Vascular endothelial function assessed by flow-mediated vasodilatation in young adults born very preterm or with extremely low birthweight: A regional cohort study

Background: Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease in young adults. Endothelial dysfunction is established as an early marker for development of atherosclerotic cardiovascular disease. Previous studies of endothelial function in young adults born very preterm or with extremely low birthweight have, however, shown diverging results. Objective: We aimed to evaluate the risk of cardiovascular disease as measured by vascular endothelial function in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1,000 g), compared with term-born controls. Methods: This study included 50 young adults born very preterm or with extremely low birthweight and 49 term-born controls born in Norway in the periods 1982–1985, 1991–1992, and 1999–2000 at mean age 28 (±6) years. The endothelial function was assessed by ultrasound measured flow-mediated dilatation (FMD) of the right brachial artery. The arterial diameter was measured at baseline, after release of 5 min of occlusion, and after sublingual administration of nitroglycerine. FMD was reported as absolute and percentage diameter change from baseline and relative to nitroglycerine-induced dilatation. Results: The participants were mainly normal weight non-smokers, without hypertension, diabetes, or established cardiovascular disease. The cases and controls had mean blood pressure 112/71 (SD 12/9) and 112/69 (SD 11/8) mmHg, body mass index 24.0 (SD 4.2) and 24.4 (SD 4.5) kg/m2, and HbA1c 32.7 (SD 2.5) and 33.0 (SD 2.6) mmol/mol, respectively. For both groups, 4 (8%) were smokers. Mean FMD for the adults born very preterm or with extremely low birthweight was 0.17 mm (95% CI 0.14, 0.21) vs. 0.24 mm (95% CI 0.20, 0.28) for the controls (p = 0.01), corresponding to a percentage increase of 5.4% (95% CI 4.2, 6.6) and 7.6% (95% CI 6.2, 8.9), respectively (p = 0.02). The FMD relative to maximal nitroglycerine-induced dilatation was 20% and 31%, respectively (p = 0.001). Conclusions: Young adults born very preterm or with extremely low birthweight have significantly lower FMD compared with the term-born controls suggesting an increased risk of cardiovascular disease.publishedVersio

Exercise inducible laryngeal obstruction: diagnostics and management

SummaryObstruction of the central airways is an important cause of exercise-induced inspiratory symptoms (EIIS) in young and otherwise healthy individuals. This is a large, heterogeneous and vastly understudied group of patients. The symptoms are too often confused with those of asthma. Laryngoscopy performed as symptoms evolve during increasing exercise is pivotal, since the larynx plays an important role in symptomatology for the majority. Abnormalities vary between patients, and laryngoscopic findings are important for correct treatment and handling. The simplistic view that all EIIS is due to vocal cord dysfunction [VCD] still hampers science and patient management. Causal mechanisms are poorly understood. Most treatment options are based on weak evidence, but most patients seem to benefit from individualised information and guidance. The place of surgery has not been settled, but supraglottoplasty may cure well-defined severe cases. A systematic clinical approach, more and better research and randomised controlled treatment trials are of utmost importance in this field of respiratory medicine

Exercise inducible laryngeal obstruction: diagnostics and management

Obstruction of the central airways is an important cause of exercise-induced inspiratory symptoms (EIIS) in young and otherwise healthy individuals. This is a large, heterogeneous and vastly understudied group of patients. The symptoms are too often confused with those of asthma. Laryngoscopy performed as symptoms evolve during increasing exercise is pivotal, since the larynx plays an important role in symptomatology for the majority. Abnormalities vary between patients, and laryngoscopic findings are important for correct treatment and handling. The simplistic view that all EIIS is due to vocal cord dysfunction [VCD] still hampers science and patient management. Causal mechanisms are poorly understood. Most treatment options are based on weak evidence, but most patients seem to benefit from individualised information and guidance. The place of surgery has not been settled, but supraglottoplasty may cure well-defined severe cases. A systematic clinical approach, more and better research and randomised controlled treatment trials are of utmost importance in this field of respiratory medicine.publishedVersio

Long-term follow-up of self-reported mental health and health-related quality of life in adults born extremely preterm

Background Survival of extremely preterm (EP) birth is increasing, but long-term consequences are still largely unknown as their high survival rates are recent achievements. Aims To examine self-reported mental health, and health related quality of life (HRQoL) in a cohort of adults born EP in the early 1990s and individually matched term-born controls, and to describe development through the transition from teenager to adults. Methods Thirty-five eligible subjects were born at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g during 1991–1992 in this population-based cohort from Western Norway. We assessed mental health using Youth Self-Report (YSR) at 18 years of age, and Adult Self-Report (ASR) at 27 years, and HRQoL by RAND-36 at 27 years. Data were analysed by unadjusted and adjusted mixed effects models with time by group as interaction term. Results At 27 years, 24 (69 %) EP-born and 26 (74 %) term-born controls participated. Scores for internalising problems, and syndrome scale anxious/depressed and withdrawn were higher among EP-born compared to term-born controls. For HRQoL, scores were similar in EP-born and term-born groups, except the domain physical functioning where EP-born scored lower. Development over time from 18 to 27 years showed increasing (i.e. deteriorating) scores for internalising, anxious/depressed, somatic complaints, and attention problems in the EP born group. For the term-born, scores for anxious/depression increased over time. Conclusions At 27 years of age, EP-born adults reported more internalising problems than term-born controls, while HRQoL was relatively similar except physical functioning. Mental health problems in the EP-born increased from adolescence to adulthood.publishedVersio

Development of health-related quality of life and subjective health complaints in adults born extremely preterm: a longitudinal cohort study

Purpose To study development trajectories to 34 years of age of health-related quality of life (HRQoL) and subjective health complaints in extremely preterm (EP) born subjects with and without disability, and to compare with term-born controls. Methods A Norwegian longitudinal population-based cohort of subjects born in 1982–85 at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g and matched term-born controls completed the Norwegian version of the Short Form Health Survey-36 at ages 24 and 34 and the Health Behaviour in School-aged Children–Symptom Checklist at ages 17, 24 and 34 years. Data were analysed by unadjusted and adjusted mixed effects analyses with time by subject group as interaction term. Results A total of 35/49 (73%) surviving EP-born and 36/46 (78%) term-born controls participated at this third follow-up. EP-born subjects with severe disability reported clinical significant lower mean score in all domains compared to the term-born controls. Healthy EP-born subjects reported significantly lower mean scores for vitality, role emotional and mental health, and significantly higher mean score for total and psychological health complaints compared to term-born controls. There were no significant interactions with age regarding HRQoL and somatic health complaints, while there were significant differences in psychological health complaints; the EP-born scored higher at age 24 and lower at age 34. Conclusions EP-born adults at age 34 reported inferior HRQoL versus term-born peers, especially in the mental health domains, indicating that the negative differences observed at 24 years remained unchanged.publishedVersio

Symptoms and antecedents of autism in children born extremely premature: a national population-based study

The objective of this study is to investigate the prevalence of autism (ASD) symptoms, i.e. , social difficulties, repetitive behaviors, and communicational problems, among children born extremely preterm (EP) compared to a reference group, and to investigate possible antecedents of ASD symptoms among EP children. Method is a national Norwegian cohort of 11 year old EP children, excluding those with intellectual disabilities, non-ambulatory cerebral palsy, blindness, and/or deafness. Parents and teachers reported ASD symptoms using The Autism Spectrum Screening Questionnaire (ASSQ). Social difficulties, repetitive behaviors, communicational problems, and a total ASSQ score were presented. Combined ratings on the ASSQ was defined as parent and/or teacher scoring the child ≥ 98th percentile of the reference group, which was the population-based Bergen Child Study. Of eligible children, 216 (64%) EP and 1882 (61%) reference children participated. EP children had significantly higher mean scores and combined ratings on social difficulties (14.5% vs. 4.1%, OR: 3.2), repetitive behaviors (23.7% vs. 4.0%, OR: 6.4), communicational problems (23.1% vs. 4.8%, OR: 5.4), and the total ASSQ score (18.3% vs. 3.4%, OR: 5.7) compared to reference children. Only no prenatal steroids, IQ 70–84, and mental health problems at 5 years of age were significantly associated with ASD symptoms at 11 years of age. EP children were at increased risk of social difficulties, repetitive behaviors, and communicational problems, and approximately one out of five were reported as high scorers of ASD symptoms. No prenatal steroids use, IQ in the lower range, and mental health problems at 5 years of age were associated with ASD symptoms.publishedVersio

Exercise related respiratory problems in the young—Is it exercise-induced bronchoconstriction or laryngeal obstruction?

Complaints of breathlessness during heavy exercise is common in children and adolescents, and represent expressions of a subjective feeling that may be difficult to verify and to link with specific diagnoses through objective tests. Exercise-induced asthma and exercise-induced laryngeal obstruction are two common medical causes of breathing difficulities in children and adolescents that can be challenging to distinguish between, based only on the complaints presented by patients. However, by applying a systematic clinical approach that includes rational use of tests, both conditions can usually be diagnosed reliably. In this invited mini-review, we suggest an approach we find feasible in our everyday clinical work.publishedVersio

Conundrums in the breathless athlete; exercise-induced laryngeal obstruction or asthma?

Purpose: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are the two disorders commonly considered when athletes complain of exertional dyspnea. They are highly different but often confused. We aimed to address this diagnostic challenge and its consequences in elite athletes. Methods: We included all athletes competing at national or international level, referred to our institution for workup for EILO during 2013–2016. We diagnosed EILO from video-recorded laryngoscopy performed during maximal cardiopulmonary treadmill exercise (CLE test). Symptoms and previous diagnostic evaluations were obtained from referral letters and chart reviews. Results: Exercise-induced laryngeal obstruction was diagnosed in 73/101 referred athletes, of whom 70/73 had moderate/severe supraglottic obstruction and 3/73 had primarily glottic obstruction with only minor supraglottic involvement. Of the 73 athletes with EILO, we were able to identify objective tests for asthma in 55 participants, of whom 22 had findings supporting asthma. However, 58/73 had used asthma therapy at some time previously, with current use in 28. Only three reported that asthma medication had improved their exercise-related breathing problems, two of whom with tests confirming asthma. Treatment for EILO improved breathing problems in all but four. Conclusions: Objective testing verified EILO in most of the referred athletes. EILO coexisting with asthma was common, and large proportions had used asthma medication; however, few reported effect on exercise-related breathing problems. Unexplained persistent exertional dyspnea must not lead to indiscriminate escalation of asthma treatment, but instead incite investigation for EILO, either as a co-morbidity or as a differential diagnosis.publishedVersio

Early life growth and associations with lung function and bronchial hyperresponsiveness at 11-years of age

Low birthweight and being born small-for-gestational age (SGA) are linked to asthma and impaired lung function. Particularly, poor intrauterine growth followed by rapid catch-up growth during childhood may predispose for respiratory disease. Bronchial hyperresponsiveness (BHR) is an essential feature of asthma, but how foetal and early childhood growth are associated with BHR is less studied. Our hypothesis was that children born SGA or with accelerated early life growth have increased BHR and altered lung function at 11-years of age. We studied the associations between SGA and early childhood growth with lung function and BHR at 11-years of age in a subgroup of 468 children from the Norwegian Mother, Father and Child Cohort Study (MoBa), and included data from the Medical Birth Registry of Norway (MBRN). Weight at 6 months of age was positively associated with forced vital capacity (adjusted Beta: 0.121; 95% Confidence interval: 0.023, 0.219) and negatively associated with the ratio of forced expiratory flow in first second/forced vital capacity (−0.204; −0.317, −0.091) at 11-years of age. Similar patterns were found for weight at 36 months and for change in weight from birth to 6 months of age. SGA or other various variables of early childhood growth were not associated with BHR at 11-years of age. Early life growth was associated with an obstructive lung function pattern, but not with BHR in 11-year old children. Foetal growth restriction or weight gain during early childhood do not seem to be important risk factors for subsequent BHR in children.acceptedVersio

Exercise Training in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis

Objective: To evaluate the effects and safety of exercise training, and to determine the most effective exercise intervention for people with Duchenne muscular dystrophy. Exercise training was compared with no training, placebo or alternative exercise training. Primary outcomes were functioning and health-related quality of life. Secondary outcomes were muscular strength, endurance and lung function. Data sources: A systematic literature search was conducted in Medline, EMBASE, CINAHL, Cochrane Central, PEDro and Scopus. Study selection and data extraction: Screening, data extraction, risk of bias and quality assessment were carried out. Risk of bias was assessed using the Cochrane Collaborations risk of bias tools. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Data synthesis: Twelve studies with 282 participants were included. A narrative synthesis showed limited or no improvements in functioning compared with controls. Health-related quality of life was assessed in only 1 study. A meta-analysis showed a significant difference in muscular strength and endurance in favour of exercise training compared with no training and placebo. However, the certainty of evidence was very low. Conclusion: Exercise training may be beneficial in Duchenne muscular dystrophy, but the evidence remains uncertain. Further research is needed on exercise training to promote functioning and health-related quality of life in Duchenne muscular dystrophy.publishedVersio