Why fexofenadine is considered as a truly non-sedating antihistamine with no brain penetration: a systematic review.

OBJECTIVE: Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria. METHODS: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo. RESULTS: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses. CONCLUSION: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.

Pharmacokinetic Evidence of Steady and Sustained Drug Release from Long-Acting Implantable Corticosteroid Matrices for Chronic Rhinosinusitis.

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.

A modest proposal for a new way forward for clinical research: Involve insurance companies.

Is it time for medical insurance companies to organize and fund clinical research that evaluates the role of new treatments (drugs or device-based therapies) in the context of existing clinical paradigms for common diseases?

Complications of nasal SARS-CoV-2 testing: a review.

Transnasal swab testing for the detection of SARS-CoV-2 is well established. The Centers for Disease Control and Prevention advocates swabbing either of the anterior nares, middle turbinate, or nasopharynx for specimen collection depending on available local resources. The purpose of this review is to investigate complications related to transnasal SARS-CoV-2 testing with specific attention to specimen collection site and swab approach. The literature demonstrates that while nasopharyngeal swabbing is associated with an increased risk of complications, it should remain the gold-standard test due to greater diagnostic accuracy relative to anterior nasal and middle turbinate swabs.

Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).

Air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (IAD) such as allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma, and chronic obstructive pulmonary disease (COPD). Oxidative stress in patients with IAD can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. We reviewed emerging data depicting the involvement of oxidative stress in IAD patients. We evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult.

Persistence of Sinonasal Disease Despite Mepolizumab.

The treatment paradigm for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP) is currently undergoing a rapid evolution with the development of monoclonal antibody therapies targeted at type 2 inflammatory pathways. The use of these biologic therapies in asthmatic patients, and more recently, patients with CRSwNP has produced promising results, especially for patients with severe disease. Many questions regarding the appropriate timing of these medications, whether or not these new treatment strategies should be used as a monotherapy or in conjunction with traditional therapies such as sinus surgery, the role of appropriate phenotyping, and identification of biomarkers, remain unanswered. We herein present a case of a patient with severe eosinophilic asthma and comorbid CRSwNP who failed to achieve control of his respiratory symptomology and ultimately progressed to sinus surgery despite treatment with an anti-interleukin 5 monoclonal antibody therapy (mepolizumab). Consideration is given to the mechanistic underpinnings of the reported patient's failure. This case highlights the need for further understanding of the optimal usage of these novel therapeutics in the management of CRSwNP and in the need to better understand the pathophysiology of CRSwNP.

A Pragmatic Approach Towards Sinonasal Diseases.

Sinonasal disease in its multiple forms affects billions of people worldwide. Although physicians train to precisely diagnose a patient and then treat appropriately, the sheer number of people afflicted with sinonasal disease precludes this approach. We argue that patients should first be treated with an intranasal corticosteroid for 2 weeks. Based on their perceived response, they should be triaged. Those who respond well can be instructed on how to continue to manage their disease. Those who do not would be referred to allergists or otolaryngologists for diagnosis and treatment. We believe this pragmatic approach is safe, provided first-line physicians, physician assistants, and nurse practitioners recognize some warning symptoms and signs of serious, but infrequently occurring, sinonasal diseases that would not lend themselves to this proposed approach.

Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health-related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient-reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. METHODS: Following a 4-week mometasone furoate nasal spray run-in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires. RESULTS: Following 16 weeks of treatment, the proportion of patients with moderate-to-severe CRSwNP (VAS > 3-10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT-22, SF-36, and EQ-5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P = .015) and significantly greater improvement (vs placebo) in the SNOT-22 item "reduced productivity." CONCLUSIONS: In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity.

Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with substantial sinus opacification. In a phase 2a study (NCT01920893), dupilumab, a fully human anti-IL-4Rα monoclonal antibody, improved outcomes in CRSwNP refractory to intranasal corticosteroids. We evaluated dupilumab’s effect on sinus opacification in relation to effects on nasal polyp burden, symptoms, and health-related quality of life (HRQoL) in patients with CRSwNP. METHODOLOGY: 16-week randomized, double-blind, placebo-controlled, parallel-group study in 60 adults with CRSwNP. Patients received weekly subcutaneous dupilumab 300-mg or placebo and daily mometasone furoate nasal spray. Sinus opacification was assessed using standard and Zinreich-modified Lundâ€"Mackay (zLMK) scoring. Correlation was assessed between zLMK score and CRSwNP endpoints, including nasal polyp score (NPS), SNOT-22, daily symptom scores, and UPSIT smell-test score. RESULTS: Baseline characteristics were similar across treatment groups. Mean plus/minus SD baseline LMK scores of 18.7 plus/minus 5.5 (placebo) and 18.6 plus/minus 5.0 (dupilumab) indicated severe disease with extensive opacification involving all sinuses. Baseline LMK and LMK scores correlated with NPS severity and loss of sense of smell (daily symptoms; SNOT-22 smell/taste; loss of sense of smell [UPSIT]). At Week 16, dupilumab-treated patients had significantly improved sinus opacification measured by LMK in all individual sinuses vs placebo. Dupilumab also showed similar efficacy with zLMK, with only small differences from LMK, and correlated with SNOT22 smell/taste. The most common adverse events were nasopharyngitis, injection-site reactions, and headache. CONCLUSIONS: In patients with CRSwNP, baseline LMK showed extensive sinus opacification and correlated with symptoms, HRQoL, and hyposmia. Dupilumab treatment reduces opacification across all sinuses and related symptoms in patients with CRSwNP.

Uncharted Waters: Challenges in the Era of Biologic Therapies for Nasal Polyposis.

Several new, promising, targeted therapies for nasal polyposis are being tested in large-scale clinical trials. These agents target pathways thought to be involved in the disease, including IgE, IL-5, IL-4/IL-13, and others. Designing these trials poses significant challenges: who and when to enroll is not completely clear, optimal dosing is not known, outcome measures are insufficiently robust, there are no validated biomarkers, trial regimens may not comport with how clinicians might use these drugs once approved, and cost-benefit ratios have not been assessed. Thus, there is a need to consider such questions, as trials of these novel treatments continue and these biologics become available. Despite these uncertainties about trial design, there remains a great deal of excitement in the field as we approach the dawn of a new era of therapeutic options for nasal polyposis. In this rostrum, we enumerate these issues and call for a conference that will allow stakeholders in the field to confront them as we enter this new era of opportunity to advance the treatment of nasal polyposis.

Monoclonal Antibodies for the Treatment of Nasal Polyps.

Biologics are novel therapeutic medications developed for the targeted therapy for a variety of inflammatory conditions. The biologics currently investigated for the treatment of chronic rhinosinusitis (CRS) with nasal polyps modulate specific inflammatory pathways involved in the pathogenesis of disease. Investigations have focused on the most severe form of the disease, namely, CRS with nasal polyps. It is hoped that specific targeted therapies using these biologics can significantly modulate the immune system, offering both disease control and symptomatic relief. This review summarizes those therapies that have been used to treat nasal polyps.

Allergy and asthma medication use in home-dwelling U.S. older adults.

BACKGROUND: Little is known about the use of allergy and asthma medications in older adults. This study aimed to assess the prevalence of use of these medications in older adults and evaluate predictors of their use. METHODS: Cross-sectional study using data from the National Social Life, Health, and Aging Project (NSHAP), a nationally representative sample of community-dwelling, U.S. adults 57 to 85 years (n = 2976) collected in 2005-2006. We determined prevalence of medication use and used logistic regression to evaluate sociodemographic and health factors associated with their use. RESULTS: Overall prevalence of allergy medication usage was 8.4% (most commonly antihistamines), and prevalence of asthma medication usage was 8.0% (most commonly bronchodilators). Allergy medication use was significantly associated with history of asthma (odds ratio [OR] 2.37; 95% confidence interval [CI], 1.52 to 3.69), chronic obstructive pulmonary disease (COPD) (OR 2.35; 95% CI, 1.58 to 3.51), or nasal surgery (OR 1.97; 95% CI, 1.00 to 3.86). Older age was associated with decreased allergy medication use (per decade, OR 0.80; 95% CI, 0.66 to 0.98). Although increased education was associated with increased overall allergy medication use, it was associated with decreased use of allergy medications generally contraindicated in the elderly. In contrast, the only significant predictors of asthma medication use were history of asthma (OR 19.66; 95% CI, 3.18 to 121.70) or COPD (OR 4.25; 95% CI, 0.88 to 20.44). CONCLUSION: Allergy and asthma medication use is prevalent among older adults and driven mostly by history of asthma or COPD. Additional sociodemographic factors predict allergy (but not asthma) medication use. Further studies are needed to evaluate efficacy of these drugs in the elderly.