Maria Gerhardsson de Verdier

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach. This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements. Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids. Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach. Severe asthma results in more airway inflammation, worse symptoms and lower lung function, despite increased therapy http://ow.ly/QznR3

Prevalence of knee pain and knee OA in southern Sweden and the proportion that seeks medical care

OBJECTIVE The aim of this study was to estimate the prevalence of frequent knee pain in radiographic, symptomatic and clinically defined knee OA in middle-aged and elderly patients and the proportion that seeks medical care. METHODS In 2007 a random sample of 10 000 56- to 84-year-old residents of Malmö, Sweden, were questioned about knee pain. We classified subjects reporting knee pain with a duration of at least 4 weeks as having frequent knee pain. A random sample of 1300 individuals with frequent knee pain and 650 without were invited for assessment by the ACR clinical knee OA criteria and for bilateral weight-bearing knee radiography. We considered a Kellgren-Lawrence grade ≥2 as radiographic knee OA and that in combination with frequent knee pain as symptomatic knee OA. By linkage with the Skåne Healthcare Register, we determined the proportion of subjects that had consulted for knee OA or pain. RESULTS The 10 000 subjects had a mean age of 70 years (s.d. 7.6), a mean BMI of 27.1 kg/m(2) and 62% were women. The prevalence of frequent knee pain was 25.1% (95% CI 24.1, 26.1), higher in women and similar across age groups. The prevalence of radiographic knee OA was 25.4% while 15.4% had either symptomatic or clinically defined knee OA. Of these, 68.9% consulted a physician for knee OA or pain during 2004-11. CONCLUSION Fifteen per cent of middle-aged or elderly individuals have knee OA and symptoms. About one in three of those do not consult a physician. Inefficient care of OA and self-coping may be an explanation.

Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide

BACKGROUND Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. OBJECTIVE To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. METHODS In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients). RESULTS Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. CONCLUSIONS Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

Effect of leisure time physical activity on severe knee or hip osteoarthritis leading to total joint replacement: a population-based prospective cohort study.

BackgroundStudies on leisure time physical activity as risk factor or protective factor for knee or hip osteoarthritis (OA) show divergent results. Longitudinal prospective studies are needed to clarify the association of physical activity with future OA. The aim was to explore in a prospective population-based cohort study the influence of leisure time physical activity on severe knee or hip OA, defined as knee or hip replacement due to OA.MethodsLeisure time physical activity was reported by 28320 participants (mean age 58 years (SD 7.6), 60% women) at baseline. An overall leisure time physical activity score, taking both duration and intensity of physical activities into account, was created. The most commonly reported activities were also used for analysis. The incidence of knee or hip replacement due to OA over 11 years was monitored by linkage with the Swedish hospital discharge register. Cox’s proportional hazards model (crude and adjusted for potential confounding factors) was used to assess the incidence of total joint replacement, or osteotomy (knee), in separate analyses of leisure time physical activity.ResultsThere was no significant overall association between leisure time physical activity and risk for knee or hip replacement due to OA over the 11-year observation time. For women only, the adjusted RR (95% CI) for hip replacement was 0.66 (0.48, 0.89) (fourth vs. first quartile), indicating a lower risk of hip replacement in those with the highest compared with the lowest physical activity. The most commonly reported activities were walking, bicycling, using stairs, and gardening. Walking was associated with a lower risk of hip replacement (adjusted RR 0.76 (95% CI 0.61, 0.94), specifically for women (adjusted RR 0.75 (95% CI 0.57, 0.98)).ConclusionsIn this population-based study of middle-aged men and women, leisure time physical activity showed no consistent overall relationship with incidence of severe knee or hip OA, defined as joint replacement due to OA, over 11 years. For women, higher leisure time physical activity may have a protective role for the incidence of hip replacement. Walking may have a protective role for hip replacement, specifically for women.

Genetic and environmental influence on lung function impairment in Swedish twins

BackgroundThe understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behaviour and the presence of respiratory symptoms has previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms.MethodsThe current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack years and respiratory symptoms.ResultsFully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men.ConclusionDifferences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.

Detection of COPD Exacerbations and Compliance With Patient-Reported Daily Symptom Diaries Using a Smartphone-Based Information System

Background Paper-based diaries and self-report of symptom worsening in COPD may lead to underdetection of exacerbations. Epidemiologically, COPD exacerbations exhibit seasonal patterns peaking at year-end. We examined whether the use of a BlackBerry-based daily symptom diary would detect 95% or more of exacerbations and enable characterization of seasonal differences among them. Methods Fifty participants with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I to IV COPD began a community-based study in December 2007. Another 30 began in December 2008. Participants transmitted daily symptom diaries using a BlackBerry. Alerts were triggered when symptom changes, missed diary transmissions, or medical care for a respiratory problem occurred. Participant encounters were initiated if COPD exacerbations were suspected. Participants used their BlackBerrys to report returns to normal breathing. Results Participants transmitted 99.9% of 28,514 possible daily diaries. All 191 (2.5/participant-year) COPD exacerbations meeting Anthonisen criteria were detected. During 148 of the 191 exacerbations (78%, 1.97/participant-year), patients were hospitalized and/or ordered prednisone, an antibiotic, or both. Respiratory viruses were detected in 78 of the 191 exacerbations (41%). Those coinciding with a respiratory viral infection averaged 12.0 days, and those without averaged 8.9 days (P < .04), with no difference in Anthonisen score. Respiratory symptom scores before exacerbations and after normal breathing return showed no differences. Exacerbations were more frequent during the Christmas period than the rest of the year but were not more frequent than in the rest of winter alone. Conclusions Smartphone-based collection of COPD symptom diaries enables near-complete identification of exacerbations at inception. Exacerbation rates in the Christmas season do not reach levels that necessitate changes in disease management.

Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome: Doubled Costs Compared with Patients with Asthma Alone☆

BACKGROUND Patients with asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have more rapid disease progression and more exacerbations than do those with either condition alone. Little research has been performed, however, in these patients. OBJECTIVE The objective was to summarize the health care utilization, costs, and comorbidities of patients with uncontrolled asthma and patients with ACOS. METHODS This retrospective analysis used medical and pharmacy claims from large commercial health plans. The study included patients 6 years or older with a diagnosis of asthma and one or more asthma exacerbation (index event). Patients were classified as having asthma alone or ACOS, and the two groups were matched for age, sex, region, index year, index month, and health plan type. Outcomes included rates of comorbid disease, health care utilization, and costs during the 12 months before and after the index exacerbation. RESULTS Among the matched patients with asthma (6,505 ACOS; 26,060 without COPD), mean annual all-cause health care costs were twice as high as for patients with ACOS (

Blood biomarkers and measures of pulmonary function-A study from the Swedish twin registry.

22,393 vs.

BP variability and cardiovascular autonomic function in relation to forced expiratory volume: a population-based study.

11,716; P < 0.0001). Asthma-related costs, representing 29% of total costs, were nearly twice as high among patients with ACOS (

Colds as predictors of the onset and severity of COPD exacerbations

6,319 vs. 3,356; P < 0.0001). Cost differences were driven by large differences in the proportions of patients with an inpatient hospitalization (34.0% vs. 14.6%; P < 0.0001) or emergency department visit (29.6% vs. 19.9%; P < 0.0001). Nearly all prespecified comorbid conditions were more prevalent in the ACOS group. CONCLUSIONS Patients with asthma and COPD had nearly double the health care costs as did patients with asthma without COPD. The overall disease profile of patients with asthma should be considered when managing patients, rather than treating asthma as a solitary condition.