Abstract Introduction Recent studies have shown an association of low Vitamin D levels and severity of RLS symptoms. However, effect of treatment of Vit D deficiency on RLS symptoms was not reported, nor were other exacerbating factors for RLS such as iron deficiency or OSA addressed in prior studies, but have been addressed in our study. Methods This is an ongoing study at the JFKMC Sleep Clinic. Eligible Patients with RLS include those with vitamin D 25,hydroxy deficiency (<20 ng/ml), or insufficiency (<30 ng/ml). Such patients will be enrolled in the study after comorbid conditions like iron deficiency and OSA have been adequately corrected. Randomization of the patients will be done by the JFK pharmacy so the patient and provider are blinded to the substance. Substance A or B could be either Vitamin D3 Capsule 50,000 IU, or placebo. Each patient takes A for 6 weeks and then crosses over to B for 6 weeks. Weekly iRLS questionnaires will be collected. Actiwatch Device, to assess activity count per minute, will be worn on the ankle at night for one week time periods: at baseline, at end of 6 weeks of taking A and then at the end of 6 weeks of taking B. Vitamin D levels will also be assessed after each course of supplementation and correlated with subjective and objective findings. Results Between July 7, 2019 to current, 50 consecutive patients seen in sleep clinic with RLS were assessed for vitamin D levels. Ages ranged from 23-86 years. 27 patients were female (54%). Two patients met inclusion criteria and have started their 13-week study. Conclusion This study will help to establish the role of Vitamin D deficiency as a risk factor for RLS, independent of ferritin levels, and comorbid OSA, in affected individuals. This may help to discover a potentially treatable form of RLS. Support No financial support.

Obstructive sleep apnea (OSA) is a major risk factor for incident as well as recurrent stroke, and for increased mortality at 10 year follow up. Most hospitals do not routinely screen for OSA in the acute stroke population, potentially missing this important risk factor. With this quality improvement project, we aim to screen for OSA in the inpatient stroke population, and assess likelihood of referral of stroke patients to an outpatient sleep clinic or sleep study, within 6 weeks of discharge from the hospital. This is an ongoing study to screen all eligible patients who have been admitted to JFK Medical Center stroke unit, with MRI-proven acute ischemic stroke. The nurses take consent and screen patients for OSA using the STOP-BANG questionnaire. A score of >5 is considered at "high" risk. Patients are informed about their score and provided a prescription by the admitting physician, that refers them to an outpatient sleep clinic or a sleep study. The investigators do phone follow up of these patients to assess likelihood of such patients scheduling a sleep clinic/study appointment within 6 weeks after discharge from the hospital. Between Oct 22nd, 2018 to current, 178 patients were admitted to the stroke unit for symptoms suspicious of ischemic stroke. Ages ranged from 25 - 92 years (average 66.5 years). 86 patients (52.7%) were female. 24 patients met inclusion criteria of MRI-proven ischemic stroke. Of those, 3 patients consented to being screened for OSA. Of these, 2 had STOP-BANG scores above 5, and therefore qualified for referral to an outpatient sleep clinic. This ongoing quality improvement project aims to identify rates of referral for sleep evaluation, of stroke patients for who are at high risk for OSA. The ultimate goal of the project is to develop a network-wide protocol for screening of OSA in patients admitted for acute stroke, and establish practical methods for outpatient referral and diagnosis. Support (If Any)

Drop attacks due to cataplexy are usually triggered by laughter, surprise or other emotions. Atonic seizures consist of a spontaneous brief lapse in muscle tone, usually lasting < 15 sec. A 55 year old female had sleepiness, and multiple falls for 4 years but occurring more frequently in the last few months. Mostly, these “drop attacks” were related to hearing a loud sound (e.g. screaming), but not to any emotional situations. Sometimes, she could feel that it is coming. She was on treatment for “vestibular migraines” with Celebrex, Klonopin, Topiramate, Meclizine, prescribed by her neurologist. She was referred to the sleep clinic to rule out narcolepsy with cataplexy. Patient was found to have symptoms of snoring, severely elevated Epworth sleepiness scale sore of 16/24. She did not have sleep paralysis, hypnagogic hallucinations, automatic behaviors or parasomnias. Her systemic and neurological examinations were normal. PSG+MSLT was done after holding Klonopin and Topiramate for 2 weeks. Her PSG showed Moderate OSA with apnea +hypopnea index of 21.3/hour. In the Bipolar array of EEG, it showed recurrent left central sharp waves (at C3) during sleep and less often in wakefulness. Her MSLT showed a mean sleep latency of 5.8 mins suggestive of hypersomnolence, but did not show SOREMP’s. She had also been referred for an ambulatory EEG which showed recurrent left temporal sharp waves during sleep. Therefore, it appears that her drop attacks could be from seizures and her hypersomnolence, due to underlying OSA. Further evaluation is ongoing by epileptologist. Autosomal dominant partial epilepsy with auditory features (ADPEAF) is rare conditions with simple partial seizures, that may be triggered by specific sounds, and likely arise in the lateral temporal lobe. Addition of bi-temporal electrodes in the standard EEG montage for PSG recording will help to better differentiate cataplexy vs seizure.

BACKGROUND: Mobile device-based use of electronic and social media (ESM) is becoming widespread among the young, but its effect on sleep and mood, especially when used after bedtime, remains unclear. OBJECTIVES: To determine the impact of bedtime ESM use on sleep quality, daytime functioning and mood on a sample of American university students. METHODS: An online questionnaire was administered to 105 American university students (age range 18-32 years, mean age 24.4 years [SD 3.7 years], 72% female). Data about sleep habits and ESM use were collected, and validated questionnaires were used to screen for insomnia (Minimal Insomnia Severity Scale), mood disturbances (Personal Health Questionnaire-4) and daytime sleepiness (Epworth Sleepiness Scale). Spearman9s rank correlation coefficient was used to determine significant associations between variables. RESULTS: Nearly all respondents (96%) indicated that they used their mobile devices for ESM use in bed, with 14.2% spending over an hour a night on this activity. Bedtime ESM use was significantly associated with insomnia (r s =0.2, p=0.04) and with mood disturbances (r s =0.2, p=0.04), but not with daytime sleepiness (r s =0.159, p=0.11) or hours of sleep per night (r s =-0.053, p=0.59). CONCLUSIONS: Among a group of young American university students, the use of mobile devices for ESM in bed is extremely common, and has an adverse relationship with insomnia and mood.

Background: Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking.Objective: We sought to compare real-life asthma outcomes and costs of extrafine hydrofluoroalkane (HFA)-beclomethasone and fluticasone administered through a pressurized metered-dose inhaler.Methods: This retrospective matched cohort study examined database markers of asthma control from a large US longitudinal health care claims database over 1 baseline and 1 outcome year for 10,312 patients with asthma aged 12 to 80 years receiving their first ICS as HFA-beclomethasone or fluticasone and matched on baseline demographic characteristics and asthma severity.Results: Patients started on HFA-beclomethasone had significantly higher odds (adjusted odds ratio, 1.19; 95% CI; 1.08-1.31) of achieving overall control (risk and impairment), which was defined as no hospital attendance for asthma, oralcorticosteroids, or antibiotics for lower respiratory tract infection and less than 2 puffs per day of short-acting beta-agonist; they also experienced a lower rate of respiratory-related hospitalizations or referrals (adjusted rate ratio, 0.82; 95% CI, 0.73-0.93) than patients started on fluticasone. Other database outcome measures were similar in the 2 cohorts. Prescribed HFA-beclomethasone doses were lower (P <.001) than fluticasone doses (median, 320 mu g/d [interquartile range, 160320 mg/d] vs 440 mg/d [interquartile range, 176-440 mg/d]). Adjusted respiratory-related health care costs were significantly lower for HFA-beclomethasone than fluticasone (mean, $ 1869 [95% CI, $ 1727-$ 2032] vs $ 2259 [95% CI, $ 2111-$ 2404]), representing a mean annual savings of $ 390 (95% CI, $ 165$ 620) per patient prescribed HFA-beclomethasone rather than fluticasone.Conclusions: Asthma treatment outcomes were similar or better with HFA-beclomethasone prescribed at significantly lower doses and with lower costs than fluticasone.

Introduction: Vorona et al. (2007) described severe OSA responding to chinstrap alone in a patient who had stopped continuous positive airway pressure (CPAP) for two months. They reported improved apnea-hypopnea index (AHI) and oxygen saturation suggesting chinstraps merit investigation as treatment for OSA. We performed this study to evaluate chinstrap as an alternative to CPAP for OSA. Methods: 27 adults with AHIs >5/hr on diagnostic polysomnography (PSG) underwent modified split study (chinstrap alone for first two hours; titration for the rest of the night with CPAP without chinstrap). We compared AHIs and oxygen saturation nadirs during diagnostic PSG with those obtained during the chinstrap portion of the study and the optimal CPAP pressure. Non-parametrical statistical methods were used. Data are presented as median; interquartile range (IQR). Results: There was no statistically significant difference between diagnostic AHI (16.0/hour; 9.8 to 26.0/hour) and chinstrap AHI (22.4/ hour; 10.8 to 40.3/hour). However, there was a statistically significant difference between diagnostic AHI and optimal CPAP AHI (2.3/ hour; 1.0 to 5.2/ hour) (p<0.001). There was no statistically significant difference between the nadirs of the diagnostic oxygen saturation (84.5%; 80.0 to 88.0%) and the chinstrap oxygen saturation (87.0; 84.0 to 89.0%). However, there was a statistically significant difference between diagnostic oxygen saturation nadir and optimal CPAP oxygen saturation nadir (93.0%; 91.0 to 94.3%)(p<0.001). Conclusion: C hinstrap alone does not produce statistically significant improvements in AHI and oxygen saturation nadirs in patients with OSA, and is not an effective alternative to CPAP therapy.

printing supported by . Visit Chiesi at Stand D.30 TUESDAY, SEPTEMBER 27TH 2011 identify, understand and manage the patient issues (A) and whether they reviewed key typical COPD issues (B). The primary endpoint of the study is the comparison of the assessment score (A+B) between the arms. The study has >90% power to detect a 3 point (out of 40) difference between the arms. A pilot study was successfully conducted with 10 PCPs to confirm the feasibility of the study. The study is ongoing and results are expected late 2011. P3765 The Breathing Bus – A primary care model for identifying undiagnosed COPD in hard to reach populations. A pilot study June Roberts1, Helena Cullen2, Nawar Diar Bakerly1. 1Respiratory Medicine, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, United Kingdom; 2Adult Services, Salford Community Health, Salford, Greater Manchester, United Kingdom Background: COPD is frequently undiagnosed especially in socio-economically deprived (SED) populations who are most at risk of this condition. Aims: To improve access to hard to reach groups To identify those most at risk of having undiagnosed COPD and to signpost to general practice for further assessment Methods: A mobile health bus was sited in areas of high SED with good footfall and accessibility. Nurses trained to recognise COPD syptoms, perform FEV6 micro-spirometry and experienced in informal, non-medicalised approaches to health and disease staffed the bus. High risk individuals (over 35 yrs, smoker or ex-smoker with symptoms suggestive of COPD) were targeted for FEV6 microspirometry. Consent was gained to share all results with own GP. Those with unexplained respiratory symptoms and/or abnormal FEV6 readings were asked to see their GP for further assessment. Follow up with patient experience survey took place 8 weeks after a visit to the bus. Results: The bus visited 6 sites on 7 occasions. 350 people visited the bus, between 6% and 87% of contacts were from areas of high SED. Of 119 in the high risk group, 67% men and 45% females had symptoms suggesting COPD and of those suitable for FEV6 readings 30% of men and 38% women had airflow obstruction: all were signposted to their GP. 48% were current smokers. Data from the experience survey indicates that many suspected something was wrong; accessibility and convenience prompted them to come forward for testing. Conclusion: Our pilot work suggests that mobile units in non-clinical settings can increase accessibility to SED groups and prompt high risk individuals to be tested for COPD. Further work is needed. P3766 Two year mortality of COPD in primary care in Greece: An observational study Markos Minas, Ioanna Verou-Katsarou, Parthena Mystridou, Eleni Apostolidou, Hatzoglou Chrisi, Konstantinos Gourgoulianis. Respiratory Medicine Department, University of Thessaly Medical School, Larissa, Greece Introduction: COPD remains a significant cause of death worldwide. However, in primary care in Greece there is still a large proportion of undiagnosed COPD patients. Parameters associated with mortality in COPD patients have not been identified. Aims and objectives: To assess the parameters associated with two year mortality in newly diagnosed COPD patients in primary care in Greece Methods: Using an open spirometry programme, 118 newly diagnosed COPD patients were followed up for two years. Phone contact to assess vital status was performed every six months, whereas the study participants were examined and performed spirometry by the study team once a year after the initial diagnosis. Results: During the two year follow up, a great proportion of COPD patients quitted smoking after the initial diagnosis. However, there was no change in respiratory symptoms, and only the 68.2% showed compliance with treatment. Overall mortality was 28.0% (33 out of 118 subjects). Parameters associated with two year mortality in a cox regression model were age (p<0.001), smoking status (current or former smoker, p=0.025) and history of depression (p=0.001). Conclusion: Mortality of COPD patients in primary care in Greece remains significant high. History of depression was associated with increased mortality and should be taken into account when assessing COPD patients. A more intense monitoring and better health care provided at these patients is suggested. P3767 Exhaled nitric oxide: A useful adjunct test in assessing asthma control in primary care – A cross-sectional exploration Evelien Termeer1, Jiska Snoeck-Stroband2, Hanneke Nuiten1, Persijn Honkoop2, Rik Loymans3, Bart Thoonen4, Ivo Smeele5, Jaap Sont2, Chris van Weel1, Tjard Schermer1. 1Department of Primary and Community Care, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Department of Medical Decision Making, Leiden University Medical Centre, Leiden, Netherlands; 3Department of General Practice, Academic Medical Centre Amsterdam, Amsterdam, Netherlands; 4Diagnostic Centre, SHO, Primary Care Diagnostic Centre Velp, Velp, Netherlands; 5Diagnostic Centre, SHL, Primary Care Diagnostic Centre Breda, Breda, Netherlands Background: Established markers of asthma control, symptoms and lung function do not measure underlying bronchial inflammation and their results are sometimes contradicting. Measuring fractional exhaled nitric oxide (FeNO) as a marker of eosinophilic airway inflammation might offer benefit. Aim: To explore consequences of adding FeNO as an adjunct to symptoms and spirometry for assessing asthma control in primary care. Methods: We performed a cross-sectional analysis of two available cohorts of adult asthmatics. We assessed FeNO, lung function and Asthma Control Questionnaire (ACQ) levels in all participants. Pearson correlation coefficients were calculated between FeNO, ACQ,%FEV1 predicted and%reversibility. In a scenario analysis, patients’ asthma control was categorized according to two established control markers, and with FeNO as an extra marker. Results: We included 147 and 160 patients (in total 63% female; mean age 35.4). Correlations between FeNO, symptoms and lung function were weak (max 0.240, between FeNO and%reversibility). All three control markers were consistent in interpretation of asthma control in 25.7% of the population. In 28.1% symptoms and lung function were consistent but FeNO was contradicting and in another 46.3% the two established markers were contradicting. Conclusions: We observed weak correlations between FeNO, symptoms and lung function in adults with asthma in primary care, which confirms that FeNO is an independent marker in assessing asthma control. In almost half the population, results of symptoms and lung function were contradicting regarding assessing asthma control; in this group FeNO may fine-tune categorization of asthma control. P3768 A pilot study to detect airflow obstruction in smokers using spirometry in a local GP surgery Bhupinder Mann1, Essam Ramhamadany1, Lesley Seddon2, Emma Loveridge3, Angela Glennon3. 1Respiratory Department, West Middlesex University Hospital, London, Middlesex, United Kingdom; 2Maswell Park GP Surgery, Maswell Park, London, Middlesex, United Kingdom; 3Respiratory Section, Astra Zeneca, London, United Kingdom COPD is under diagnosed worldwide. In our locality, it is thought that a fifth of all COPD cases have been identified. Aim: To carry out a pilot study to screen smokers and ex-smokers in a local GP practice with spirometry to allow earlier COPD diagnosis. Methodology: Over a 7 month period, subjects were identified from a GP practice database. The target population included smokers/ex-smokers over the age of 35 who had smoked a minimum of 10 pack years; recurrent or chronic respiratory symptoms; occupational exposure to respiratory irritants or family history of COPD. Patients known to have COPD or asthma were excluded. Appropriate subjects completed a short questionnaire. Severity of airflow obstruction (AFO) was assessed using the UK NICE COPD 2004 guidelines: mild AFO FEV1 50-79% predicted, moderate AFO FEV1 30-49% predicted, severe AFO FEV1 <30% predicted. Spirometry was carried out by a trained nurse. Results: Out of 5,500 patients, 723 subjects were contacted and 203 had spirometry. In total 169 subjects had reliable spirometry which showed normal results in 80 patients (47.3%). AFO was present in 32/169 (18.9%-using NICE criteria). A further 50/169 (corresponding to GOLD stage 1 disease but not in the NICE guidelines) may be at risk giving a figure of 48.4% with AFO and possible COPD.Out of 92 patients who completed the questionnaire, 71 (77.1%) had not heard of COPD and 51% had respiratory symptoms. Conclusion: Proactive screening of smokers with spirometry can increase COPD identification. We are planning to roll this project out using the new NICE COPD 2010 guidelines, which require post bronchodilator spirometry values. This project was funded by Astra Zenica pharmaceutical company. P3769 Effectiveness of supervised training program about spirometry in primary care Cristina Represas-Represas, Virginia Leiro-Fernández, Maribel Botana-Rial, Ana Isabel González-Silva, Alberto Fernández-Villar. Pneumology. Respiratory and Infectious Disease Research Group. Bio-Medical Research Institute of Vigo, University Hospital Complex of Vigo (CHUVI), Vigo, Pontevedra, Spain Spirometry is an essential technique for diagnosing respiratory diseases but it is underused at Primary Care (PC) level. Training could help to improve the situation. Objectives: To analyze the effectiveness of 2 months supervised training program about spirometry performance and interpretation. Methodology: Interventional study, with measurements before and after, to improve the quality. Target population: doctors and nurses team, of 26 PC centers. Teachers: pulmonologists from our hospital (CHUVI). We designed a structured program showed in figure 1. To assess the effectiveness of the course, students were evaluated with a test-exam composed of 5 spirometries with 2 ques

Background: Previous data suggest smoking reduces therapeutic effectiveness in asthma, particularly for corticosteroids (CS) ( Lazarus et al. AJRCCM. 2007;175:783-90 ). This study evaluates montelukast (Mont) 10mg daily and fluticasone propionate (FP) 250μg bid, each compared with placebo (Pbo), in patients with self-reported active smoking (after previous inability to quit) and asthma. Methods: Patients (ages 18-55 years, with asthma [≥1 year], FEV 1 60%-90%predicted, airway reversibility [≥12%], and active smoking [≥0.5 to ≤2 packs/day]) were randomized (after a 3-week, single-blind, placebo run-in) to 1 of 3 parallel, 6-month, double-blind treatment arms. Primary efficacy endpoint was Percent of days with Asthma Control (%days-AC) during treatment; AC was defined as a composite: β-agonist (SABA) ≤2 puffs/day, no nighttime symptoms (N-Sxs), and no unscheduled healthcare (U-Hc) or systemic-CS use. Adverse events (AEs) were also evaluated. Results: The%days-AC over 6 months of treatment was 45% (Mont [N=347]), 49% (FP [N=336]) and 39% (Pbo [N=336]); p-values for Mont and FP (each vs Pbo) were p Conclusion: In a population of asthmatic patients actively smoking cigarettes, both montelukast 10mg daily and fluticasone 250μg bid significantly increased the percent of days with asthma control, compared with placebo.

Background: Using real-life databases to compare asthma treatments requires composite proxies for asthma control. Methods: Observational study using the US Ingenix Normative Healthcare Database to compare asthma outcomes between matched patients either initiating or increasing inhaled corticosteroid (ICS) therapy as fluticasone propionate (FP) or extra-fine hydrofluoroalkane beclomethasone dipropionate (EF HFA-BDP). Literature-based a priori -defined composites were developed and evaluated over 1yr, including: markers of emergency healthcare use for asthma and lower respiratory tract infections; use of oral steroids and reliever therapy; increased maintenance therapy, and controller-reliever ratio. Medication possession ratio (MPR) was calculated to assess adherence. Results: Conclusion: While the proportion of patients achieving asthma control varies according to the considered criterion, data consistently show similar or better outcomes for EF HFA-BDP despite a significantly lower ICS daily dose and similar MPR. Using multiple composite measures to evaluate comparative effectiveness reinforces confidence in study findings.

printing supported by . Visit Chiesi at Stand D.30 TUESDAY, SEPTEMBER 27TH 2011 residual asthmatic inflammation in the peripheral airway. The ECP levels in latephase sputum) 255.2±297.1ug/1 at study entry) significantly decrease 60.0±43.7 (p=0.038) and 50.7±48.4 (p0.049) at 4 and 8 weeks after switching to treatment with the FBC, respectively. The FeNo levels (76.0±69.4 ppb at study entry) also significantly decreased 29.1±15.7 (p=0.017) at 8 weeks. The R5-R20 and AX values of IOS parameters also significantly improved after 8 weeks. Conclusion: This study suggests that the FBC may give better control of residual eosinophilic inflammation in the distal airway compared to SFC therapy. P3952 Montelukast as add-on therapy may improve some indices of small airways involvement in uncontrolled asthmatics Laura Malagrinò1, Francesco Costa1, Lorenza Melosini1, Antonella Di Franco1, Giosuè Catapano2, Pierluigi Paggiaro1. 1Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy; 2Institute of Clinical Physiology,

PURPOSE: To study the effects of long term opioids on breathing patterns in sleep. There have been few studies showing the effect of opioids on respiration during sleep. Teichtahl et. al. (Addiction 2001, 96:, 395-403) reported that stable methadone maintenance patients (MMP) had a higher prevelance of central sleep apnea (CSA). Wang et. al. (CHEST 2005 Sep;128(3):1348-56) showed that 30% of stable MMP patients had CSA, a minority of which could be explained by blood methadone concentration; further research was recommended.

Background: The Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) trial demonstrated that montelukast added to budesonide (MNT + BD) was as efficacious as double the dose of budesonide (dBD) in improving morning peak expiratory flow (AM PEF) in adult asthmatics. Recent studies have demonstrated that montelukast is also effective in treating daytime and nighttime allergic rhinitis (AR) symptoms in asthmatic patients. This analysis was designed to examine whether asthmatic patients with comorbid AR respond differently than patients without comorbid AR in terms of asthma control (lung function).Methods: There were 216 asthmatic patients in the MNT + BD group and 184 patients in the dBD group with AR. Treatment differences in the change from baseline in AM PEF were compared. Least square (LS) mean and 95% confidence interval (CI) were derived from an ANOVA model adjusting for baseline and study site.Results: There was a 9.2% increase in AM PEF from baseline in the MNT + BD group compared with a 6% increase in the dBD group. The LS mean difference [(MNT + BD) - dBD] was 14.2 l/min (P = 0.028). Other secondary endpoints were similar between groups.Conclusion: In the subgroup of asthmatic patients with AR, a combined treatment approach that included montelukast and budesonide provided significantly greater efficacy in reducing airflow obstruction compared with doubling the dose of budesonide. These results support recommendations by the Allergic Rhinitis and its Impact on Asthma initiative that suggest a unified approach aimed at treating the airway inflammation common to both diseases is beneficial for the large proportion of asthmatics who also suffer from AR.

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.

Background. Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Methods. The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n 495), compared with twice-daily, inhaled fluticasone (100 g) (n 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above 7% (a difference of 2 days/month). Results. The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was 2.8% (95% confidence interval: 4.7% to 0.9%), within the noninferiority limit of 7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated. Conclusions. Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with -receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group. Pediatrics 2005;116:360–369; asthma, asthma control, inhaled corticosteroid, safety, randomized controlled trial. ABBREVIATIONS. FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; GINA, Global Initiative for Asthma; ANCOVA, analysis of covariance; CI, confidence interval; RFD, rescue-free day. Asthma is the most prevalent chronic disease of childhood, affecting 4 million children in the United States.1 The number of patients diagnosed with asthma is increasing worldwide,2 particularly among children and adolescents.1,3 Chronic inflammation of the airways is a major component of the pathophysiologic mechanism of asthma. Cysteinyl leukotrienes play a key role in mediating this pathologic process.4 Antileukotriene agents such as montelukast act by blocking the effects of the cysteinyl leukotrienes and have proved very effective in controlling symptoms of asthma among adults and in reducing markers of chronic inflammation among adults5 and children.6,7 Current clinical practice guidelines from the National Heart, Lung, and Blood Institute8 and the Global Initiative for Asthma (GINA)9 recommend the use of antiinflammatory controller therapy for the long-term treatment of persistent asthma. Inhaled corticosteroids (ICS) are recommended and are used widely as first-line controller agents,8,9 with leukotriene-modifying agents being recommended as alternative or add-on therapies. However, clinical trials among adults determined that montelukast is similar to beclomethasone in improving asthma control,10 is similar to triamcinolone in reducing bronchial hyperresponsiveness,11 and acts as an alternative to doubling the dose of inhaled budesonide, on the basis of multiple parameters of asthma control.12 Although the goal of chronic therapy is to maintain control over symptoms and to minimize exacerbations, many clinical trials evaluate the efficacy of a therapeutic regimen based on objective measures of lung function. Studies have reported variable results when comparing montelukast with ICS in improving lung function end points such as peak flow and forced expiratory volume in 1 second (FEV1). To obtain a more complete profile of therapeutic efficacy, measures of asthma control should also address the use of rescue medications and asthma-related health care utilization. Evaluating asthma control with these end points has shown sensitivity and responsiveness in studies among mild asthmatic patients, correlating with patient symptoms.15 Several large clinical trials among adults have From *Pediatric Pneumology and Allergy, Hospital Severo Ochoa Leganes, Madrid, Spain; ‡Department of Pediatric Pneumology and Immunology, Charité, Humboldt University, Berlin, Germany; and §Merck and Co, Whitehouse Station and Rahway, New Jersey. Accepted for publication Dec 2, 2004. doi:10.1542/peds.2004-1172 Conflict of interest: Ms Gilles and Drs Swern, Tozzi, and Polos are employees of Merck and Co. Reprint requests to (P.P.) Merck and Co, WS3D-40, Whitehouse Station, NJ 08889-3400. E-mail: peter polos@merck.com PEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Acad-

Pretreatment of wild-type Chinese hamster ovary (CHO-wt) cells with phytohemagglutinin (PHA) at 37° results in a substantial increase in fusion induced by Newcastle disease virus (NDV) without increasing the amount of virus bound to cells. In contrast, PHA pretreatment at 4° suppresses NDV-induced fusion while increasing the amount of virus bound relative to that bound to untreated control cells at the same temperature. The effects of PHA are reversed within 1–2 hr after incubation of cells at 37° in the absence of lectin. A fusion-resistant cell surface mutant, CHO-15B cells, shows similar results for NDV binding. Both wild-type and mutant cells also bound equivalent amounts of lectin at 4° and 37°. These effects were specific for the leukoagglutinin isolectin of PHA, since the erythroagglutinin isolectin had no comparable effect on either viral attachment or cell fusion. This evidence indicates that the receptors present on CHO cells which control viral attachment, and those which modulate virus-induced fusion, are independently affected by certain lectin pretreatments as well as by mutation.

We report here an assay for quantifying virus-induced lysis, in the absence of antibody and complement, produced within 2 hr after adsorption. This technique makes use of 51CrO4 release from cell monolayers pre-incubated overnight with the isotope. The release of 51Cr is specific for virus-induced lysis and is suppressible by 0.001 M-Ca2+. This assay clearly distinguishes between wild-type Chinese hamster ovary (CHO) cells, clone K and fusion-resistant mutant (CHO-15B), which was found to be resistant to virus-induced cytolysis. The stability of the association of isotope with monolayers of this cell type under the labelling conditions described makes this technique applicable to the study of the cytolytic effects of virus infection.