The relation of adult bronchial responsiveness to serious childhood respiratory illness in the ECRHS

BACKGROUND: Respiratory symptoms in adulthood have been found to be associated with childhood respiratory infection, but few studies have analyzed adult bronchial responsiveness (BHR) with adequate adjustment for known risk factors. OBJECTIVE: To estimate the relation of BHR with serious childhood respiratory infections in a large population study. METHODS: The European Community Respiratory Health Survey (ECRHS) was a cross-sectional population-based survey in 34 centers. Data on serious respiratory infections before the age of 5 years and possible confounders were obtained from a questionnaire administered in the clinic. Blood samples were taken for measurement of total immunoglobulin E (IgE) and specific IgE to four common allergens, and spirometry and bronchial challenge with methacholine were performed. A continuous measure of BHR was analyzed by multiple regression, in 11,282 participants, in relation to serious respiratory infection and other potential risk factors, adjusted for center and major determinants of adult BHR. RESULTS: Those reporting a serious childhood respiratory infection had greater BHR, by an amount corresponding to approximately 0.23 doubling doses (95% confidence interval 0.02-0.44) of the amount of methacholine causing a 20% fall (PD(20)) in forced expiratory volume in 1s (FEV(1)). All childhood factors explained less than 0.3% of variation in BHR in addition to over 20% by factors measured in adulthood. The relation of BHR to BMI was confined to smokers. CONCLUSIONS: We found an effect of serious childhood respiratory infection on adult BHR, but this was small in comparison to relations of BHR to IgE-sensitization and airway caliber.     

Transportation of critically ill patients on extracorporeal membrane oxygenation

Serious pulmonary and cardiac failure may be treated with extracorporeal membrane oxygenation (ECMO) when conventional treatment fails. In some severely ill patients, it may be necessary to initiate ECMO at the local hospital and, thereafter, transport the patient back to the ECMO center. The aim of this study was to evaluate our experiences with transportation of patients on ECMO. From Oct 1992 to Jan 2008 23, patients were transported on ECMO from local hospitals to Rikshospitalet. The study included seventeen patients with pulmonary failure and four patients with cardiac failure. All age groups were represented. Aircraft were used in 17 cases, ground vehicles in six. The times from decision until ECMO was established, the time from ECMO to departure from the local hospital and the transportation time were registered. All transportations were uneventful. After 10.3 +/-6.7 days, six patients died on ECMO and another patient died within 30 days. Mean ECMO time for those who died was 13.3 +/- 9.6 vs. 8.5 +/- 4.7 days for survivors, p=0.34. Seventeen patients were able to be successfully weaned from ECMO. Thirty day survival was 67%. The mean age for survivors was 15.3+/-18.3 (range 0-54.6) vs. 23.6 +/- 20.3 years (range 0-55.9) in fatal cases, p=0.41. The time from referral to initiating ECMO was a mean of 7.32 +/- 2.3 (3.0-12.0) hours for survivors vs. 7.88 +/- 3.0 (3.50-13.40) hours for non- survivors, p=0.76. The time from initiating ECMO to departure was 5.1 +/- 6.5 (0.58-23.75) hours in survivors vs. 9.1 +/- 6.8 (0.55-18.45) hours in non-survivors, p=0.18. Time from departure to arrival at Rikshospitalet was a mean of 3.2 (0.50-5.10) hours for survivors versus 2.5 (0.5-4.40) for non-survivors, p=0.41. This study shows that ECMO can be successfully established at local hospitals, using an experienced team, and that transportation of patients on ECMO can be performed safely and without technical difficulties. Survival for this group of patients did not differ from patients treated at the ECMO center.     

Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II

BACKGROUND: Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated. METHODS: 5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg. RESULTS: Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups. CONCLUSIONS: These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association.     

The genetics of incontinence: A scoping review

The genetic causes underlying incontinence in both children and adults have begun to be unravelled during the last decades. The aim of this scoping review is to synthesize current knowledge on the genetics of childhood and adult urinary and faecal incontinence, identify similarities between different incontinence subgroups, and identify knowledge gaps to aid future research. PRISMA-ScR was used, and 76 studies were included. Early epidemiological family and twin studies suggest high heritability of incontinence. Linkage studies provide evidence for the existence of rare genetic variants; however, these variants have not been identified. Later candidate gene association studies and recent genome-wide association studies provide the first preliminary evidence that common risk variants also play a role. The genetics of incontinence in children and adults has predominantly been studied separately, but this review identifies for the first time the endothelin system as a potential common pathophysiological pathway. Overall, these findings strengthen the hypothesis that genetic variants play a prominent role in the pathogenesis of incontinence. Future research should include hypothesis-free studies of rare and common variants in large well-characterized cohorts with incontinence. Studies should include different age groups and ethnicities and both sexes to fully reveal the genetics of incontinence.     

The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months.

BACKGROUND: Most women with epilepsy need to take antiepileptic drugs (AEDs) in pregnancy to prevent the potentially harmful effects of seizures. Retrospective studies have demonstrated an increased chance of having a child with a birth defect (BD) in women with epilepsy taking AEDs. It is uncertain how much of this risk is directly caused by the AEDs and whether certain drugs or combinations are associated with a greater risk. AIMS: To establish a register to evaluate prospectively the incidence of adverse pregnancy outcomes in women exposed to specific AEDs; to determine whether certain AEDs or combinations were associated with a greater risk; and to determine whether other factors influenced the risk. METHODS: An Australia-wide, prospective, voluntary, telephone-interview based, observational register. Three groups of pregnant women were enrolled: those with epilepsy taking AEDs, those with epilepsy not taking AEDs, and those taking AEDs for a non-epileptic indication. The pregnancy outcomes were evaluated by follow-up interviews and by reference to hospital and treating doctors' records. RESULTS: Over the first 30 months of the study (till December 2001) 334 eligible women were enrolled, with all states and territories being represented. Two hundred and ninety two pregnancies had been completed, of which 256 (88%) resulted in a healthy live birth, 19 (6.5%) a live birth with a birth defect, four an induced abortion because of a detected malformation on ultrasound, one premature labour with a stillbirth and 12 (4%) spontaneous abortions. Of the completed pregnancies, 269 were exposed to at least one AED during the first trimester. The incidence of birth defects in relation to specific AEDs was: valproate (16.7%), phenytoin (10.5%), lamotrigine (7.7%) and carbamazepine (3.3%), none of which was significantly different from that in women with epilepsy not taking an AED (4.3%, n.s.). The dose of valproate taken was higher in pregnancies with BD compared to those without (mean 2081 mg vs. 1149 mg, p<0.0001). The incidence of folate supplementation being taken prior to conception did not differ for pregnancy outcomes with or without BD (70% vs. 66%, n.s.). CONCLUSIONS: The model for the Australian Pregnancy Register appears to be successful, with strong enrolment from all regions over the first 30 months. The study is prospective and includes reference to all new AEDs approved in Australia over the past decade. Analysis of the pregnancy outcomes to date may reveal early trends, but numbers are still to small for any definitive conclusions to be made regarding the relative risk in pregnancy of individual AEDs.     

Attenuated adrenergic responses to exercise in women with fibromyalgia – A controlled study

The pathogenesis of widespread pain and fibromyalgia (FM) is unknown. Altered responses from the hypothalamus–pituitary–adrenal axis, sympathetic nervous system and muscular system have been suggested as being of importance. The present study was undertaken to determine: (i) whether the sympathoadrenal response to repetitive isometric contractions until exhaustion is altered in patients with FM, and (ii) whether sympathoadrenal responses are associated with muscle fatigue and pain during exercise. Nineteen women with FM, and 19 healthy women matched for age, smoking and self‐reported physical activity, participated. Maximal voluntary contraction (MVC), repetitive isometric contractions (6s contraction and 4s resting phases) were performed with both quadriceps muscles at 30% of MVC until exhaustion. Muscle activity was recorded from the quadriceps muscles by surface electromyography (EMG). Plasma adrenalin (Adr), noradrenalin (NAdr) and cortisol were measured and perceived exertion and pain reported during exercise. Attenuated Adr responses (p<0.001) with normal plasma NAdr and cortisol (p>0.19) responses were found during exercise in the FM group compared with the control group. Significantly higher EMG amplitude (%EMG_max) during the contraction phases (p=0.001) was found in the FM than in the control group. Perceived exertion and pain responses to exercise were higher in the FM group than in the controls (p<0.001), without relationship to the sympathoadrenal responses. In conclusion; the exercise was perceived as being more painful and strenuous in the FM group. Muscle performance was altered with increased muscle activity during the exercise. Women with FM showed an attenuated Adr response to repetitive isometric exercise.