Efficacy of bronchial thermoplasty in patients with severe asthma.

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in clinical practice in adults with severe, refractory asthma.Methods: Prospective, single-center, open, observational study comprising patients with uncontrolled asthma (asthma control questionnaire (ACQ) >1.5) and/or frequent exacerbations despite treatment with at least high dose inhaled corticosteroids plus a second controller. Efficacy outcomes was change from baseline 4, 8, 12 and 24 months in FEV1, FVC and FEV1/FVC ratio, asthma control questionnaire (ACQ) score and asthma quality of life score (mini-AQLQ). Results are presented as median with interquartile ranges (IQR). The following were recorded as adverse events: Un-scheduled health care contacts, rescue courses of oral corticosteroid (OCS) and/or antibiotics for exacerbation for exacerbations/respiratory tract infections (RTI).Results: Six-teen patients were enrolled (nine males, median age 50 years; 14 followed for 24 months). Compared to baseline, an improvement in FEV1, FVC, FEV1/FVC ratio, mini-AQLQ and ACQ was observed, i.e.FEV1 (IQR) 1.98 L (1.65-2.45) vs. 2.45 L (2.09-2.93) (p = 0.006), FVC (IQR) 3.23 L (2.76-4.05) vs. 3.75 L (3.22-4.36) (p = 0.041), FEV1/FVC 0.60 (IQR: 0.55-0.70) vs. 0.66 (IQR: 0.63-0.71) (p = 0.016), mini-AQLQ 4.0 (IQR: 3.2-4.9) vs. 5.6 (IQR 4.5-6.5) (p = 0.008, and ACQ 2.9 (IQR: 2.1-3.7) versus 1.5 (IQR 1.0-2.4) (p = 0.004). On the other hand, an increase was observed in unscheduled visits (p = 0.005), as well as use of OCS and antibiotics (p = 0.009 and p = 0.003, respectively).Conclusion: BT in adults with severe asthma improved ACQ, mini-AQLQ and lung function, but resulted in an increased frequency of unscheduled doctor-visits and rescue courses of OCS and antibiotics.

Associations between airway hyperresponsiveness, obesity and lipoproteins in a longitudinal cohort.

BACKGROUND: Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function. The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. METHODS: Associations between AHR, BMI and plasma lipoproteins were assessed in a population-based cohort at ages 14 and 20 years. RESULTS: In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P < 0.05). HDL, LDL/HDL ratio and total cholesterol were not associated with AHR. In multiple regression analyses adjusted for sex, lung function, smoking and asthma, only higher levels of BMI at age 14 or 20 years were significantly associated with increased AHR at age 20 years, while neither LDL, HDL and LDL/HDL ratio nor total cholesterol were significantly associated with AHR. CONCLUSION: We confirmed that in teenagers there is a strong association between BMI and AHR to methacholine. This association seems to be independent of the plasma lipoprotein levels at that age.

Association between prescribing patterns of anti-asthmatic drugs and clinically uncontrolled asthma: a cross-sectional study.

OBJECTIVE: Studies based on prescription data have shown that many asthmatics tend to use large quantities of inhaled beta-2-agonists, suggesting poorly controlled disease. The aim of the present study was to investigate the association between clinically uncontrolled asthma and prescribing patterns of anti-asthmatic drugs with a primary focus on short-acting beta-2-agonists (SABA). METHODS: In a cross-sectional study 357 subjects, selected by their prescriptions of inhaled beta-2-agonists in Odense Pharmaco-Epidemiological Database, underwent individual clinical assessment including the Asthma Control Questionnaire (ACQ) and spirometry. The associations between uncontrolled asthma (ACQ score ≥ 1.50) and individual anti-asthmatic prescribing were analysed by means of logistic regression. RESULTS: Clinically uncontrolled asthma was positively associated with SABA use, the association becoming stronger with higher annual quantity of SABA use, odds ratio (OR) 11.1 (95% CI 4.4-28.0) for ≥400 DDD/year. This trend persisted after stratifying for gender, age, and controller treatment. Although subjects using ≥450 DDD/year were all uncontrolled, there was substantial overlap in SABA use between controlled and uncontrolled subjects below this limit. We found no effect modification by age and gender. Use of inhaled corticosteroids protected against uncontrolled asthma, OR 0.51 (95% CI 0.27-0.95). CONCLUSION: Asthmatics with a high use of SABA frequently have problems with uncontrolled asthma, and users of ICS are protected against uncontrolled asthma. The associations we found were, however, to weak too allow firm conclusions about asthma control for most individual asthma patients.

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. METHODS: Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 µg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-ß2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT. RESULTS: 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. CONCLUSIONS: The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

Impact of socioeconomic status on the use of inhaled corticosteroids in young adult asthmatics.

OBJECTIVE: The aim of this population-based longitudinal study was to examine the associations between socioeconomic status (SES) and anti-asthmatic treatment with inhaled corticosteroids (ICS) among young Danish adult asthmatics, and to investigate whether these associations were consistent over time. METHODS: We extracted data on prescription drug use, education, and income in 97 665 users of anti-asthmatic drugs, aged 18-44 years, identified in Statistics Denmark during 1997-2005. Individual information on education and income was used as measures of SES. Education was categorised into basic school/high school, vocational training, and higher education, and income was categorised into low, middle, and high income. Associations between ICS use and SES were estimated by logistic regression models. RESULTS: High levels of education and income were independently associated with ICS use, education demonstrating the strongest association. Using basic school/high school and low income as baselines, the adjusted odds ratios (ORs) of ICS use for higher education were 1.46 (95% CI 1.40-1.51) and 1.10 (95% CI 1.06-1.14) for high income. Higher education was a nearly constant factor associated with ICS use throughout the observation period, but high income did not demonstrate any association before 2001 with increasing ORs observed each year hereafter. All associations became more pronounced when restricting to 35-44 year-olds. CONCLUSION: High levels of SES were positively associated with ICS use in young adult asthmatics. To encourage ICS use, special attention should be paid to asthmatics with low educational level and low income. Further studies are needed to elucidate underlying mechanisms for this socioeconomic inequality.

No relationship between lung function and high-sensitive C-reactive protein in adolescence.

INTRODUCTION: Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. OBJECTIVE: We explored the temporal relationship between changes in lung function and concentrations of plasma C-reactive protein (CRP) in a population-based cohort study at ages 14 and 20 years using a high-sensitivity CRP assay. METHODS: CRP measurements were performed in a total of 420 subjects at mean age of 13.9 years. Of these, 262 subjects (62%) participated in the follow-up investigation at mean age of 20.1 years. RESULTS: Levels of log-CRP at age 14 were not significantly associated with forced expiratory volume (FEV(1) ) or FEV(1) / forced vital capacity (FVC) ratio at age 20, nor with the change in FEV(1) , FVC or FEV(1) /FVC ratio between 14 and 20 years after controlling for body mass index (BMI), airway hyperresponsiveness (AHR), eosinophil cationic protein (ECP), asthma, smoking, sex, and height at 14 years, and change in height between 14 and 20 years. Sex, BMI, AHR, ECP and change in height between 14 and 20 years were identified as independent factors associated with the change in FEV(1) , FVC and FEV(1) /FVC ratio in adolescence. CONCLUSION: We did not find an association between CRP levels at age 14 and change in lung function by age 20; whereas, sex, change in height, BMI, AHR and ECP were associated with lung function change in adolescence. Our findings indicate that systemic inflammation is of less importance for change in lung function in adolescence. Please cite this paper as: Nybo M, Hansen HS, Siersted HC and Rasmussen F. No relationship between lung function and high-sensitive C-reactive protein in adolescence.

Increased use of inhaled corticosteroids among young Danish adult asthmatics: an observational study.

OBJECTIVE: This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma. METHODS: 106 757 users, aged 18-44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical Product Statistics during 1997-2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models. RESULTS: The one year prevalence of ICS use was constant, approximately 64%, during 1997-2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0.96-1.01) compared to 1.12 (95% CI 1.09-1.15) in 2001, and 1.81 (95% CI 1.75-1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS prescriptions in 2006. CONCLUSION: Treatment with ICS among young Danish adult asthmatics has increased since 2001. This apparent improvement was associated with the introduction of fixed dose combination inhalers with ICS and inhaled long-acting beta-2-agonists. However, there is still room for improvement.

Effect of asthma compliance enhancement training on asthma control in patients on combination therapy with salmeterol/fluticasone propionate: a randomised controlled trial.

OBJECTIVE: We investigated if a higher proportion of adults with previously uncontrolled asthma can achieve total control when given salmeterol/fluticasone propionate (50/250 microg) bid and compliance enhancement training (CET) compared to those given medication alone. METHODS: Open comparison of stable, but uncontrolled, adult asthmatics. After a 12-week treatment period on salmeterol/fluticasone propionate (period 1), patients who failed to achieve control were randomised to continuing treatment with or without CET for 12 weeks (period 2). The primary end point was the proportion achieving total control of their asthma in 7 of the last 8 consecutive weeks of period 2. RESULTS: A total of 361 subjects (50.4% males, mean age 40.0 +/- 14.4 years) in 29 centres were included, of whom 75.9% were randomised into treatment period 2 (n = 140 in the intervention group). The proportion of subjects achieving total asthma control was 8.8% and 7.6%, respectively, in the intervention and control group [not significant (NS)]. Mean morning peak flow, forced expiratory volume in one second (FEV(1)), asthma symptom score and quality of life improved significantly over the study period in both treatment groups. Furthermore, proportion of days with use of rescue medication declined from 59.7% +/- 34.6% (55.7% +/- 35.3%) during screening to 20.3% +/- 29.2% (19.4% +/- 30.9%) during treatment period 2 (NS). CONCLUSION: CET failed to increase the likelihood of achieving total control in asthmatics on salmeterol/fluticasone propionate compared to subjects receiving medication only. However, both groups had a significant improvement in asthma control. (Clinical Trials.gov number, NCT00351143)

Asthma control during the year after bronchial thermoplasty.

BACKGROUND: Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. METHODS: We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed. RESULTS: The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. CONCLUSIONS: Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].).

[The significance of conditions when growing up on the prevalence of atopy in adult Danes]. / Opvaekstforholds betydning for atopiske lidelser hos voksne danskere.

INTRODUCTION: The prevalence of atopy in adults depends on both hereditary and environmental factors. The influence of environmental factors is explained in the "hygiene hypothesis" by maturational changes in the immunological system in response to limited microbiologic challenges in early life. Several studies have indicated protective effects of varying conditions in early life, e.g., living on a farm and in particular with livestock. This study analyses this problem in a Danish population. METHODS: This cross-sectional study used the European Community Respiratory Health Survey (ECRHS) protocol. A screening questionnaire concerning asthma, asthma-related symptoms and nasal allergy supplemented by questions about environmental factors was distributed to 10,000 randomly chosen individuals, 20 to 44 years of age, in five Danish counties. RESULTS: The questionnaire was answered by 7,271 individuals (72.7%). The prevalence of asthma and nasal allergy in adults was independent of growing up in the city or the country, but a significant inverse association was seen when growing up in the country in proximity to livestock. This effect remained after controlling for different hereditary and environmental factors. DISCUSSION: The results of this population-based study are consistent with the results from similar international studies. This study demonstrates that growing up in the country with contact with livestock protects against the development of asthma and nasal allergy in adults.