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Objective Body temperature for a known ambient temperature is not known for infants born at term. We aimed to determine the normal range and the incidences of hypothermia and hyperthermia during the first 24 hours of life in healthy term-born infants nursed according to WHO recommendations.Design Prospective observational study.Setting Norwegian single centre district hospital. Infants were observed during skin-to-skin care or when dressed in cots.Participants Convenience sample of 951 healthy infants born at term.Methods Delivery room temperature was aimed at 26–30°C and rooming-in temperature at 24°C. We measured rectal and room temperatures at 2, 4, 8, 16 and 24 hours of age.Main outcome measures Percentile curves for rectal temperature. Proportions and risk factors for hypothermia and hyperthermia.Results The mean (SD) room temperature was 24.0°C (1.1), 23.8°C (1.0), 23.8°C (1.0)., 23.7°C (0.9) and 23.8°C (0.9). The median (2.5, 97.5 percentile) rectal temperature was 36.9°C (35.7–37.9), 36.8°C (35.9–37.5), 36.9°C (36.1–37.5), 37.0°C (36.4–37.7) and 37.1°C (36.5–37.7). Hypothermia (37.5°C) occurred in 12% and most commonly in large infants after 8 hours of life. Risk factors for hyperthermia were high birth weight (OR 2.2 (95% CI, 1.4 to 3.5), per kg), being awake, nursed skin to skin and being born through heavily stained amniotic fluid.Conclusions Term-born infants were at risk of hypothermia during the first hours after birth even when nursed in an assumed adequate thermal environment and at risk of hyperthermia after 8 hours of age.

BackgroundExercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, relevant to 5%–7% of young people. It is caused by paradoxical inspiratory adduction of laryngeal structures and diagnosed by continuous visualization of the larynx during high intensity exercise. Empirical data suggest that EILO consists of different subtypes that require different therapeutic approaches. Currently applied treatment approaches do not rest on randomized controlled trials (RCTs), and thus evidence-based guidelines cannot be established. This protocol describes the speech therapy treatment approach which is applied to EILO patients in a large prospective RCT called HelpILO.Methods and analysisConsenting patients consecutively diagnosed with EILO at Haukeland University Hospital are randomized into four treatment arms. Speech therapy is represented in two of these, provided in a structured manner based on general speech therapy principles and abdominal breathing, combined with experience obtained with these patients at our hospital during the last decades. The main outcome measure of HelpILO is changes of laryngoscopically visualized laryngeal adduction, rated at peak exercise before vs. after interventions, using a validated scoring system.Ethics and disseminationDespite widespread use of speech therapy in patients with EILO, this approach is insufficiently tested in RCTs, and the study is therefore considered ethically appropriate. The study will provide knowledge listed as a priority in a recent statement issued by major respiratory and laryngological societies and requested by clinicians and researchers engaged in this area. The results will be presented at relevant conferences, patient fora, and media platforms, and published in relevant peer reviewed international journals.

Introduction Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems. The current diagnostic approach rests on evaluation of laryngeal obstruction visualised by laryngoscopy performed continuously throughout a maximal exercise test (continuous laryngoscopy exercise (CLE) test) in patients who present with compatible symptoms. Laryngeal responses to high-intensity exercise in endurance athletes are not well described, potentially leading to inaccurate reference values and increasing the risk of misdiagnosing EILO.Aim To investigate laryngeal responses to high-intensity exercise in a healthy population of endurance athletes with no self-reported perception of respiratory problems.Methods A cross-sectional study was conducted at Haukeland University Hospital, Bergen, Norway, inviting amateur and professional athletes with no self-reported breathing problems who performed endurance training minimum four sessions weekly. Thirty-six eligible athletes completed a questionnaire detailing exercise habits and past and current respiratory symptoms. They performed a standardised CLE test from which cardiopulmonary exercise data and corresponding laryngeal responses were recorded. The CLE tests were evaluated in retrospect by two independent raters according to preset criteria providing a CLE score. The CLE score rates the severity of laryngeal obstruction during moderate and maximum exercise on the glottic and supraglottic regions on a scale ranging from 0 (no obstruction) to 3 (maximum obstruction).Results Twenty-nine (81%) athletes (15 females) aged 15–35 years completed a CLE test. Ten participants (33%) had a supraglottic CLE subscore of 2 or 3. Among these, two also had a glottic CLE subscore of 2 or 3. Notably, none had isolated glottic obstruction.Conclusion In healthy well-trained endurance athletes with no prior perception of respiratory symptoms, the laryngeal response to high-intensity exercise was diverse. Supraglottic laryngeal obstruction was observed in one-third of the athletes. The findings underline that a diagnosis of EILO should rest on observed laryngeal obstruction supported by compatible symptoms.

Introduction Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma.Methods and analysis The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80–120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up.Ethics and dissemination Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences.Trial registration number NCT04593394.

Abstract 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.

Abstract Background The use of psychotropics is high among the older population and may have detrimental effects on their physical and mental health. Cardiorespiratory fitness (CRF) is a strong and modifiable measure of health and declines with age. We aimed to study the association of change in CRF with use of psychotropics in community-dwelling older adults. Methods We analyzed longitudinal data from 1531 older adults from the Generation 100 study, aged 70–77 years at inclusion, and with a permanent address in Trondheim, Norway. Data on objectively measured peak oxygen uptake (VO2peak) were linked with register data from the Norwegian Prescription Database on prescribed psychotropics. The included psychotropics were antidepressants (N06A), antipsychotics (N05A), anxiolytics (N05B), hypnotics and sedatives (N05C), and N03AE (benzodiazepine derivatives). Analyses were done on any psychotropics as one group, and on the following separate groups: antidepressants (N06A), benzodiazepines (N05BA, N05CD, and N03AE), and z-hypnotics (N05CF). Peak oxygen uptake was measured four times over a five-year period and corresponding medication use was measured as defined daily doses (DDD). A random effects estimator was applied to investigate the association of change in VO2peak with the use of psychotropics. Results We found a statistically significant curvilinear association of change in VO2peak with use of any psychotropics and antidepressants. For VO2peak up to ~ 40 ml/kg/min, each 1 ml/kg/min increase was associated by a 3.3 DDD and 2.5 DDD decrease in use of any psychotropics and antidepressants, respectively. A bottoming-out effect was found and increases in VO2peak above ~ 40 ml/kg/min showed increased use of any psychotropics and antidepressants. However, the association of change in VO2peak with use was stronger for changes in the lower continuum of VO2peak levels and decreased with increasing VO2peak. No statistically significant association of change in VO2peak with use of benzodiazepines and z-hypnotics were found. However, because of a non-randomized design, we cannot rule out the possibility of confounding by indication. Conclusions The results of this study show a curvilinear association of change in VO2peak with use of any psychotropics and antidepressants in older adults. This relationship adds a new viewpoint on the adverse effects of psychotropic use and should be considered in interventions and policies aimed at reducing psychotropic medication use among the older population.

Introduction Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young adults. Current management generally consists of breathing advice, speech therapy, inspiratory muscle training or supraglottoplasty in highly motivated subjects with supraglottic collapse. Inhaled ipratropium bromide (IB) is a muscarinic receptor antagonist used to treat asthma that is suggested in a few reports to improve EILO symptoms. The aim of the present study was to investigate effects of inhaled IB in EILO diagnosed by continuous laryngoscopy exercise (CLE) test and classified by CLE scores. Methods A randomised crossover trial was conducted at Haukeland University Hospital, Bergen, Norway, enrolling participants diagnosed with EILO defined by characteristic symptoms and CLE score ≥3 (range 0–12). Two consecutive CLE tests were performed within 2 weeks, one test with and one test without prior administration of inhaled IB in a randomised order. Main outcomes were the CLE score, dyspnoea measured using a modified BORG scale (range 0–10) and cardiopulmonary exercise data provided by the CLE test. Results 20 participants (14 females) aged 12–25 years participated, and all ran to exhaustion on both tests. Mean CLE score, BORG score and peak oxygen consumption were similar in tests performed with and without IB; mean differences (95% confidence interval) were 0.08 (−0.28–0.43), 0.35 (−0.29–0.99) and −0.4 (−1.9–1.1) mL·kg−1·min−1, respectively. Conclusion Inhaled IB did not improve CLE score, dyspnoea or exercise capacity in subjects with EILO. The study does not support the use of inhaled IB to treat EILO.

Introduction Application of non-invasive positive airway pressure may provoke laryngeal responses that obstruct the airways, especially in patients with disturbed laryngeal control. To control and adjust for this, transnasal fibre-optic laryngoscopy (TFL) is used to visualise laryngeal movements during therapeutic interventions. Being an invasive procedure, this may be unpleasant for patients. The aim of this study is to evaluate if ultrasound (US) imaging of the larynx may be used as an alternative less invasive diagnostic tool for evaluating the upper airway responses to non-invasive ventilation (NIV) and mechanical insufflation–exsufflation (MI-E).Methods and analysis This protocol presents an experimental cross-sectional study of a novel method to study laryngeal responses in adult healthy volunteers (n=30). The participants will be assessed with simultaneous TFL and laryngeal US imaging (anterior and lateral approaches) during NIV and MI-E therapy. Additionally, airflow and pressure signals will be registered during the procedures. The primary outcome is whether laryngeal US is a feasible method to study laryngeal responses and, if so, to compare the laryngeal responses visualised with TFL and US. The participants’ perception of the examinations will be recorded. Secondary outcomes include airflow curve shapes and calculated ventilation volumes during the interventions.Ethics and dissemination The study has been approved by The Regional Committee for Medical Research Ethics in Norway, and registered in ClinicalTrials.gov. Results will be disseminated through peer-reviewed journals, presentation of scientific abstracts at international medical conventions and oral presentations in relevant medical conventions.Trial registration number NCT04586855.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts to understand the pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding the cell type-specific cytopathology and its impact on cellular tropism. Furthermore, the impact of novel SARS-CoV-2 mutations on cellular tropism, alternative routes of entry, the impact of co-infections, and virus replication kinetics along the respiratory tract remains to be explored in improved models. Most applied virology models are not well suited to address the remaining questions, as they do not recapitulate the histoarchitecture and cellular composition of human respiratory tissues. The overall aim of this work was to establish from single biopsy specimens, a human adult stem cell-derived organoid model representing the upper respiratory airways and lungs and explore the applicability of this model to study respiratory virus infection. First, we characterized the organoid model with respect to growth pattern and histoarchitecture, cellular composition, and functional characteristics. Next, in situ expression of viral entry receptors, including influenza virus-relevant sialic acids and SARS-CoV-2 entry receptor ACE2 and TMPRSS2, were confirmed in organoids of bronchiolar and alveolar differentiation. We further showed successful infection by pseudotype influenza A H7N1 and H5N1 virus, and the ability of the model to support viral replication of influenza A H7N1 virus. Finally, successful infection and replication of a clinical isolate of SARS-CoV-2 were confirmed in the organoids by TCID50 assay and immunostaining to detect intracellular SARS-CoV-2 specific nucleocapsid and dsRNA. The prominent syncytia formation in organoid tissues following SARS-CoV-2 infection mimics the findings from infected human tissues in situ. We conclude that the human organotypic model described here may be particularly useful for virology studies to evaluate regional differences in the host response to infection. The model contains the various cell types along the respiratory tract, expresses respiratory virus entry factors, and supports successful infection and replication of influenza virus and SARS-CoV-2. Thus, the model may serve as a relevant and reliable tool in virology and aid in pandemic preparedness, and efficient evaluation of antiviral strategies.

Objective Exercise-induced laryngeal obstruction is an important cause of exertional dyspnoea. The diagnosis rests on visual judgement of relative changes of the laryngeal inlet during continuous laryngoscopy exercise (CLE) tests, but we lack objective measures that reflect functional consequences. We aimed to investigate repeatability and normal values of translaryngeal airway resistance measured at maximal intensity exercise. Methods 31 healthy nonsmokers without exercise-related breathing problems were recruited. Participants performed two CLE tests with verified positioning of two pressure sensors, one at the tip of the epiglottis (supraglottic) and one by the fifth tracheal ring (subglottic). Airway pressure and flow data were continuously collected breath-by-breath and used to calculate translaryngeal resistance at peak exercise. Laryngeal obstruction was assessed according to a standardised CLE score system. Results Data from 26 participants (16 females) with two successful tests and equal CLE scores on both test sessions were included in the translaryngeal resistance repeatability analyses. The coefficient of repeatability (CR) was 0.62 cmH2O·L−1·s−1, corresponding to a CR% of 21%. Mean±sd translaryngeal airway resistance (cmH2O·L−1·s−1) in participants with no laryngeal obstruction (n=15) was 2.88±0.50 in females and 2.18±0.50 in males. Higher CLE scores correlated with higher translaryngeal resistance in females (r=0.81, p

Abstract Background Current demographic changes affect both the level and composition of health and care needs in the population. The aim of this study was to estimate utilisation and cost for a comprehensive range of health and care services by age and gender to provide an in-depth picture of the life-span pattern of service needs and related costs. Methods Data on service use in 2010 for the entire population in Norway were collected from four high-quality national registers. Cost for different services were calculated combining data on service utilisation from the registries and estimates of unit cost. Data on cost and users were aggregated within four healthcare services and seven long-term care services subtypes. Per capita cost by age and gender was decomposed into user rates and cost per user for each of the eleven services. Results Half of the population is under 40 years of age, but only a quarter of the health and care cost is used on this age group. The age-group of 65 or older, on the other hand, represent only 15% of the population, but is responsible for almost half of the total cost. Healthcare cost dominates in ages under 80 and mental health services dominates in adolescents and young adults. Use of other healthcare services are high in middle aged and elderly but decreases for the oldest old. Use of care services and in particular institutional care increases in old age. Healthcare cost per user follows roughly the same age pattern as user rates, whereas user cost for care services typically are either relatively stable or decrease with age among adults. Gender differences in the age pattern of health and care costs are also revealed and discussed. Conclusion The type of services used, and the related cost, show a clear life-span as well as gender pattern. Hence, population aging and narrowing gender-gap in longivety calls for high policy awarness on changing health and care needs. Our study also underscores the need for an attentive and pro-active stance towards the high service prevalence and high cost of mental health care in our upcoming generations.

Abstract Background While the majority of deaths in high-income countries currently occur within institutional settings such as hospitals and nursing homes, there is considerable variation in the pattern of place of death. The place of death is known to impact many relevant considerations about death and dying, such as the quality of the dying process, family involvement in care, health services design and health policy, as well as public versus private costs of end-of-life care. The objective of this study was to analyse how the availability and capacity of publicly financed home-based and institutional care resources are related to place of death in Norway. Methods This study utilized a dataset covering all deaths in Norway in the years 2003–2011, contrasting three places of death, namely hospital, nursing home and home. The analysis was performed using a multilevel multinomial logistic regression model to estimate the probability of each outcome while considering the hierarchical nature of factors affecting the place of death. The analysis utilized variation in health system variables at the local community and hospital district levels. The analysis was based on data from two public sources: the Norwegian Cause of Death Registry and Statistics Norway. Results Hospital accessibility, in terms of short travel time and hospital bed capacity, was positively associated with the likelihood of hospital death. Higher capacity of nursing home beds increased the likelihood of nursing home death, and higher capacity of home care increased the likelihood of home death. Contrasting three alternative places of death uncovered a pattern of service interactions, wherein hospital and home care resources together served as an alternative to end-of-life care in nursing homes. Conclusions Norway has a low proportion of home deaths compared with other countries. The proportion of home deaths varies between local communities. Increasing the availability of home care services is likely to enable more people to die at home, if that is what they prefer.

BackgroundExercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high-intensity exercise. Empirical data suggest that EILO consists of different subtypes, possibly requiring different therapeutic approaches. Currently applied treatments do not rest on randomized controlled trials, and international guidelines based on good evidence can therefore not be established. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO.Methods and AnalysisConsenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four non-invasive treatment arms, based on promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the non-invasive approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimally invasive laser supraglottoplasty or (G) no surgery. Power calculations are based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions.Ethics and DisseminationThe study will assess approaches to EILO treatments that despite widespread use, are insufficiently tested in structured, verifiable, randomized, controlled studies, and is therefore considered ethically sound. The study will provide knowledge listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5–7% of young people. Dissemination will occur in peer-reviewed journals, at relevant media platforms and conferences, and by engaging with patient organizations and the healthcare bureaucracy.

Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses.Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term.Methods: Adults born EP (

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.

When the ability to cough is impaired, secretion clearance may be assisted and augmented by Mechanical Insufflation-Exsufflation (MI-E) treatment. In patients with Amyotrophic Lateral Sclerosis, the efficacy of MI-E may be hampered by counterproductive upper airway responses. Careful adjustment of MI-E settings can be beneficial. During the disease progression, a 41-year-old woman with bulbar Amyotrophic Lateral Sclerosis experienced that treatment with MI-E was exhausting and inefficient. Despite adjustments of settings, all treatment led to retching. A change of MI-E device led to more effective treatment. A bench test revealed variations in flow and pressure waveforms in the two devices. When MI-E treatment fails, differences in equipment delivery need to be considered in addition to the adjustment of MI-E settings.

Abstract Exercise‐induced laryngeal obstruction (EILO) is common, but we lack readily available diagnostic tools. The larynx represents an important point of resistance in the airways, and we therefore hypothesized that EILO is associated with characteristic breathing patterns possible to record from a standard incremental ergospirometry test. We studied 24 individuals with moderate/severe EILO and 20 individuals with no‐EILO, mean (SD) age 17 (6.1) and 24 (6.4) years, respectively. EILO versus no‐EILO was verified from maximal continuous laryngoscopy treadmill exercise (CLE) tests, which also included ergospirometry. We described the relationships between minute ventilation (V˙E) versus tidal volume (VT) and V˙E versus carbon dioxide output (V˙CO2), using respectively quadratic and linear equations, and applied adjusted regression models to compare ergospirometry data and curve parameters. Compared to the no‐EILO group, the group with EILO had prolonged inspiratory time (Tin), lower breathing frequency (Bf), lower V˙E, and lower inspiratory flow rate (V˙in) at peak exercise. Mathematical modeling of the breathing pattern relationships was feasible in both groups, with similar coefficients of variation. For V˙E versus VT, the mathematical curve parameters were similar. For V˙E versus V˙CO2, the slope was similar but the intercept was lower in the EILO group. EILO was associated with prolonged Tin, lower Bf, V˙E, and V˙E. The relationship between V˙E versus VT was similar, whereas for V˙E versus V˙CO2, the slope was almost parallel but shifted downward for the EILO group. Most ergospirometry data overlapped, except V˙in which discriminated between EILO and no‐EILO in a promising way.

Background: Exercise-induced laryngeal obstruction (EILO) is common in young people with exertional breathing difficulties. Psychological characteristics have been proposed as underlying contributors; however, the evidence for this is limited.Objectives: Describe self-reported health, self-efficacy, and anxiety symptoms in adolescents with EILO, and address possible associations with EILO subtypes and severity.Methods: Cross-sectional study of 71/180 (39%) adolescents tested for EILO at Haukeland University Hospital during 2014–2016, age range 14–18 years. Validated questionnaires were used to assess general self-rated health, subjective health complaints (Health Behavior in School-aged Children-Symptom Check List; HBSC-SCL), general self-efficacy (GSE), and anxiety symptoms (SCARED). The outcomes were compared with normative data from comparable unselected populations.Results: The HBSC-SCL items for somatic complaints revealed weekly or more often occurrence of headache in 42%, abdominal pain in 30%, backache in 31%, and dizziness in 32%. For psychological complaints, corresponding figures were 26% for feeling low, 43% for irritability or bad mood, 33% for feeling nervous, and 38% for sleep problems. Mean (range) GSE score was 3.13 (2.2–4.0), and reports suggesting anxiety symptoms were rare. The outcomes were in line with normative data from comparable unselected populations. Self-rated health, and scores obtained for HBSC-SCL, GSE, and SCARED were similarly distributed across EILO subtypes and severity.Conclusion: Self-reported health, self-efficacy, and level of anxiety symptoms in adolescents with laryngoscopically confirmed EILO were similar to data obtained in comparable unselected populations, irrespective of EILO subtype and severity. The findings challenge the notion that pediatric EILO is causally related to psychological problems.

Abstract Patient‐derived organoids have revolutionized biomedical research and therapies by "transferring the patient into the Petri dish". In vitro access to human lung organoids representing distal lung tissue, i.e. alveolar organoids, would facilitate research pertaining to a wide range of medical conditions and might open for a future approach to individualized treatment.We propose a protocol to derive a single human lung biopsy towards both alveolar and bronchiolar organoids. By modulating Wnt pathway, we obtained a differential gene expression of the main markers for both subtypes, such as a higher expression of surfactant protein C in alveolar organoids or a higher expression of mucine 5AC in bronchiolar organoids. Although the specific cell enrichment was not complete, the differentiation was observed as early as passage 1 based on morphology, and confirmed by QPCR and histology at passage 2. These results are consistent with a functional specification of lung epithelium towards both alveoli‐ and bronchi‐enriched organoids from first passages

Aims A cardiopulmonary exercise test (CPET) is the gold standard to evaluate symptom-limiting exercise intolerance, while continuous laryngoscopy performed during exercise (CLE) is required to diagnose exercise-induced laryngeal obstruction. Combining CPET with CLE would save time and resources; however, the CPET data may be distorted by the extra equipment. We therefore aimed to study whether CPET with CLE influences peak oxygen uptake (V′O2peak) and other gas exchange parameters when compared to a regular CPET. Methods Forty healthy athletes without exercise-related breathing problems, 15–35 years of age, performed CPET to peak exercise with and without an added CLE set-up, in randomised order 2–4 days apart, applying an identical computerised treadmill protocol. Results At peak exercise, the mean difference (95% confidence interval) between CPET with and without extra CLE set-up for V′O2peak, respiratory exchange ratio (RER), minute ventilation (V′E) and heart rate (HR) was 0.2 (−0.4 to 0.8) mL·kg−1·min−1, 0.01(−0.007 to 0.027) units, 2.6 (−1.3 to 6.5) L·min−1 and 1.4 (−0.8 to 3.5) beats·min−1, respectively. Agreement (95% limits of agreement) for V′O2peak, RER and V′E was 0.2 (±3.7) mL·kg−1·min−1, 0.01 (±0.10) units and 2.6 (±24.0) L·min−1, respectively. No systematic or proportional bias was found except for the completed distance, which was 49 m (95% CI 16 to 82 m) longer during CPET. Conclusion Parameters of gas exchange, including V′O2peak and RER, obtained from a maximal CPET performed with the extra CLE set-up can be used interchangeably with data obtained from standard CPET, thus preventing unnecessary additional testing.

Objectives: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0–10 years, 10–18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. Results: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function.

Objective: To investigate voice characteristics and exercise related respiratory symptoms in extremely preterm born 11-year-old children, focusing particularly on associations with management of a patent ductus arteriosus (PDA).Study design: Prospective follow-up of all children born in Norway during 1999–2000 at gestational age

Abstract Background Equitable access to health services is a key ingredient in reaching health for persons with disabilities and other vulnerable groups. So far, research on access to health services in low- and middle-income countries has largely relied on self-reported survey data. Realizing that there may be substantial discrepancies between perceived and actual access, other methods are needed for more precise knowledge to guide health policy and planning. The objective of this article is to describe and discuss an innovative methodological triangulation where statistical and spatial analysis of perceived distance and objective measures of access is combined with qualitative evidence. Methods The data for the study was drawn from a large household and individual questionnaire based survey carried out in Namibia and Malawi. The survey data was combined with spatial data of respondents and health facilities, key informant interviews and focus group discussions. To analyse access and barriers to access, a model is developed that takes into account both measured and perceived access. The geo-referenced survey data is used to establish four outcome categories of perceived and measured access as either good or poor. Combined with analyses of the terrain and the actual distance from where the respondents live to the health facility they go to, the data allows for categorising areas and respondents according to the four outcome categories. The four groups are subsequently analysed with respect to variation in individual characteristics and vulnerability factors. The qualitative component includes participatory map drawing and is used to gain further insight into the mechanisms behind the different combinations of perceived and actual access. Results Preliminary results show that there are substantial discrepancies between perceived and actual access to health services and the qualitative study provides insight into mechanisms behind such divergences. Conclusion The novel combination of survey data, geographical data and qualitative data will generate a model on access to health services in poor contexts that will feed into efforts to improve access for the most vulnerable people in underserved areas.

Abstract Background School non-completion and early work disability is a great public health challenge in Norway, as in most western countries. This study aims to investigate how medically based disability pension (DP) among young adults varies geographically and how municipal socioeconomic conditions interact with non-completion of secondary education in determining DP risk. Methods The study includes a nationally representative sample of 30% of all Norwegians (N = 350,699) aged 21–40 in 2010 from Statistic Norway’s population registries. Multilevel models incorporating factors at the individual, neighbourhood and municipal levels were applied to estimate the neighbourhood and municipality general contextual effects in DP receipt, and detect possible differences in the impact of municipal socioeconomic conditions on DP risk between completers and non-completers of secondary education. Results A pattern of spatial clustering at the neighbourhood (ICC = 0.124) and municipality (ICC = 0.021) levels are clearly evident, indicating that the underlying causes of DP receipt have a systematic neighbourhood and municipality variation in Norway. Non-completion of secondary education is strongly correlated with DP receipt among those younger than 40. Socioeconomic characteristics of the municipality are also significantly correlated with DP risk, but these associations are conditioned by the completion of secondary education. Living in a socioeconomically advantageous municipality (i.e. high income, high education levels and low unemployment and social security payment rates) is associated with a higher risk of DP, but only among those who do not complete their secondary education. Although the proportion of DPs was equal in rural and urban areas, it is evident that young people living in urban settings are more at risk of early DP than their counterparts living in rural parts of the country when controlling for other risk factors. Conclusion The association between school non-completion and DP risk varies between municipalities and local socioeconomic environments. The interplay between personal characteristics and the local community is important in DP risk among young adults, implying that preventive measures should be directed not only at the individual level, but also include the educational system and the local community.

Abstract Background Advances in perinatal care have markedly increased the prospects of survival for infants born extremely preterm (EP). The aim of this study was to investigate hospitalisation rates and respiratory morbidity from five to 11 years of age in a prospective national cohort of EP children born in the surfactant era. Methods This was a national prospective cohort study of all children born in Norway during 1999 and 2000 with gestational age (GA)

Central to this article is the issue of choosing sites for where a fieldwork could provide a better understanding of divergences in health care accessibility. Access to health care is critical to good health, but inhabitants may experience barriers to health care limiting their ability to obtain the care they need. Most inhabitants of low-income countries need to walk long distances along meandering paths to get to health care services. Individuals in Malawi responded to a survey with a battery of questions on perceived difficulties in accessing health care services. Using both vertical and horizontal impedance, we modelled walking time between household locations for the individuals in our sample and the health care centres they were using. The digital elevation model and Tobler’s hiking function were used to represent vertical impedance, while OpenStreetMap integrated with land cover map were used to represent horizontal impedance. Combining measures of walking time and perceived accessibility in Malawi, we used spatial statistics and found spatial clusters with substantial discrepancies in health care accessibility, which represented fieldwork locations favourable for providing a better understanding of barriers to health access.

Background Exercise-induced laryngeal obstruction (EILO) is common in athletes and presents with dyspnoea, chest tightness, inspiratory stridor and sometimes panic reactions. The evidence for conservative treatment is weak, but case reports suggest effects from inspiratory muscle training (IMT). We aimed to explore effects from IMT used in athletes with EILO.Method Twenty-eight athletes, mean age 16.4 years, diagnosed with EILO at our clinic, participated in a 6-week treatment programme, using a resistive flow-dependent IMT device (Respifit S). Four athletes competed at international level, 13 at national and 11 at regional levels. Video-recorded continuous transnasal flexible laryngoscopy was performed from rest to peak exercise (continuous laryngoscopy exercise (CLE) test) and scored before and 2–4 weeks after the training period. Ergospirometric variables were obtained from this CLE set-up. Lung function was measured according to guidelines. Symptom scores and demographic variables were obtained from a questionnaire.Results After the treatment period, symptoms had decreased in 22/28 (79%) participants. Mean overall CLE score had improved after treatment (p

Dynamic obstructions of the larynx are a set of disorders that occur during exercise in equines and humans. There are a number of similarities in presentation, diagnosis, pathophysiology and treatment. Both equines and humans present with exercise intolerance secondary to dyspnea. During laryngoscopy at rest, the larynx appears to function normally. Abnormalities are only revealed during laryngoscopy at exercise, seemingly triggered by increased ventilatory demands, and quickly resolve after cessation of exercise. Lower airway disease (asthma being the most prevalent condition), cardiac disease and lack of fitness are the major differentials in both species. Laryngoscopic examination during exercise should be performed from rest to peak exertion to allow for a comprehensive diagnosis, including where the airway collapse begins, and thereafter how it progresses. Dynamic disorders with most visual similarity between humans and equines are: aryepiglottic fold collapse (both species); equine dynamic laryngeal collapse (DLC) relative to some forms of human combined supraglottic/glottic collapse; and epiglottic retroversion (both species). Quantitative grading techniques, such as airway pressure measurement, that have proven effective in veterinary research are currently being piloted in human studies. Conditions that appear visually similar are treated in comparable ways. The similarities of anatomy and certain types of dynamic collapse would suggest that the equine larynx provides a good model for human upper respiratory tract obstruction during exercise. Thus, close collaboration between veterinarians and medical personal may lead to further advancements in understanding pathophysiologic processes, and enhance the development of improved diagnostic tests and treatments that will benefit both species.

Introduction: Exercise induced laryngeal obstruction (EILO) is relatively common in adolescents, with symptoms often confused with exercise induced asthma. EILO often starts with medial or inward rotation of supraglottic structures of the larynx, whereas glottic adduction appears as a secondary phenomenon in a majority. Therefore, surgical treatment (supraglottoplasty) is used in thoroughly selected and highly motivated patients with pronounced symptoms and severe supraglottic collapse.Aim: To investigate efficacy and safety of laser supraglottoplasty as treatment for severe supraglottic EILO by retrospective chart reviews.Methods: The EILO register at Haukeland University Hospital, Bergen, Norway was used to identify patients who had undergone laser supraglottoplasty for severe supraglottic EILO, verified by continuous laryngoscopy exercise (CLE) test, during 2013–2015. Laser incision in both aryepiglottic folds anterior to the cuneiform tubercles and removal of the mucosa around the top was performed in general anesthesia. Outcomes were questionnaire based self-reported symptoms, and laryngeal obstruction scored according to a defined scheme during a CLE-test performed before and after surgery.Results: Forty-five of 65 eligible patients, mean age 15.9 years, were included. Post-operatively, 38/45 (84%) patients reported less symptoms, whereas CLE-test scores had improved in all, of whom 16/45 (36%) had no signs of obstruction. Most improvements were at the supraglottic level, but 21/45 (47%) also improved at the glottic level. Two of 65 patients had complications; self-limiting vocal fold paresis and scarring/shortening of plica ary-epiglottica.Conclusion: Supraglottoplasty improves symptoms and decreases laryngeal obstruction in patients with severe supraglottic EILO, and appears safe in highly selected cases.

Objective: Prematurely born children have been reported to have more sleep problems throughout childhood than children born at term. The aim of this study was to explore if prenatal or neonatal factors can predict sleep problems at age 11 years in children born extremely preterm (EPT).Method: A prospective observational study of all infants who were born EPT in Norway in 1999 and 2000. Prenatal and neonatal data were collected by all Norwegian obstetric and pediatric departments. Parental questionnaire mapped sleep problems and sleep habits at the age of 11 years.Results: Of the 372 eligible children, 221 participated. Of those, 28.1% snored, 27.5% had difficulty falling asleep or frequent awakenings and 17.2% suffered from daytime sleepiness. The mean sleep duration was 9.4 h (range 4.3–11.0 h). Smoking in pregnancy predicted snoring (odds ratio 4.3). Neonatal cerebral hemorrhage and being born small for gestational age predicted difficulty falling asleep or frequent awakenings (odds ratio 2.2 and 2.3). Other morbidities during pregnancy or the newborn period, gestational age or the burden of treatment in the neonatal intensive care unit did not predict sleep problems. None of the studied prenatal or neonatal factors predicted daytime sleepiness or sleep duration

Early prediction of bronchopulmonary dysplasia (BPD) may facilitate tailored management for neonates at risk. We investigated whether easily accessible flow data from a mechanical ventilator can predict BPD in neonates born extremely premature (EP). In a prospective population-based study of EP-born neonates, flow data were obtained from the ventilator during the first 48 h of life. Data were logged for >10 min and then converted to flow–volume loops using custom-made software. Tidal breathing parameters were calculated and averaged from ≥200 breath cycles, and data were compared between those who later developed moderate/severe and no/mild BPD. Of 33 neonates, 18 developed moderate/severe and 15 no/mild BPD. The groups did not differ in gestational age, surfactant treatment or ventilator settings. The infants who developed moderate/severe BPD had evidence of less airflow obstruction, significantly so for tidal expiratory flow at 50% of tidal expiratory volume (TEF50) expressed as a ratio of peak tidal expiratory flow (PTEF) (p=0.007). A compound model estimated by multiple logistic regression incorporating TEF50/PTEF, birthweight z-score and sex predicted moderate/severe BPD with good accuracy (area under the curve 0.893, 95% CI 0.735–0.973). This study suggests that flow data obtained from ventilators during the first hours of life may predict later BPD in premature neonates. Future and larger studies are needed to validate these findings and to determine their clinical usefulness.

BACKGROUND:Preterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life. AIMS:We tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood. METHODS:At 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age-GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao. RESULTS:Fifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p0.2) and did not differ between the groups. CONCLUSIONS:Children born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors.

Individuals reporting episodes of breathing problems caused by re-occurring variable airflow obstructions in the larynx have been described in an increasing number of publications, with more than 40 different terms being used without consensus on definitions. This lack of an international consensus on nomenclature is a serious obstacle for the development of the area, as knowledge from different centres cannot be matched, pooled or readily utilised by others. Thus, an international Task Force has been created, led by the European Respiratory Society/European Laryngological Society/American College of Chest Physicians. This review describes the methods used to reach an international consensus on the subject and the resulting nomenclature, the 2013 international consensus conference nomenclature.

Purpose: Children and adolescents born extremely preterm (EP) have lower dynamic lung volumes and gas transfer capacity than subjects born at term. Most studies also report lower aerobic capacity. We hypothesized that ventilatory efficiency was poorer and that breathing patterns differed in EP−born compared to term−born individuals.Methods: Two area−based cohorts of participants born with gestational age ≤28 weeks or birth weight ≤1000 g in 1982−85 (n = 46) and 1991–92 (n = 35) were compared with individually matched controls born at term. Mean ages were 18 and 10 years, respectively. The participants performed an incremental treadmill exercise test to peak oxygen uptake with data averaged over 20 s intervals. For each participant, the relationship between exhaled minute ventilation (V˙E) and carbon dioxide output (V˙CO2) was described by a linear model, and the relationship between tidal volume (VT) and V˙E by a quadratic model. Multivariate regression analyses were done with curve parameters as dependent variables, and the categories EP vs. term−born, sex, age, height, weight and forced expiratory volume in 1 s (FEV1) as independent variables.Results: In adjusted analyses, the slope of the V˙E−V˙CO2 relationship was significantly steeper in the EP than the term-born group, whereas no group difference was observed for the breathing pattern, which was related to FEV1 only.Conclusion: EP-born participants breathed with higher V˙E for any given CO2 output, indicating lower ventilatory efficiency, possibly contributing to lower aerobic capacity. The breathing patterns did not differ between the EP and term−born groups when adjusted for FEV1.

[This corrects the article DOI: 10.1371/journal.pone.0172281.].

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p

BACKGROUND:Completion of secondary education is important for individuals' future health and health behaviour. The fundamental purpose of this study is to investigate the variation and clustering of school completion in families and neighbourhoods. Secondly, we aim to examine the impact of individuals' family structure and neighbourhood of residence and examine to what extent parental education level moderates these associations. METHODS:Longitudinal register data for 30% of the entire Norwegian population aged 21-27 years in 2010 (N = 107,003) was extracted from Statistic Norway´s event database. Three-level logistic regression models, which incorporated individual, family, and neighbourhood contextual factors, were applied to estimate the family and neighbourhood general contextual effects and detect possible educational differences in the impact of family structure and urban place of residence in school completion. RESULTS:Completion rates were significantly higher within families with higher education level (79% in tertiary educated families vs. 61% and 48% in secondary and primary educated families respectively) and were strongly correlated within families (ICC = 39.6) and neighbourhoods (ICC = 5.7). Several structural factors at the family level negatively associated with school completion (e.g., family disruption, large family size, and young maternal age) were more prevalent and displayed more negative impact among primary educated individuals. Urban residence was associated with school completion, but only among the tertiary educated. CONCLUSIONS:Investment in the resources in the individuals' immediate surroundings, including family and neighbourhood, may address a substantial portion of the social inequalities in the completion of upper secondary education. The high intra-familial correlation in school completion suggests that public health policies and future research should acknowledge family environments in order to improve secondary education completion rates among young people within lower educated families.

Reliable, accurate and noninvasive methods for measuring lung function in infants are desirable. Electromagnetic inductance plethysmography has been used to perform infant spirometry and VoluSense Pediatrics (VSP) (VoluSense, Bergen, Norway) represents an updated version of this technique. We aimed to examine its accuracy compared to a validated system measuring airflow via a facemask using an ultrasonic flowmeter. We tested 30 infants with postmenstrual ages between 36 to 43 weeks and weights from 2.3 to 4.8 kg, applying both methods simultaneously and applying VSP alone. Agreement between the methods was calculated using Bland–Altman analyses and we also estimated the effect of applying the mask. Mean differences for all breathing parameters were within ±5.5% and limits of agreement between the two methods were acceptable, except perhaps for peak tidal expiratory flow (PTEF). Application of the facemask significantly increased tidal volume, minute ventilation, PTEF, the ratio of inspiratory to expiratory time and the ratio of expiratory flow at 50% of expired volume to PTEF. VSP accurately measured tidal breathing parameters and seems well suited for tidal breathing measurements in infants under treatment with equipment that precludes the use of a facemask.

Background: Androgen receptor (AR) and the phosphatidylinositol-3 kinase (PI3K) signaling are two of the most important pathways implicated in prostate cancer. Previous work has shown that there is crosstalk between these two pathways; however, there are conflicting findings and the molecular mechanisms are not clear. Here we studied the AR–PI3K pathway crosstalk in prostate cancer cells in vitro as well as in vivo.

Background. Knowledge of long-term health related outcomes in contemporary populations born extremely preterm (EP) is scarce. We aimed to explore developmental trajectories of health-related quality of life (HRQoL) and behavior from mid-childhood to early adulthood in extremely preterm and term-born individuals.Methods. Subjects born at gestational age ≤28 weeks or with birth weight ≤1,000 g within a region of Norway in 1991–92 and matched term-born control subjects were assessed at 10 and 18 years. HRQoL was measured with the Child Health Questionnaire (CHQ) and behavior with the Child Behavior Checklist (CBCL), using parent assessment at both ages and self-assessment at 18 years.Results. All eligible EP (n = 35) and control children participated at 10 years, and 31 (89%) and 29 (83%) at 18 years. At 10 years, the EP born boys were given significantly poorer scores by their parents than term-born controls on most CHQ and CBCL scales, but the differences were minor at 18 years; i.e., significant improvements had occurred in several CHQ (self-esteem, general health and parental impact-time) and CBCL (total problem, internalizing and anxious/depressed) scales. For the girls, the differences were smaller at 10 years and remained unchanged by 18 years. Emotional/behavioral difficulties at 10 years similarly predicted poorer improvement on CHQ-scales for both EP and term-born subjects at 18 years. Self-assessment of HRQoL and behavior at 18 years was similar in the EP and term-born groups on most scales.Conclusions. HRQoL and behavior improved towards adulthood for EP born boys, while the girls remained relatively similar, and early emotional and behavioral difficulties predicted poorer development in HRQoL through adolescence. These data indicate that gender and a longitudinal perspective should be considered when addressing health and wellbeing after extremely preterm birth.

Compare respiratory health in children born extremely preterm (EP) or with extremely low birthweight (ELBW) nearly one decade apart, hypothesizing that better perinatal management has led to better outcome.Fifty-seven (93%) of 61 eligible 11-year old children born in Western Norway in 1999-2000 with gestational age (GA)