Maria Vollsæter

Lung function after preterm birth: development from mid-childhood to adulthood

Background As a result of advances in perinatal care, more small preterm infants survive. There are concerns that preterm birth and its treatments may harm pulmonary development and thereby lead to chronic airway obstruction in adulthood. Objective To assess the development of spirometric lung function variables from mid-childhood to adulthood after extreme preterm birth. Methods Two population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g performed lung function tests at 10 and 18 and at 18 and 25 years of age, respectively, together with matched term-born controls. The results are presented as z scores, normalised for age, sex and height. Longitudinal development was compared for groups born at term and preterm, split by a history of absence (n=20), mild (n=38) or moderate/severe (n=25) neonatal bronchopulmonary dysplasia (BPD). Results The preterm-born cohorts, particularly those with neonatal BPD, had significantly lower forced expiratory volume in 1 s and mid-expiratory flow than those born at term at all assessments (z scores in the range −0.40 to −1.84). Within each of the subgroups the mean z scores obtained over the study period were largely similar, coefficients of determination ranging from 0.64 to 0.82. The pattern of development for the BPD subgroups did not differ from each other or from the groups born at term (tests of interaction). Conclusions Airway obstruction was present from mid-childhood to adulthood after extreme preterm birth, most evident after neonatal BPD. Lung function indices were tracking similarly in the preterm and term-born groups.

Exercise Capacity after Extremely Preterm Birth. Development from Adolescence to Adulthood

RATIONALE Extremely preterm (EP) birth is associated with a series of adverse health outcomes, some of which may be alleviated by improved physical fitness. However, EP-born subjects are reportedly less physically active than term-born peers. Exercise capacity is poorly described in this group, and longitudinal data are needed. OBJECTIVES To compare exercise capacity of adults born EP and at term, and to address developmental patterns from adolescence to adulthood. METHODS An area-based cohort of adults, born in 1982-1985 at gestational age 28 weeks or earlier, or with birth weight of 1,000 g or less, originally examined at 18 years of age, were re-examined at 25 years of age together with individually matched term-born control subjects, using an identical maximal cardiopulmonary treadmill exercise test and validated questionnaires. MEASUREMENTS AND MAIN RESULTS A total of 34 (76%) eligible preterm and 33 (85%) term control subjects successfully completed the exercise test at age 25 years. In the two groups, average (95% confidence interval) peak oxygen consumption was 40.7 (37.9-43.5) and 44.2 (41.0-47.4) ml ⋅ kg(-1)⋅min(-1), respectively, whereas the distance completed on the treadmill was 910 (827-993) m and 1,020 (927-1,113) m. Peak oxygen consumption was unrelated to neonatal factors and current FEV1, but was positively associated with leisure-time physical activity and negatively associated with age at examination. Values obtained at age 18 and 25 years were strongly correlated and within normal range at both examinations. CONCLUSIONS Exercise capacity was modestly reduced in EP-born adults; however, values were within a normal range, positively associated with self-reported physical activity and unrelated to neonatal factors and current airway obstruction.

Adult respiratory outcomes of extreme preterm birth. A regional cohort study.

RATIONALE Lifetime respiratory function after extremely preterm birth (gestational age≤28 wk or birth weight≤1,000 g) is unknown. OBJECTIVES To compare changes from 18-25 years of age in respiratory health, lung function, and airway responsiveness in young adults born extremely prematurely to that of term-born control subjects. METHODS Comprehensive lung function investigations and interviews were conducted in a population-based sample of 25-year-old subjects born extremely prematurely in western Norway in 1982-1985, and in matched term-born control subjects. Comparison was made to similar data collected at 18 years of age. MEASUREMENTS AND MAIN RESULTS At 25 years of age, 46/51 (90%) eligible subjects born extremely prematurely and 39/46 (85%) control subjects participated. z-Scores for FEV1, forced expiratory flow at 25-75% of vital capacity, and FEV1/FVC were significantly reduced in subjects born extremely prematurely by 1.02, 1.26, and 0.88, respectively, and airway resistance (kPa/L/s) was increased (0.23 versus 0.18). Residual volume to total lung capacity increased with severity of neonatal bronchopulmonary dysplasia. Responsiveness to methacholine (dose-response slope; 3.16 versus 0.85) and bronchial lability index (7.5 versus 4.8%) were increased in subjects born extremely prematurely. Lung function changes from 18 to 25 years and respiratory symptoms were similar in the prematurely born and term-born groups. CONCLUSIONS Lung function in early adult life was in the normal range in the majority of subjects born extremely prematurely, but methacholine responsiveness was more pronounced than in term-born young adults, suggesting a need for ongoing pulmonary monitoring in this population.

Children born preterm at the turn of the millennium had better lung function than children born similarly preterm in the early 1990s.

Objective 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. Design Fifty-seven (93%) of 61 eligible 11-year old children born in Western Norway in 1999–2000 with gestational age (GA) <28 weeks or birthweight <1000 gram (EP1999–2000) and matched term-controls were assessed with comprehensive lung function tests and standardized questionnaires. Outcome was compared with data obtained at 10 years of age from all (n = 35) subjects born at GA <29 weeks or birthweight <1001 gram within a part of the same region in 1991–92 (EP1991–1992) and their matched term-controls. Results EP1999–2000 had significantly reduced forced expiratory flow in 1 second (FEV1), FEV1 to forced vital capacity (FEV1/FVC) and forced expiratory flow between 25–75% of FVC (FEF25–75), with z-scores respectively -0.34, -0.50 and -0.61 below those of the term-control group, and more bronchial hyperresponsiveness to methacholine (dose-response-slope 13.2 vs. 3.5; p<0.001), whereas other outcomes did not differ. Low birthweight z-scores, but not neonatal bronchopulmonary dysplasia (BPD) or low GA, predicted poor outcome. For children with neonatal BPD, important lung-function variables were better in EP1999–2000 compared to EP1991–1992. In regression models, improvements were related to more use of antenatal corticosteroids and surfactant treatment in the EP1999–2000. Conclusions Small airway obstruction and bronchial hyperresponsiveness were still present in children born preterm in 1999–2000, but outcome was better than for children born similarly preterm in 1991–92, particularly after neonatal BPD. The findings suggest that better neonatal management not only improves survival, but also long-term pulmonary outcome.

Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis

Background Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation–exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment. Methods We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched volunteers. We used video-recorded flexible transnasal fibre-optic laryngoscopy during MI-E undertaken according to a standardised protocol, applying pressures of ±20 to ±50 cm H2O. Laryngeal movements were assessed from video files. ALS type and characteristics of upper and lower motor neuron symptoms were determined. Results At the supraglottic level, all patients with ALS and bulbar symptoms (n=14) adducted their laryngeal structures during insufflation. At the glottic level, initial abduction followed by subsequent adduction was observed in all patients with ALS during insufflation and exsufflation. Hypopharyngeal constriction during exsufflation was observed in all subjects, most prominently in patients with ALS and bulbar symptoms. Healthy subjects and patients with ALS and no bulbar symptoms (n=6) coordinated their cough well during MI-E. Conclusions Laryngoscopy during ongoing MI-E in patients with ALS and bulbar symptoms revealed laryngeal adduction especially during insufflation but also during exsufflation, thereby severely compromising the size of the laryngeal inlet in some patients. Individually customised settings can prevent this and thereby improve and extend the use of non-invasive MI-E.

Adolescents who were born extremely preterm demonstrate modest decreases in exercise capacity.

We aimed to investigate exercise capacity in adolescents who were born extremely preterm and to study changes through puberty and associations with neonatal data, exercise habits and lung function.

Bronchial hyper-responsiveness after preterm birth

Being born preterm often adversely affects later lung function. Airway obstruction and bronchial hyperresponsiveness (BHR) are common findings. Respiratory symptoms in asthma and in lung disease after preterm birth might appear similar, but clinical experience and studies indicate that symptoms secondary to preterm birth reflect a separate disease entity. BHR is a defining feature of asthma, but can also be found in other lung disorders and in subjects without respiratory symptoms. We review different methods to assess BHR, and findings reported from studies that have investigated BHR after preterm birth. The area appeared understudied with relatively few and heterogeneous articles identified, and lack of a pervasive understanding. BHR seemed related to low gestational age at delivery and a neonatal history of bronchopulmonary dysplasia. No studies reported associations between BHR after preterm birth and the markers of eosinophilic inflammatory airway responses typically found in asthma. This should be borne in mind when treating preterm born individuals with BHR and airway symptoms.

Increased Bronchial Hyperresponsiveness and Higher Asymmetric Dimethylarginine Levels after Fetal Growth Restriction

&NA; Bronchial hyperresponsiveness (BHR), a feature of asthma, is observed in preterm‐born children and has been linked to intrauterine growth restriction. BHR is mediated via airway smooth muscle tone and is modulated by the autonomic nervous system, nitric oxide, and airway inflammation. Interactions among these factors are insufficiently understood. Methacholine‐induced BHR (Met‐BHR), fractional exhaled NO, and systemic soluble markers of nitric oxide metabolism and inflammation were determined in a population‐based sample of 57 eleven‐year‐old children born extremely preterm (gestational age [GA] < 28 wk) or with extremely low birth weight (<1,000 g), and in a matched normal‐birth weight term‐born control group (n = 54). Bronchopulmonary dysplasia (BPD) was defined as the need for oxygen treatment at a GA of 36 weeks. In preterm‐born children, birth weight below the 10th percentile for GA was associated with increased Met‐BHR and higher plasma levels of asymmetric dimethylarginine (ADMA), with an increased odds ratio for being in the upper tertile of Met‐BHR (11.8; 95% confidence interval, 3.3‐42.4) and of ADMA (5.2; 95% confidence interval, 1.3‐20.3). Met‐BHR was correlated to ADMA level (r = 0.27, P = 0.007). There were no significant differences in Met‐BHR, fractional exhaled NO, or z‐FEV1 according to BPD status. No associations with systemic soluble markers of inflammation were observed for Met‐BHR, birth, or BPD status. Intrauterine growth restriction in preterm‐born children was associated with substantially increased Met‐BHR and higher ADMA levels, suggesting altered nitric oxide regulation. These findings contribute to the understanding of the consequences from an adverse fetal environment; they should also be tested in term‐born children.

Laryngeal Responses to Mechanically Assisted Cough in Progressing Amyotrophic Lateral Sclerosis

BACKGROUND: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses. METHODS: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011–2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy. RESULTS: Follow-up time was median 17 (range 6–59) months. In total, 751 laryngoscopy recordings from 67 individual examinations (median 4 per subject, range 2–11 per subject) were analyzed. Adverse laryngeal events that developed with disease progression during insufflation included adduction of true vocal folds in 8 of 9 spinal-onset subjects and adduction of aryepiglottic folds in all subjects, initially at the highest positive pressure and prior to onset of other bulbar symptoms in spinal-onset subjects. As cough became less expulsive with disease progression, laryngeal adduction occurred at lower insufflation pressures. Retroflex movement of the epiglottis was observed in 7 of 13 subjects regardless of insufflation pressures and independent of bulbar involvements. Backward movement of the tongue base occurred regardless of insufflation pressures in all but 1 subject. During exsufflation, constriction of the hypopharynx was observed in all subjects regardless of the presence of bulbar symptoms, after the adverse events that occurred during insufflation. CONCLUSIONS: Applying high insufflation pressures during mechanically assisted cough in ALS can become counterproductive as the disease progresses; importantly also prior to the onset of bulbar symptoms. The application of positive inspiratory pressures should be tailored to the individual patient, and laryngoscopy during ongoing treatment appears to be a feasible tool.

Mid-childhood outcomes after pre-viable preterm premature rupture of membranes

Objectives:Investigate cardiorespiratory outcomes in children surviving previable preterm premature rupture of membranes (PV-PPROM) before 22 weeks’ gestational age (GA) with minimum 2 weeks latency.STUDY Design:Single institution, follow-up of retrospectively identified children who were born after PV-PPROM during 2000–2004, and individually matched preterm-born controls.Results:Eleven PV-PPROM and matched control children were included at mean age of 10.5 and 10.7 years. Rupture of membranes occurred at mean GA 182 and 276 weeks and birth at 283 and 286 weeks, respectively. Compared to controls, the PV-PPROM group had significantly poorer lung function, findings on echocardiography indicating mild pulmonary hypertension, and lower peak oxygen consumption. Chart reviews suggested more motor difficulties and a tendency towards more problems with learning and attention.Conclusion:The findings highlight a preterm-born sub-group in need of targeted long-term monitoring and possibly interventions regarding future cardiorespiratory and neurodevelopmental function.