Expiratory airflow limitation in adults born extremely preterm: A systematic review and meta-analysis.

Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary trauma, thereby posing a lifelong risk to respiratory health. We conducted a systematic review and meta-analysis to investigate adult lung function following EP birth (gestational age <28 weeks); comparing forced expiratory volume in first second (FEV1), forced vital capacity (FVC), and FEV1/FVC to reference values. Subgroup differences were explored based on timing of birth relative to surfactant use (1991) and bronchopulmonary dysplasia (BPD) status. Systematic searches were performed in Medline, EMBASE, Web of Science and Cochrane Central. Quality assessments were carried out using a modified Newcastle-Ottawa Scale for cohort studies. Sixteen studies encompassing 1036 EP-born adults were included, with 14 studies (n = 787) reporting data as %predicted, and 11 (n = 879) as z-score (not mutually exclusive). Overall mean [95 % confidence interval (CI)] %FEV1 was 85.30 (82.51; 88.09), %FVC was 94.33 (91.74; 96.91), and FEV1/FVC was 79.54 (77.71 to 81.38), all three with high heterogeneity. Overall mean (95 %CI) zFEV1 was -1.05 (-1.21; -0.90) and zFVC was. -0.45 (-0.59; -0.31), both with moderate heterogeneity. Subgroup analyses revealed no difference in FEV1 before versus after widespread use of surfactant, but more impairments after neonatal BPD. This meta-analysis revealed significant airflow limitation in EP-born adults, mostly explained by those with neonatal BPD. FEV1 was more reduced than FVC, and FEV1/FVC was at the lower limit of normal. Although at a group level, most adult EP-born individuals do not meet COPD criteria, these findings are concerning.

Health-related quality of life in two birth cohorts of extremely preterm born adults.

AIM: Investigate potential long-term cohort influences on health-related quality of life (HRQoL) in adults born extremely preterm (EP) during the 1980-90s, in view of advancements in neonatal care within that timeframe. METHODS: Two cohorts of EP-born adults (82-85 cohort and 91-92 cohort) enrolling matched term controls, were compared. Participants were assessed at 18 years and again in their mid-twenties using the Child Health Questionnaire Children Form-87 (CHQ-CF87) and the Short Form Health Survey (SF-36). RESULTS: At 18 years, 77 (90%) EP-born and 75 (93%) term controls had data, followed by 67 (78%) EP-born and 66 (82%) term controls in their mid-twenties. At 18 years, there were no differences across the birth decades, and EP-born and term-born reported relatively similar HRQoL scores. In the mid-twenties, birth decade did also not significantly impact HRQoL scores, although the EP-born 82-85 cohort scored numerically poorer than the 91-92 cohort in three domains. Term controls scored similarly across birth decade in all domains. Regarding influence from neonatal factors, postnatal corticosteroids had a negative impact in some domains. CONCLUSION: No significant differences in HRQoL were observed between EP-born adults from the 82-85 cohort versus the 91-92 cohort, although the EP-born 82-85 cohort tended to score poorer in their mid-twenties.

Unravelling the respiratory health path across the lifespan for survivors of preterm birth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease.

Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

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.

Diagnosis of vocal cord dysfunction/inducible laryngeal obstruction: An International Delphi Consensus Study.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathing difficulties in association with excessive supraglottic or glottic laryngeal narrowing. The condition is common and can occur independently; however, it may also be comorbid with other disorders or mimic them. Presentations span multiple specialties and misdiagnosis or delayed diagnosis is commonplace. Group-consensus methods can efficiently generate internationally accepted diagnostic criteria and descriptions to increase clinical recognition, enhance clinical service availability, and catalyze research. OBJECTIVES: We sought to establish consensus-based diagnostic criteria and methods for VCD/ILO. METHODS: We performed a modified 2-round Delphi study between December 7, 2021, and March 14, 2022. The study was registered at ANZCTR (Australian New Zealand Clinical Trials Registry; ACTRN12621001520820p). In round 1, experts provided open-ended statements that were categorized, deduplicated, and amended for clarity. These were presented to experts for agreement ranking in round 2, with consensus defined as ≥70% agreement. RESULTS: Both rounds were completed by 47 international experts. In round 1, 1102 qualitative responses were received. Of the 200 statements presented to experts across 2 rounds, 130 (65%) reached consensus. Results were discussed at 2 international subject-specific conferences in June 2022. Experts agreed on a diagnostic definition for VCD/ILO and endorsed the concept of VCD/ILO phenotypes and clinical descriptions. The panel agreed that laryngoscopy with provocation is the gold standard for diagnosis and that ≥50% laryngeal closure on inspiration or Maat grade ≥2 define abnormal laryngeal closure indicative of VCD/ILO. CONCLUSIONS: This Delphi study reached consensus on multiple aspects of VCD/ILO diagnosis and can inform clinical practice and facilitate research.

Histologic chorioamnionitis in extremely preterm births, microbiological findings and infant outcome.

BACKGROUND: Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract. OBJECTIVES: To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates. METHODS: Prospective observational cohort study recruiting EP singleton pregnancies (gestational age at birth ≤28 weeks) with confirmed HCA. FIR was defined by fetal neutrophils in the chorionic vessels and/or umbilical vessels. Positive culture was defined as growth of potentially pathogenic bacteria in a sample from the cervicovaginal tract prior to birth, or if a cervicovaginal culture was lacking, a culture result from the placenta was used. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between FIR, a positive culture result and adverse outcomes, defined as bronchopulmonary dysplasia (BPD), brain pathology assessed by magnetic resonance imaging, retinopathy of prematurity, necrotizing enterocolitis, early-onset neonatal sepsis, and perinatal death. A composite outcome variable included one or more adverse outcomes. RESULTS: We included 71 cases with HCA, of which 51 (72%) had FIR. Maternal age, rate of clinical chorioamnionitis (CCA), preterm pre-labor rupture of membranes (PPROM), the number of women receiving antenatal steroids and antibiotics, and the rate of positive maternal cultures of potentially pathogenic bacteria were all significantly higher in the HCA with FIR. Neonates in the FIR group had significantly higher levels of blood leukocytes compared to those without. FIR was associated with a longer interval from PPROM to delivery (log-rank test: p = .022). Microbiological sampling had been performed in 63 (89%) cases, of which 60 (95%) were cervicovaginal samples. No associations were found between a positive culture and adverse neonatal outcomes, in contrast to FIR, that was significantly associated to BPD and brain pathology. CONCLUSIONS: In a cohort of EP pregnancies with confirmed HCA, the presence of FIR was associated with advanced maternal age, CCA, PPROM, antenatal steroids and antibiotics, and a positive maternal culture of potentially pathogenic bacteria. However, the presence of FIR, and not a positive culture, was associated with adverse neonatal outcomes.

Are BMI and adipokines associated with asthma, atopy and lung function in young adults previously hospitalized for bronchiolitis?

BACKGROUND: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects. METHODS: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms. RESULTS: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group. CONCLUSION: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism.

Blood eosinophils during bronchiolitis: Associations with atopy, asthma and lung function in young adults.

AIM: To study if blood eosinophils during bronchiolitis were associated with atopy, asthma and lung function in young adults and if these associations differed between respiratory syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis. METHODS: This historical cohort enrolled 225 subjects. Blood eosinophils were measured during bronchiolitis in infancy, and the subjects were invited to a follow-up at 17-20 years of age including questionnaires for asthma and examinations of lung function and atopy. RESULTS: The level of eosinophils was positively associated with subsequent atopy in the unadjusted analysis, but not in the adjusted analysis, and not with asthma. There was a negative association between the level of eosinophils and forced vital capacity (FVC) (-0.11; -0.19, -0.02) and forced expiratory volume in first second (FEV1 ) (-0.12; -0.21, -0.03) (regression coefficient; 95% confidence interval). The non-RSV group had higher levels of eosinophils during bronchiolitis, but there was no interaction between the level of eosinophils and RSV status for any outcome. CONCLUSIONS: The level of eosinophils during bronchiolitis was negatively associated with lung function in young adult age, but we found no associations with atopy or asthma. These associations were not different after RSV bronchiolitis compared to non-RSV bronchiolitis.

Use of inhaled ipratropium bromide to improve exercise-induced laryngeal obstruction cannot be recommended.

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.

Differences in lung function, bronchial hyperresponsiveness and respiratory health between elite athletes competing in different sports.

The aim of this study was to examine lung function, bronchial hyperresponsiveness (BHR) and exercise-induced respiratory symptoms in elite athletes performing different sports. Norwegian national-team athletes (30 swimmers, 32 cross-country skiers, 16 speed-skaters, 11 rowers/paddlers, 17 handball players and 23 soccer players) completed a validated questionnaire, measured exhaled nitric oxide (FENO), spirometry, methacholine provocation (PD20met) and skin prick test. Three cut-off levels defined BHR; i.e. PD20met ≤2 µmol, ≤4 µmol and ≤8 µmol. Mean forced vital capacity (FVC) was highest in swimmers (Mean z-score[95%CI] = 1.16 [0.80, 1.51]), and close to or higher than reference values according to the Global Lung Initiative equation, across all sports. Mean forced expiratory volume in 1 s (FEV1) was higher than reference values in swimmers (0.48 [0.13, 0.84]), and ball game athletes (0.69 [0.41, 0.97]). Mean forced expiratory flow between 25 and 75% of FVC (FEF25-75), and/or FEV1/FVC were lower than reference values in all endurance groups. BHR defined by ≤2 and ≤8 µmol methacholine was observed in respectively 50%-87% of swimmers, 25%-47% of cross-country skiers, 20%-53% of speed-skaters, 18%-36% of rowers/paddlers, and 0%-17% of the ball game athletes. Exercise-induced symptoms were common in all groups, most frequent in cross-country skiers (88%), swimmers (83%) and speed-skaters (81%).HighlightsSwimmers and ball game athletes had higher mean FVC and FEV1 when compared to the reference values predicted by the Global Lung Initiative (GLI) reference equation. Contrasting this, across all sports except ball game athletes, mean FEF25-75 and/or FEV1/FVC were lower than reference values.The prevalence of bronchial hyperresponsiveness (BHR) was high among elite athletes competing in swimming, cross-country skiing, speed skating and rowing/paddling, with swimmers being most affected.The majority of the elite athletes reported exercise-induced respiratory symptoms independent of lung function or BHR.

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.

The association of change in peak oxygen uptake with use of psychotropics in community-dwelling older adults - The Generation 100 study.

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.

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.

A Psychological Investigation of Selection Criteria for Learning Agents (Super Users) and Allocation of Responsibilities in the Implementation of Technological Change.

Purpose: In the introduction of new technologies into organizations, there has been an increasing trend to recruit and make use of the so-called "super users" to help ensure the future use of the technology in question. Little is known about the criteria that should ideally be considered in the selection of these super users, or about the best way to carve up the roles and responsibilities in this process between super users and middle management. In this study, we investigated (1) which criteria should be emphasized in the selection of super users, and (2) how middle management and super users understand and negotiate the responsibilities of their respective roles during implementation of technological change. Methods: We conducted 10 individual semi-structured interviews and used thematic analysis of this data set to identify selection criteria, roles, and responsibilities. Results: We found that the main selection criteria for super users should be: (1) availability and local knowledge, (2) technological skills, (3) pedagogical skills, and (4) proactiveness. The main roles and responsibilities that should be carved up between management and super users can be grouped into two overarching categories, each with several subcategories. Within the Learning culture category, the responsibilities are to (1) facilitate collective learning, (2) engage with criticism, and (3) promote collective sharing; and within the Individual learning category, to (4) facilitate individual learning, (5) provide instrumental support, and (6) provide emotional support. Discussion and Conclusion: Based on the findings, we propose a conceptual model of technological implementation and the construction of a culture of organizational learning, entitled ECo-System Of Learning in Organizations (ECSO-Learn); we additionally show how a learning agent (previously known as a super user) can be recruited to best fit into this model of long-term organizational learning.

Adjustments of non-invasive ventilation and mechanically assisted cough by combining ultrasound imaging of the larynx with transnasal fibre-optic laryngoscopy: a protocol for an experimental study.

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.