaluate the diagnostic use of Waters' projection of the maxillary sinus with particular regard to sinus mucosal swelling as a consistent sign of maxillary sinusitis. STUDY DESIGN: Forty consecutive adult patients were referred to an ear, nose, and throat surgeon for pain in the region of the paranasal sinus, recurrent mucopurulent rhinorrhea, and nasal congestion or obstruction for at least 3 months without any response to conservative treatment. Both conventional radiographs (Waters' projection) and coronal and axial computed tomography (CT) scanning of the maxillary sinuses were recorded. The conventional radiographs and CT scans, all made within an hour, were blinded and assessed in random order by 2 independent well-trained observers with standard radiodiagnostic criteria for sinus mucosal swelling. Intraobserver and interobserver agreements were quantified by calculating Cohen's kappa. The diagnostic significance of the Waters' projection was assessed with the CT scan images as criterion standard by calculating sensitivity and specificity, positive predictive value, likelihood ratio, and diagnostic odds ratio. RESULTS: Cohen's kappa for the intraobserver agreement of Waters' examination was 0.96, and the intraobserver agreement for CT scanning was 0.92. The interobserver agreement for Waters' projection and CT scanning was 0.76 and 0.92, respectively. With CT scanning as criterion standard, the sensitivity and specificity of Waters' projections to detect maxillary sinus mucosal swelling were 83.3% and 69.2%, respectively. The positive predictive (diagnostic) value of Waters' projections was 83.3%, the positive likelihood ratio 2.7, and the diagnostic odds ratio 11.25. CONCLUSIONS: From this study it can be concluded that Waters' projections do not necessarily rule out the presence of maxillary sinus mucosal swelling. Additional examinations may be indicated, especially in patients with compromised sinus clearance.