Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes.

BACKGROUND: Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined. METHODS/DESIGN: This is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non-atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants. DISCUSSION: The trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627. TRIAL REGISTRATION: Primary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013-003732-72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014.

Predictors of the overlap syndrome and its association with comorbidities in patients with chronic obstructive pulmonary disease.

BACKGROUND: The occurrence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in an individual patient has been described as 'overlap syndrome', which has been associated with poor prognosis. Little is known about the possible predictors of the overlap syndrome and its association with comorbidities contributing to impaired outcome. OBJECTIVES: This study aimed to evaluate the prevalence and possible predictors of the overlap syndrome and its association with comorbidities in a cohort of COPD patients. METHODS: Individuals with COPD (GOLD stages I-IV, risk groups A-D) were recruited from outpatient clinics. Information on age, gender, body mass index (BMI), smoking status, Epworth sleepiness scale (ESS), COPD assessment test, comorbidities, medications and exacerbations in the past year was collected and a spirometry was performed. Participants underwent a nocturnal polygraphy using the ApneaLink™ device at home. An apnea-hypopnea index (AHI) >10 per hour was considered to indicate OSA. RESULTS: We enrolled 177 COPD patients (112 men) with a mean age of 64 years (range 42-90), of whom 35 (20%) had an ESS score above 10. During nocturnal polygraphy, 33 patients (19%) had evidence of OSA. In multivariate analysis, BMI and pack years were positively associated with AHI, independent of other significant AHI determinants from univariate analysis. Arterial hypertension and diabetes were more common in patients with the overlap syndrome. CONCLUSIONS: Almost 20% of COPD patients also have OSA. BMI and smoking history seem to be predictors of the overlap syndrome, and these patients may be more often affected by hypertension and diabetes.

Differences in classification of COPD patients into risk groups A-D: a cross-sectional study.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease proposed in 2011 a new system to classify chronic obstructive pulmonary disease (COPD) patients into risk groups A-D, which considers symptoms and future exacerbation risk to grade disease severity. The aim of this study was to investigate the agreement between COPD risk group classifications using COPD assessment test (CAT) or modified Medical Research Council (mMRC) and severity grades or past-year exacerbations. Furthermore, physical activity across risk groups was examined. METHODS: 87 patients with stable COPD were classified into risk groups A-D. CAT and mMRC were completed. Severity grades I-IV were determined using spirometry and the number of past-year exacerbations was recorded. To test the interrater agreement, Cohen's Kappa was calculated. Daily physical activity was measured by the SenseWear Mini armband. RESULTS: Using CAT, 65.5% of patients were in high-symptom groups (B and D). With mMRC, only 37.9% were in B and D. Using severity grades, 20.7% of patients were in high-exacerbation risk groups (C and D). With past-year exacerbations, 9.2% were in C and D. Interrater agreement between CAT and mMRC (κ = 0.21) and between severity grades and past-year exacerbations (κ = 0.31) was fair. Daily steps were reduced in risk groups B and C + D compared to A (p < 0.01), using either classification. CONCLUSIONS: When classifying COPD patients into risk groups A-D, the use of CAT or mMRC and severity grades or past-year exacerbations does not provide equal results. Daily steps decreased with increasing COPD risk groups.

Daily physical activity, functional capacity and quality of life in patients with COPD.

INTRODUCTION: In the therapy of chronic obstructive pulmonary disease (COPD), it is a major goal to improve health-related quality of life (HRQOL). Patients with COPD often suffer from exertional dyspnea and adopt a sedentary lifestyle, which could be associated with poorer HRQOL. The aim of this study was to investigate the independent association of objectively measured daily physical activity and functional capacity with HRQOL in patients with COPD. METHODS: In this cross-sectional study conducted at the University Hospital Basel, Switzerland, 87 stable patients (58.6% male, mean age: 67.3 ± 9.6 yrs) with COPD in GOLD grades I (n = 23), II (n = 46), III (n = 12) and IV (n = 6) were investigated. To assess HRQOL, the COPD assessment test (CAT) was completed. Patients performed spirometry and 6-min walk test. Physical activity was measured by the SenseWear Mini Armband on 7 consecutive days. By performing a multiple linear regression analysis, independent predictors of CAT score were identified. RESULTS: Age (ß = -0.39, p = 0.001), average daily steps (ß = -0.31, p = 0.033) and 6-min walk distance (ß = -0.32, p = 0.019) were found to be independent predictors of CAT score, whereas physical activity duration above 3 METs (p = 0.498) and forced expiratory volume in 1 s in% of predicted (p = 0.364) showed no significant association. CONCLUSIONS: This study showed that average daily steps and functional capacity are independent determinants of HRQOL in patients with COPD. This emphasizes the importance to remain active and mobile, which is associated with better HRQOL.