Control of allergic rhinitis with MP-AzeFlu: a noninterventional study of a Swedish cohort.

BACKGROUND: The European Union has prioritised allergic rhinitis (AR) control. A visual analogue scale (VAS) has been endorsed as the AR control language and embedded into the most recent MACVIA-ARIA guideline. This study assessed the effectiveness and safety of MP-AzeFlu using a VAS in a real-life study in Sweden. METHODS: 431 patients aged 12 years or over with ARIA-defined moderate to severe AR were included in this multicentre, prospective, non-interventional study and prescribed MP-AzeFlu. Patients assessed symptom severity using a VAS from 0 (not at all bothersome) to 100 mm (very bothersome) on Days 0, 1, 3 and 7, and after approximately 14 days in the morning before using MP-AzeFlu. Patients' perceived level of disease control was assessed on Day 3. The proportion of patients who achieved a defined VAS score cutoff for well- and partly controlled AR was also calculated. RESULTS: MP-AzeFlu reduced mean (SD) VAS score from 67.9 (16.1) mm at baseline to 32.1 (22.8) mm on the last day. Results were consistent irrespective of severity, phenotype, patient age class or previous treatment. By Day 3, 84.0% of patients reported well- or partly controlled symptoms. Overall, 17.7%, 32.2%, 53.8% and 64.2% of patients achieved a 38 mm or greater "well-controlled" VAS score cutoff on Day 1, 3 and 7 and last day, respectively. CONCLUSIONS: MP-AzeFlu provided rapid, effective and sustained symptom control in patients with AR from Sweden in a realworld setting, aligning with EU and MACVIA-ARIA initiatives and supporting the effectiveness of MP-AzeFlu for AR treatment in real life.

Quality of life is improved by endoscopic surgery and fluticasone in nasal polyposis with asthma.

BACKGROUND: The aim was to investigate the health impact of nasal polyposis with asthma and to study effects of endoscopic sinus surgery (ESS), and addition of fluticasone propionate nasal drops (FPND), on health related quality of life (HRQoL). METHODS: Prospective study of 68 patients with nasal polyposis and asthma. Effects were measured with Study 36-Item Short Form (SF-36). A randomized, double-blind, placebo-controlled 14-weeks phase measuring additive effects of FPND 400 µg twice daily (b.i.d.) was included. RESULTS: HRQoL was significantly decreased in both Physical Component Summary, PCS, (45 vs 48, p=0.049) and Mental Component Summary, MCS, (43 vs 51, p<0.001) vs reference population. ESS significantly improved PCS, (p=0.027) and MCS (p=0.021) after five weeks. We found significant additional benefit of FPND on three domains (RP, p=0.002; VT, p=0.007; SF, p=0.002). The increase in HRQoL with FPND reached reference population levels in all domains, as well as in both PCS (50, p=0.003) and MCS (52, p=0.002), five weeks after ESS. CONCLUSIONS: FPND 400 µg b.i.d. can be added to ESS in order to improve, and to reach population levels of, HRQoL already five weeks post-ESS. Physicians should evaluate HRQoL and consider ESS with nasal steroids early in their treatment of these patients.

Evaluation of nasal mucosal swelling and microcirculation throughout nasal and bronchial provocation tests with lysine-aspirin in asthmatics with nasal polyposis.

According to the GA2LEN recommendations, nasal challenge test with lysine-aspirin should be performed only in patients with severe asthma, because the sensitivity of this test has been lower than in bronchial and oral challenge tests. The AIA patient group often have severe asthma with impaired lung function, and therefore improvement of the nasal challenge is warranted. The outcomes of this study clearly indicate that a prolonged detection time from two to three hours might improve the sensitivity of the nasal challenge as a method for diagnosing aspirin intolerance. Moreover, we found a different vascular response in the nasal mucosa in the subjects with AIA after local challenge with lysine-aspirin as compared to an ATA patient group. This puts RSM-LDF as a possible new method in addition to those previously recommended for this particular test.

Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis.

BACKGROUND: Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied. AIM: The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis. METHODS: This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND. RESULTS: Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables. CONCLUSION: Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.

Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis.

As high drug levels at the infection site are desirable for optimal activity, this study explored whether one dose of azithromycin extended release (AZ-ER) achieved higher azithromycin exposure in sinus fluid than azithromycin immediate release (AZ-IR) in adults with acute bacterial sinusitis. Subjects received AZ-ER (2g single dose; n=5) or AZ-IR (500mg daily for 3 days; n=4) and blood and sinus aspirates were collected until 120 h after initial dosing. Within 24 h, exposure was four- and three-fold higher with AZ-ER than with AZ-IR in serum and sinus fluid, respectively. Sinus fluid exposure was five- and three-fold higher than serum for AZ-IR and AZ-ER, respectively. Azithromycin concentrations in sinus fluid were maintained up to 120 h.

Healthcare provider contact for children with symptoms of sleep-disordered breathing: a population survey.

BACKGROUND: Symptoms of sleep-disordered breathing in children, such as frequent snoring, apnoea and choking, may lead to health problems if untreated. The caregiver's level of awareness of these symptoms has been poorly studied. This study aimed to study healthcare provider contact related to sleep-disordered breathing symptoms in a population of children aged 0-11 years. METHODS: A total of 1320 children were randomly selected from a national database that included all children living in Sweden. Caregivers answered a questionnaire about sleep-disordered breathing symptoms during the last month and healthcare provider contact related to these symptoms. RESULTS: A total of 754 answers were received. The prevalence of sleep-disordered breathing symptoms was 4.8 per cent. Of this subgroup, 69 per cent had not been in contact with a healthcare provider regarding their symptoms. CONCLUSION: This study shows that sleep-disordered breathing in children is underestimated and that there is a need to increase caregiver and healthcare provider awareness of sleep-disordered breathing in children.

Airway reactivity and exhaled NO following swine dust exposure in healthy volunteers.

Short-time exposure to swine dust causes an intense inflammation of upper and lower airways and induces increased bronchial responsiveness to methacholine in previously non-exposed healthy volunteers. The objective to this study was to investigate the nasal inflammatory response and mucosal reactivity to swine dust exposure and whether nitric oxide metabolism is involved in the inflammatory process. Nitric oxide in expired air, nasal histamine test (NH), nasal lavage (NAL) and bronchial histamine challenges were studied before and after a 3 h exposure to swine dust in a swine confinement building in 17 non-smoking healthy subjects not previously exposed to farm dust. To detect any interference between NAL and NH, the subjects were divided into two groups: in group 1, NAL was performed after NH and in group 2, NAL preceded NH. Nasal histamine response increased significantly in group 1, but not in group 2 (P=0.012). Albumin levels in NAL were higher before as well as after dust exposure in group 1 compared to group 2 (P=0.036 and 0.015 respectively). Bronchial histamine responsiveness increased following exposure (P= 0.045). Nitric oxide in expired air decreased following bronchial histamine challenge at baseline (P=0.013) but was otherwise unaltered. Short-time exposure to swine dust increases non-specific reactivity of both nose and bronchi. Nasal lavage procedure interferes with nasal histamine test when performed with connection to each other. The inflammatory reaction may involve NO metabolism.

Basal cell carcinoma in the head and neck. The importance of location and histological picture, studied with a new scoring system, in predicting recurrences.

A scoring system for judging the aggressiveness of basal cell carcinomas of the head and neck is devised, based upon 258 tumours from 123 patients. This system is discussed, and we suggest using the depth of growth, the degree of palisading and the narrow epithelial strand formation (narrow strands) as a scoring basis. It is shown that tumours located on the ear are more aggressive than tumours in other places. Tumours on the nose often recur, even though their histological picture is not that aggressive. This phenomenon is also discussed. For proper scoring, an excisional biopsy should be performed unless the tumour is very small. Recurrent tumours and tumours treated with X-ray also have a higher score.

Nasal and bronchial histamine reactivity in patients with allergic rhinitis out of season.

BACKGROUND: The correlation between non-specific hyperreactivity of upper and lower airways in pathologic conditions has not been studied extensively. OBJECTIVE: To investigate the occurrence of nasal and bronchial hyperreactivity in patients with allergic rhinitis studied out-of-season. METHODS: From patients admitted to the Allergy Unit at Stockholm Söder Hospital, 12 individuals with allergic rhinitis due to grass or birch pollen were selected. The nasal mucosa was exposed to increasing concentrations of histamine chloride and the response was recorded by rhinostereometry, an optical method that exclusively measures changes in nasal congestion. Bronchial histamine challenge was performed in connection with the nasal tests, but on different days. RESULTS: The nasal histamine response was significantly greater than in a reference group of healthy volunteers (P < .01). Nasal hyperreactivity was demonstrated in 9 of 12 patients. No clear relation between the magnitude of nasal and bronchial histamine responses was seen in the study group. CONCLUSIONS: In allergic rhinitis studied out-of-season, airway hyperreactivity is common in both upper and lower airways, but does not necessarily occur together in the same individual.

Uncoupled regulation of leukotriene C4 synthase in platelets from aspirin-intolerant asthmatics and healthy volunteers after aspirin treatment.

BACKGROUND: We have reported that thromboxane A2 induces suppression of leukotriene (LT) C4 synthase activity in human platelets. AIM: In the present study, we describe a mechanism whereby aspirin treatment can lead to increased formation of LTC4, which is a potent bronchoconstrictor and inflammatory mediator. This mechanism is also demonstrated to be present in platelets from aspirin-intolerant asthmatics (AIA). METHODS: The effect of arachidonic acid or platelet agonists on LTC4 synthase activity was investigated in platelets obtained from healthy volunteers, aspirin-intolerant asthmatics or aspirin-tolerant asthmatics after in vivo treatment or in vitro pre-incubation with aspirin. RESULTS: Incubation of normal platelets with arachidonic acid or collagen provoked approximately 50% reduction of platelet LTC4 synthase activity, as determined by the conversion of LTA4 to LTC4. However, the inhibitory effect of arachidonic acid or collagen was not observed after oral administration of aspirin prior to collection of the platelets. Arachidonic acid-induced inhibition of LTC4 synthase activity was totally abolished in platelets collected from peripheral blood already 30 min after aspirin ingestion but was fully restored in platelets collected 3 to 7 days after the administration of aspirin. Treatment of platelet suspensions with aspirin in vitro dose-dependently counteracted the suppressive effect of arachidonic acid on LTC4 formation, with total reversal at approximately 40 microm. In contrast, the major aspirin metabolite, salicylic acid did not alter arachidonic acid-induced reduction of LTC4 synthase activity. Similarly, LTC4 synthase activity in platelets from AIA and aspirin-tolerant asthmatics (ATA) was reduced by approximately 50% after pre-treatment with arachidonic acid in vitro. Again the inhibitory effect was abolished when platelets were pre-incubated in the presence of aspirin. CONCLUSION: The results indicate that oral aspirin administration can lead to uncoupling of thromboxane A2-dependent negative feedback mechanisms, which may normally restrict the production of cysteinyl leukotrienes. This mechanism can be of potential interest in aspirin-induced asthma.