Efficacy and safety of the Chinese herbal medicine Xiao-qing-long-tang for allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The classic Chinese herbal medicine formula Xiao-qing-long-tang (XQLT) is commonly recommended to manage allergic rhinitis (AR), but the treatment efficacy and safety of XQLT are uncertain. AIM OF THE STUDY: This study aimed to evaluate the effectiveness and safety of XQLT in treating AR. MATERIALS AND METHODS: Nine databases were searched from their inception to April 2021. Randomized controlled trials (RCTs) evaluating XQLT for AR were included. The methodological quality of the studies was assessed using the Cochrane risk-of-bias tool. A meta-analysis and a subgroup meta-analysis were conducted to evaluate the effectiveness of XQLT. RESULTS: Twenty-four RCTs were included in this meta-analysis. XQLT was compared to both placebo and Western medicine (WM), and XQLT combined with WM was compared with WM alone. Meta-analyses were conducted for total nasal symptom scores (TNSS), four individual nasal symptom scores, quality of life (QoL), effective rate, and recurrence rate. The TNSS decreased after XQLT treatment and combination treatment (mean difference (MD): -0.79; 95% confidence interval (CI) [-1.20, -0.38], standardized mean difference (SMD): -1.42; 95% CI [-1.59, -1.24], and SMD: -1.84; 95% CI [-2.08, -1.60]). The two individual nasal symptom scores decreased after XQLT treatment and combination treatment; these nasal symptoms comprised rhinorrhea (SMD: -0.30; 95% CI [-0.58, -0.02] and SMD: -0.48; 95% CI [-0.70, -0.26]), and nasal obstruction (SMD: -0.54; 95% CI [-0.78, -0.30] and SMD: -0.54; 95% CI [-0.76, -0.32). XQLT and XQLT combined with WM achieved a better effective rate than WM (risk ratio (RR): 1.18; 95% CI [1.11, 1.25] and RR: 1.16; 95% CI [1.10, 1.23]) and a lower recurrence rate than WM (RR: 0.24; 95% CI [0.13, 0.43] and RR: 0.47; 95% CI [0.31, 0.72]). XQLT was well tolerated in patients being treated for AR. CONCLUSION: Our results indicated that oral XQLT may alleviate the TNSS, rhinorrhea scores, and nasal obstruction scores of AR and is safe to use in clinical practice. However, more RCTs that follow rigorous methodologies and evaluate well-accepted outcome measures are required to evaluate the effectiveness of XQLT.

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial.

BACKGROUND: Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. METHODS: The phase 3 OSTRO study enrolled patients with severe CRSwNP who were symptomatic despite treatment with intranasal corticosteroids and who had a history of systemic corticosteroid (SCS) use and/or surgery for nasal polyps (NP). Patients were randomized 1:1 to treatment with benralizumab 30 mg or placebo every 4 weeks for the first 3 doses and every 8 weeks thereafter. Coprimary end points were change from baseline to week 40 in NP score (NPS) and patient-reported mean nasal blockage score reported once every 2 weeks. RESULTS: The study population comprised 413 randomized patients (207 in the benralizumab group and 206 in the placebo group). Benralizumab significantly improved NPS and nasal blockage score compared to placebo at week 40 (P ≤ .005). Improvements in Sinonasal Outcome Test 22 score at week 40, time to first NP surgery and/or SCS use for NP, and time to first NP surgery were not statistically significant between treatment groups. Nominal significance was obtained for improvement in difficulty in sense of smell score at week 40 (P = .003). Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects. Benralizumab was safe and well tolerated. CONCLUSION: Benralizumab, when added to standard-of-care therapy, reduced NPS, decreased nasal blockage, and reduced difficulty with sense of smell compared to placebo in patients with CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov NCT03401229.

8-iso-prostaglandin E2 induces nasal obstruction via thromboxane receptor in murine model of allergic rhinitis.

Thromboxane receptor (TP) mediates nasal obstruction, a typical symptom of allergic rhinitis. Since it has been reported that several types of eicosanoids, such as non-enzymatic oxidation product of arachidonic acid isoprostane, act as a TP ligand, there is a possibility that some other eicosanoids contribute to the TP-mediated nasal obstruction. The aim of this study is to investigate the mechanisms of TP-mediated nasal obstruction. Intranasal challenges of ovalbumin (OVA) induced nasal obstruction in mice. Pharmacological blockade of TP receptor but not thromboxane A2 synthase inhibited OVA-induced nasal obstruction. Simultaneous analysis of eicosanoids in nasal lavage fluid and the responses in trans-endothelial resistance suggested that 8-iso-prostaglandin E2 (PGE2 ) can be a candidate for TP ligand. Intranasal challenge of 8-iso-PGE2 induced vascular hyperpermeability and nasal obstruction in TP receptor-dependent manner. Wholemount immunostaining of nasal septum mucosa revealed that 8-iso-PGE2 increased plasma leakage accompanied by distention of venous sinusoids. This study shows that 8-iso-PGE2 is a contributor in TP-mediated nasal obstruction in mice.

Evaluation of Nasal Mucociliary Clearance, Nasal Obstruction Symptom Evaluation, and Epistaxis Severity Score in Isotretinoin Treatment.

OBJECTIVES: The study aims to investigate the possible side effects of isotretinoin use on the nasal mucosa with objective methods in the treatment of acne vulgaris. METHODS: Before the treatment, nasal mucociliary clearance time (MCT) was measured in all patients. Also all patients were asked to complete the questionnaires about the nasal dryness (visual analog scale [VAS]), nasal obstruction (Nasal Obstruction Symptom Evaluation [NOSE]), and presence of epistaxis (Epistaxis Severity Score [ESS]). Both MCT and questionnaires were reevaluated in patients who completed the treatment. RESULTS: The results of 101 patients were evaluated. Before treatment, mean duration of nasal mucociliary clearance (NMC) was 9.55 ± 1.30 minutes, nasal dryness (VAS) value was 2.7 ± 0.7, NOSE score was 2.1 ± 1.1, and ESS score was 1.2 ± 0.7; after treatment, the duration of NMC was 13.80 ± 2.29 minutes, VAS value was 3.3 ± 1.1, NOSE score was 3.2 ± 1.3, and ESS score was 2.1 ± 1.2 (P = .018, .150, .027, .011, respectively). CONCLUSION: The nasal mucosa is adversely affected in patients due to regular use of isotretinoin in the acne treatment, anamnesis should be checked in all nasal surgeries, and routine ear nose throat control should be recommended for these patients.

Effect of Ambient Ozone Exposure Assessed by Individual Monitors on Nasal Function and Exhaled NO Among School Children in the Area of Thessaloniki, Greece.

OBJECTIVES: The study of short-term effects of environmental ozone exposure on nasal airflow, lung function, and airway inflammation. METHODS: Ninety one children-47 underwent rhinomanometry-were included. The study was carried out during the 2013 to 2014 academic year. Activity questionnaires and personal O3 samplers were distributed and 1 week later, respiratory measurements were performed. Daily measurements of outdoor ozone were also considered. RESULTS: A 10 µg/m increase in weekly personal ozone exposure concentrations was associated with a non-statistically significant 12.7% decrease in nasal inspiratory airflow (29.4% during the high ozone period). When the outdoor exposure of the same and the previous day were taken into account the corresponding figures were 13.48% and 43.58% (P = 0.02). CONCLUSIONS: There is an indication for increased risk of nasal obstruction during exposure to high ozone.

Evaluation of the Patient with Nasal Obstruction.

Nasal obstruction is often multifactorial and knowledge of the contributing factors is critical to appropriate evaluation, diagnosis, and execution of a treatment plan. Recognizing and appropriately managing all components of nasal obstruction will increase the likelihood of symptomatic improvement and patient satisfaction.

Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome.

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.

The change in nasal inflammatory markers after intranasal challenges with particulate chitin and lipopolysaccharide: a randomized, double-blind, placebo-controlled, crossover study with a positive control.

BACKGROUND: We investigated the effect of chitin on the inflammation and immune modulation of the nasal mucosa. This compound was compared to placebo and as a positive control we used lipopolysaccharide (LPS). METHODS: Fourteen healthy nonsmoking volunteers 22 to 28 years of age were included. All persons underwent exposure to chitin microparticles (CP) and placebo in a randomized double-blinded fashion. In a last session we used LPS from Enterobacter agglomerans in a single-blinded fashion. There were 2 weeks between each session. The outcome measures were Total Nasal Symptom Score (TNSS) and nasal lavage for cytokines and cells at 0, 3, 4, 8 hours. RESULTS: We showed that CP was only weakly inflammatory compared to LPS. In contrast to the LPS response, we did however show an immune-regulatory effect of CP on enhanced interleukin (IL)-4 and IL-6 responses known to downregulate T helper 2 (Th2) responses, indicating a potential beneficial effect of CP for the regulation of the allergic Th2 immune response. CONCLUSION: This study also shows that CP is well tolerated in healthy volunteers, and that does not induce significantly more symptoms compared to placebo. In fact there is a tendency for CP instillation to induce less rhinorrhoea compared to placebo.

Does usage of a room air freshener affect the nasal mucosa?

BACKGROUND: Effects of chemicals emitted from the room air freshener sprays (RAFSs) on nasal mucosa are still unclear. The purpose of this study was to investigate effects of RAFSs on the nasal mucosa of rats for different time intervals. METHODS: Twenty-eight rats were randomly divided into four experimental groups: group 1 (n = 7) was the control group and not exposed to RAFS or other chemicals, group 2 (n = 7) was exposed to RAFS for 1 month, group 3 (n = 7) was exposed to RAFS for 2 months, and group 4 (n = 7) was exposed to RAFS for 3 months. Samples from the nasal septum were stained using hematoxylin and eosin solution, examined by a pathologist using a light microscope, and analyzed with Fisher's exact test. RESULTS: We observed that distinct histopathological differences in the nasal mucosa of exposed rats depends on different time intervals (p < 0.05). Increased congestion was found after the 1st month of exposure (group 2). Although edema and mild inflammatory cell infiltration, including some eosinophils, was seen after the 2nd month (group 3), squamous metaplasia, numerous eosinophils, and intense inflammatory cell infiltration began after 3 months of exposure (group 4). CONCLUSION: Our results showed that continuous use of RAFS can cause inflammation and eosinophilic infiltration in rats, which begins after 2 months of exposure and may lead to metaplasia after 3 months. Because of differences in body size, geometry, and physiological responses of rats, the extrapolation of these results to humans is not straightforward. However, any such comparison should be made with caution. Finally, more performance is necessary to clarify this subject.

Exposure to PM10 as a risk factor for the development of nasal obstruction and chronic obstructive pulmonary disease.

OBJECTIVES: To investigate whether air pollution is a potential risk factor for airways obstruction. METHODS: A prospective cohort study (11.3 +/- 2.9 years) that took place in two areas (Eordea where concentration of PM10 was high and Grevena, Greece). We used the MRC questionnaire, spirometry, and anterior rhinomanometry at both visits. RESULTS: Initially we examined 3046 subjects. After excluding chronic obstructive pulmonary disease (COPD) patients, we re-examined 872 subjects and 168 of them had developed COPD (Grevena: 24.3%, Eordea: 18.5%). Multivariable logistic regression analysis showed that the area of residence and thus exposure to air pollution was not a risk factor for the development of COPD (OR: 0.51, 95% CI: 0.18-1.46, P = 0.21). On the other hand, residence in Eordea was strongly related to the development of severe nasal obstruction (OR: 11.47, 95% CI: 6.15-21.40, P < 0.001). Similar results were found after excluding patients with COPD stage I as well as in the subgroup of never smokers. CONCLUSION: Air pollution was associated with severe nasal obstruction but not with COPD development.

Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.

UNLABELLED: Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00767416.

Challenge exposure to isocyanates induces changes in nasal patency in patients reporting work-related respiratory symptoms.

OBJECTIVE: To examine the utility of specific inhalation challenge (SIC) in assessing the nasal congestive response to isocyanate exposure. METHODS: Nine patients complaining of work-related respiratory symptoms underwent SIC with exposure to isocyanate for 4 and 120 minutes on different days. Nasal volume was monitored by acoustic rhinometry and nasal congestion by the visual analogue scale (VAS) for up to 6 hours. RESULTS: The 4-minute isocyanate SIC induced a nonsignificant fall in nasal volume and no increase in the VAS score. The 120-minute isocyanate SIC induced a significant fall in nasal volume at 15, 30, and 60 minutes postchallenge that was associated with a significant increase in the VAS score at 15 and 30 minutes postchallenge. CONCLUSIONS: SIC appears useful to assess changes in nasal patency after exposure to isocyanate. Exposure to isocyanates can induce nasal congestion that can be objectively monitored during SIC.

Thirty minute-exposure to aged cigarette smoke increases nasal congestion in nonsmokers.

The aim of this study was to assess the effects of short exposures to experimentally aged cigarette smoke on the nose and upper airways. This crossover study compared the effects of 30-min exposures to (1) experimentally aged cigarette smoke at 1 mg/m³ particulate matter (PM)/14 ppm carbon monoxide (CO) and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco-specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire, objective nasal congestion was assessed by anterior rhinomanometry and nasal nitric oxide (NO) concentrations were determined. Experimentally aged cigarette smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2 nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal resistance in healthy nonsmokers. The rise in nasal resistance was most pronounced in rhinitic subjects. Significant increases were not noted when atopic subjects were considered independent of rhinitis status. Secondhand smoke exposure also elevated subjective nasal symptoms and urinary concentrations of metabolites of nicotine (cotinine and trans-3´-hydroxycotinine) and tobacco-specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in all subgroups of subjects. Exposure-related, subjective nasal symptoms were significantly higher in rhinitic than in normal subjects. Significant changes in nasal NO concentrations were not detected. Data indicate a 30-min exposure to secondhand smoke at 1 mg/m³ PM increases subjective upper respiratory symptoms, increases urinary cotinine and NNAL, and produces objective nasal airflow obstruction in human subjects.

[Clinical review of 33 cases of rhinitis medicamentosa by decongestant nasal spray].

UNLABELLED: Long-term use of decongestant nasal spray (alpha adrenergic agonist) causes nasal congestion by rhinitis medicamentosa. SUBJECTS AND METHODS: We clinically reviewed the cases of 33 patients of rhinitis medicamentosa (23 men, 10 women; mean age, 44.4±15.6 years) treated with nasal steroid sprays instead of decongestant nasal sprays in our clinic from October, 2011 to December, 2012. RESULTS: Periods of drug use were generally long. Only 7 cases had a duration of use less than 1 year, and about half (48.5%) had a duration of use longer than 2 years. Causes of use included acute inflammation (n=6), chronic rhinosinusitis (n=2), and allergic rhinitis (n=20) and unknown cause (n=5). About two-third of the patients failed to answer questions concerning their use of decongestant nasal spray in a questionnaire prior to examination; therefore, careful observation was necessary. Among the 33 cases, 31 were followed up, all of whom showed improvement and stopped using decongestant nasal spays within 4 weeks. Periods for recovery were as follows: 3 days in 19 cases (61.3%) and 1 week in 25 cases (80.6%). Duration of drug use did not correlate with the period required for recovery; therefore, these results suggest that patients with long-term drug use are able to improve quickly. CONCLUSION: Rhinitis medicamentosa with nasal congestion appears readily reversible with suitable treatment.

Excruciating effect of formaldehyde exposure to students in gross anatomy dissection laboratory.

BACKGROUND: Formaldehyde is extensively used for preservation of cadavers in departments of anatomy. However, it is a noxious chemical which may cause serious health problems. OBJECTIVE: To assess the effect of exposure of medical students to formaldehyde at the Department of Anatomy, Niger Delta University, Nigeria. METHODS: In a questionnaire-based study, 93 second-year medical students were surveyed at the Department of Human Anatomy, Niger Delta University, Nigeria. The average duration of exposure for each student in the dissection hall was 6 hr/wk. Participants with history of cough, respiratory or skin diseases were excluded from the study. RESULTS: Out of 93 questionnaires distributed, 75 were completed and returned (response rate: 81%). Of 75 students, 58 (77%) were strongly affected by unpleasant smell of formaldehyde. It was followed by "runny or congested nose" and "redness of the eyes." "Skin-related diseases" was identified as the least ranked effect of formaldehyde. CONCLUSION: Due to the numerous health challenges that formaldehyde causes to students in the gross anatomy dissection laboratories, it cannot be considered as a suitable chemical for embalmment of cadaver for dissection.

Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans.

BACKGROUND: There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 µg/m(3), 400 µg/m(3), and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO), exhaled breath condensate (EBC) and nasal lavage (NAL) samples were collected before, and at various intervals after exposure. RESULTS: No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. CONCLUSION: In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

Intranasal drug-induced fungal rhinopharyngitis.

BACKGROUND: Intranasal drug abuse has long been recognized as an etiology of sinonasal pathology. However, the intranasal use of prescription and nonprescription drugs has surpassed the use of illicit drugs, and the pattern of presentation and required therapeutic intervention appears to be different. We report on our experience with these patients, along with a successful treatment algorithm for this disease process. METHODS: Retrospective chart review of 9 consecutive patients who presented with rhinopharyngitis and a history of intranasal opioid and/or acetaminophen abuse, from 2007 to 2010, at a tertiary referral center. RESULTS: Nine patients were found to have abused intranasal hydrocodone/acetaminophen, oxycodone/aceta-minophen, or acetaminophen and were diagnosed with rhinopharyngitis. Sinonasal pain and odynophagia were the most common chief complaints and 8 of 9 patients reported previous antibiotic failures. On endoscopy, all patients exhibited a thick, white, exudative process involving the nasal septum and lateral nasal mucosa. Five of 9 exhibited large septal perforations. Seven of 9 exhibited white, exudative pharyngitis. Seven of 9 patients had identifiable fungal organisms on culture, including 5 with species of Candida and 3 with Aspergillus. Two patients grew Staphylococcus aureus. Five patients were compliant with follow up. All 5 showed significant improvement in symptoms and examination, following treatment with oral and topical antifungal therapy and nasal irrigations. CONCLUSION: Intranasal opioid and acetaminophen abuse is often associated with the development of fungal rhinopharyngitis. Recognizing that this process is primarily fungal in origin is paramount to successful treatment, as most patients respond well to antifungal therapy when compliant with treatment.

Nasal obstruction as a drug side effect.

Nasal obstruction is a common symptom of various diseases, allergies, and structural deformities and a 'stuffy nose' is one of the most common reasons that patients seek a physician's aid. Drugs that affect the autonomic nervous system are also expected to have a vasoactive effect on the nose. Nasal obstruction in the absence of infectious rhinitis or allergic symptoms may be due to drug use. With the chronic use of a medication, nasal obstruction can change over time and can be underestimated. Very little is known about this topic and very few publications to date solely devoted to drug-induced rhinitis. To prevent complications, obvious nasal obstruction due to drug intake should be treated with appropriate medication(s) or surgical intervention(s).

Paradoxical increase in nasal airway resistance following a topical nasal decongestant spray.

Nasal obstruction is a very common problem associated with common cold and topical nasal decongestant sprays are effective symptomatic treatments causing a decrease in nasal airway resistance (NAR).