Sublingual grass allergen specific immunotherapy: a retrospective study of clinical outcome and discontinuation.

BACKGROUND: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. METHODS: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. RESULTS: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. CONCLUSION: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Upper airway and skin symptoms in allergic and non-allergic asthma: Results from the Swedish GA2LEN study.

BACKGROUND: Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups. METHODS: This cohort (age 17-76 years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire. RESULTS: Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01). CONCLUSION: Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.

Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough.

BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema. OBJECTIVE: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events. METHODS: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons. RESULTS: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10-5, and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10-5. Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10-4) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10-10 and P = 2.6 × 10-4). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups. CONCLUSION: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

Change in health status in COPD: a seven-year follow-up cohort study.

Health status is a prognostic factor included in the assessment of chronic obstructive pulmonary disease (COPD). The aim of our study was to examine the associations of clinical factors with change in health status over a 7-year follow-up period. In 2005, 970 randomly selected primary and secondary care patients with a COPD diagnosis completed questionnaires including the Clinical COPD Questionnaire (CCQ); and in 2012, 413 completed the CCQ questionnaire again. Linear regression used difference in mean total CCQ score between 2005 and 2012 as the dependent variable. Independent variables were CCQ score at baseline 2005, sex, age, educational level, body mass index (BMI), smoking status, heart disease, diabetes, depression, number of exacerbations in the previous 6 months, dyspnoea (modified Medical Research Council (mMRC)). Health status worsened from mean total CCQ (s.d.) 2.03 (1.26) in 2005 to 2.16 (1.37) in 2012 (P=0.011). In linear regression with adjustment for baseline CCQ; older age, lower education, higher mMRC and BMI below 25 kg/m2 at baseline were associated with worsened health status in 2012. When sex, age and all statistically significant measures were included simultaneously in the analysis of the main study group, higher mMRC and BMI below 25 kg/m2 were were associated with deteriorated health status (P<0.0001). A higher level of dyspnoea and lower weight were associated with worse health status in COPD. Strategies for decreasing dyspnoea and awareness of the possible increased risk of worsening disease in under- and normal-weight COPD patients are clinically important.

Comparison of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) in a Clinical Population.

INTRODUCTION: The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) are both clinically useful health status instruments. The main objective was to compare CAT and CCQ measurement instruments. METHODS: CAT and CCQ forms were completed by 432 randomly selected primary and secondary care patients with a COPD diagnosis. Correlation and linear regression analyses of CAT and CCQ were performed. Standardised scores were created for the CAT and CCQ scores, and separate multiple linear regression analyses for CAT and CCQ examined associations with sex, age (≤ 60, 61-70 and >70 years), exacerbations (≥ 1 vs 0 in the previous year), body mass index (BMI), heart disease, anxiety/depression and lung function (subgroup with n = 246). RESULTS: CAT and CCQ correlated well (r = 0.88, p < 0.0001), as did CAT ≥ 10 and CCQ ≥ 1 (r = 0.78, p < 0.0001). CCQ 1.0 corresponded to CAT 9.93 and CAT 10 to CCQ 1.29. Both instruments were associated with BMI < 20 (standardised adjusted regression coefficient (95%CI) for CAT 0.56 (0.18 to 0.93) and CCQ 0.56 (0.20 to 0.92)), exacerbations (CAT 0.77 (0.58 to 0.95) and CCQ 0.94 (0.76 to 1.12)), heart disease (CAT 0.38 (0.17 to 0.59) and CCQ 0.23 (0.03 to 0.43)), anxiety/depression (CAT 0.35 (0.15 to 0.56) and CCQ 0.41 (0.21 to 0.60)) and COPD stage (CAT 0.19 (0.05 to 0.34) and CCQ 0.22 (0.07 to 0.36)). CONCLUSIONS: CAT and CCQ correlate well with each other. Heart disease, anxiety/depression, underweight, exacerbations, and low lung function are associated with worse health status assessed by both instruments.

Determinants of uncontrolled asthma in a Swedish asthma population: cross-sectional observational study.

BACKGROUND: Asthma control is achieved in a low proportion of patients. The primary aim was to evaluate risk factors for uncontrolled asthma. The secondary aim was to assess quality of life associated with asthma control. METHODS: In a cross-sectional study, asthma patients aged 18-75 were randomly selected from primary and secondary health care centers. Postal questionnaires were sent to 1,675 patients and the response rate was 71%. A total of 846 patients from primary and 341 patients from secondary care were evaluated. Data were collected using a questionnaire and review of medical records. The questionnaire included questions about asthma control and a quality-of-life questionnaire, the mini-AQLQ, with four domains (symptoms, activity limitation, emotional function, and environmental stimuli). The mean score for each domain and the overall score were calculated. Asthma control was divided into three levels according to the GINA guidelines and partly and uncontrolled asthma were combined into one group - poorly controlled asthma. RESULTS: Asthma control was achieved in 36% of the sample: 38% in primary and 29% in secondary care. In primary and secondary care, 35 and 45% had uncontrolled asthma, respectively. Risk factors for poorly controlled asthma were female sex [OR 1.31 (1.003-1.70)], older age [OR 2.18 (1.28-3.73)], lower educational level [OR 1.63 (1.14-2.33)], and current smoking [OR 1.68 (1.16-2.43)]. Older age and lower educational level remained statistically significantly associated with poorly controlled asthma when the analyses were limited to never-smokers. Depression was an independent risk factor for poorly controlled asthma in men [OR 3.44 (1.12-10.54)]. The mini-AQLQ scores and the mean overall score were significantly lower in uncontrolled asthma. CONCLUSION: Risk factors for poorly controlled asthma were female sex, older age, low educational level, and smoking. Uncontrolled asthma was significantly associated with lower quality of life.

PI3-kinase regulates eosinophil and neutrophil degranulation in patients with allergic rhinitis and allergic asthma irrespective of allergen challenge model.

The PI3K pathway plays a major role in many vital cell processes. Our primary aim was to investigate signalling through PI3K for in vitro degranulation from allergen-primed eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen challenge. Nine patients with allergic rhinitis, eight with allergic asthma and four controls were studied during birch pollen season and after nasal and bronchial allergen challenge. Primed blood eosinophils and neutrophils were stimulated for in vitro degranulation with C3b-coated Sephadex particles, after prior incubation with Wortmannin, a PI3K inhibitor. The released amounts of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were measured by radioimmunoassay. Wortmannin (10(-6) to 10(-9) M) inhibited ECP, EPO and MPO release in a dose-dependent manner in allergic rhinitis and allergic asthma in all three allergen challenge models. Inhibition of ECP release tended to be lower in the asthmatics in all allergen challenge models, statistically significant compared to the controls during season for 10(-8) M Wortmannin (p=0.01). A clear propensity towards less inhibition in the rhinitic patients was seen after nasal and bronchial challenge compared to seasonal exposure, significant for ECP (10(-8) M Wortmannin; p=0.034 and 0.002, respectively). Signalling through PI3K is clearly involved in ECP, EPO and MPO release in allergic rhinitis and allergic asthma irrespective of allergen challenge model. Allergic asthma demonstrated less inhibition of ECP release via PI3K during pollen season, indicating that other pathways play a greater role in eosinophil degranulation in allergic asthma than allergic rhinitis.

Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge.

BACKGROUND: Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation. METHODS: Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay. RESULTS: C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2%, (p = 0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups. CONCLUSIONS: Systemically activated eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.

Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response.

BACKGROUND AND AIMS: Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high-dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. METHODS: Fifteen birch pollen-allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. RESULTS: Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood-eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 x 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 x 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). CONCLUSIONS: Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis.

Systemic and local eosinophil inflammation during the birch pollen season in allergic patients with predominant rhinitis or asthma.

BACKGROUND: The aim of the study was to investigate inflammation during the birch pollen season in patients with rhinitis or asthma. METHODS: Subjects with birch pollen asthma (n = 7) or rhinitis (n = 9) and controls (n = 5) were studied before and during pollen seasons. Eosinophils (Eos), eosinophil cationic protein (ECP) and human neutrophil lipocalin were analysed. RESULTS: Allergic asthmatics had a larger decline in FEV1 after inhaling hypertonic saline than patients with rhinitis (median) (-7.0 vs.-0.4%, p = 0.02). The asthmatics had a lower sesonal PEFR than the rhinitis group. The seasonal increase in B-Eos was higher among patients with asthma (+0.17 x 109/L) and rhinitis (+0.27 x 109/L) than among controls (+0.01 x 109/L, p = 0.01). Allergic asthmatics and patients with rhinitis had a larger increase in sputum ECP (+2180 and +310 mug/L) than the controls (-146 mug/L, p = 0.02). No significant differences in inflammatory parameters were found between the two groups of allergic patients. CONCLUSION: Patients with allergic asthma and rhinitis have the same degree of eosinophil inflammation. Despite this, only the asthmatic group experienced an impairment in lung function during the pollen season.