Ola Røksund

Continuous Laryngoscopy Exercise Test: A Method for Visualizing Laryngeal Dysfunction during Exercise

Objectives/Hypothesis: To assess the diagnostic feasibility and patient acceptance of a new developed diagnostic test for exercise induced upper airway flow limitation.

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.

Characteristics of asthma and airway hyper‐responsiveness after premature birth

Asthma‐like symptoms and airway hyper‐responsiveness (AHR) are frequently reported in children subsequent to premature birth and bronchopulmonary dysplasia (BPD). There is limited knowledge on the mechanisms underlying these respiratory manifestations. Generally, childhood asthma and AHR is described within a context of inheritance, allergy and eosinophilic airway inflammation, and often in relation to cigarette exposures. We investigated these factors in relation to current asthma and AHR in a population‐based cohort of 81 young people, born with gestational age ≤28 wk or birth weight ≤1000 g, and in a matched term‐born control population. In the pre‐term population, asthma and AHR were additionally studied in relation to neonatal respiratory morbidity. At follow up, more pre‐term than control subjects had asthma. Forced expiratory volume in first second (FEV1) was reduced, AHR was substantially increased, and the level of the urinary leukotriene metabolite E4 (U‐LTE4) was increased in the pre‐term population compared to the term‐born. In control subjects, asthma and AHR was associated with a pattern consistent with inheritance, allergy, airway inflammation, and cigarette exposures. In the pre‐terms, asthma and AHR was either unrelated or less related to these factors. Instead, AHR was strongly related to a neonatal history of BPD and prolonged requirement for oxygen treatment. In conclusion, asthma and AHR subsequent to extremely premature birth differed from typical childhood asthma with respect to important features, and AHR was best explained by neonatal variables. These respiratory manifestations thus seem to represent a separate clinical entity.

Exercise induced dyspnea in the young. Larynx as the bottleneck of the airways.

BACKGROUND Exercise induced asthma may symptomatically be difficult to differentiate from exercise related obstruction in the upper airways, sometimes leading to diagnostic confusion and inappropriate treatment. Larynx accounts for a significant fraction of total airway resistance, but its role as a limiting factor for airflow during exercise has been hampered by lack of diagnostic tools. We aimed to study laryngeal function in exercising humans by transnasal laryngoscopy. METHODS Continuous video recording of the larynx was performed in parallel with continuous film recording of the upper part of the body and recording of breath sounds in subjects running to respiratory distress or exhaustion on a treadmill. RESULTS A successful examination was obtained in 20 asymptomatic volunteers and 151 (91%) of 166 young patients with a history of inspiratory distress or stridor during exercise. At rest, six patients had abnormal laryngeal findings. During exercise, a moderate or severe adduction of laryngeal structures was observed in parallel with increasing inspiratory distress in 113 (75%) patients. In 109 of these, adduction started within supraglottic structures, followed by adduction of the vocal cords in 88. In four patients, laryngeal adduction started in the vocal cords, involving supraglottic structures secondarily in three. CONCLUSION Larynx can safely be studied throughout a maximum intensity exercise treadmill test. A characteristic laryngeal response pattern to exercise was visualised in a large proportion of patients with suspected upper airway obstruction. Laryngoscopy during ongoing symptoms is recommended for proper assessment of these patients.

Left Vocal Cord Paralysis After Extreme Preterm Birth, a New Clinical Scenario in Adults

OBJECTIVE: The goal was to study the incidence and long-term consequences of left vocal cord paralysis (LVCP) after neonatal surgical treatment of patent ductus arteriosus (PDA) in a population-based cohort of adults who were born at gestational ages of ≤28 weeks or with birth weights of ≤1000 g in western Norway. METHODS: Subjects with a history of neonatal PDA surgery were examined with transnasal flexible laryngoscopy, and those with LVCP were examined with continuous laryngoscopy during maximal treadmill exercise (continuous laryngoscopy exercise testing). All subjects underwent lung function testing, ergospirometry, and pulmonary high-resolution computed tomography. Symptoms were recorded with a questionnaire. RESULTS: Forty-four (86%) of 51 eligible preterm infants participated in the study, 13 (26%) had a history of PDA surgery and 7 (54%) had LVCP, with the laryngeal appearances varying slightly. As a group, subjects with LVCP had significant airway obstruction, no decreases in aerobic capacity, and no obvious evidence of longstanding aspiration on high-resolution computed tomography scans. The continuous laryngoscopy exercise tests revealed increasing respiratory symptoms in parallel with increasing anteromedial collapse of the left aryepiglottic folds as the exercise load increased. Hoarseness and voice-related symptoms were the most typical complaints. Symptoms were attributed erroneously to other diseases for at least 2 subjects. CONCLUSIONS: LVCP is not uncommon in young adults exposed to PDA surgery as preterm infants. The condition may be overlooked easily, and symptoms may be confused with those of other diseases. Laryngoscopy should be offered on the basis of liberal indications after PDA ligation.

Better care of immature infants; has it influenced long-term pulmonary outcome?

AIMS To assess whether lung function in late childhood had improved in subjects born extremely prematurely in the early 1990s compared to the early 1980s, and whether neonatal factors in the respective periods had different impact on long-term pulmonary outcome. DESIGN Population-based, controlled cohort study. Lung function was determined in 81 of 86 (94%) eligible subjects born with gestational age < or =28 weeks or birthweight < or =1000 g in Western Norway in 1982-85 (n=46) and 1991-92 (n=35), and in 81 matched control subjects born at term. RESULTS The incidence of bronchopulmonary dysplasia was similar in the two periods. At follow-up, airway obstruction, hyper-responsiveness and pulmonary hyperinflation were similarly increased in both preterm cohorts compared to matched controls. Furthermore, current lung function was similarly related to neonatal respiratory disease in both birth-cohorts: FEV1 was reduced with respectively 18.6% and 18.7% of predicted in preterms dependent on supplemental oxygen at 36 weeks postmenstrual age. Lack of antenatal treatment with corticosteroids and prolonged neonatal oxygen treatment predicted similar significant airway obstruction in the two birth-cohorts. CONCLUSION Preterms born in different eras of neonatology had similar long-term decreases in lung function. Long periods of oxygen supplementation are still required to salvage immature infants, and airway obstruction may still be a common long-term outcome.

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.

Resting energy expenditure and lung disease in cystic fibrosis

Optimal nutritional support is considered to be an integral part in the management of cystic fibrosis (CF). Several factors contribute to increased resting energy expenditure (REE), which itself can lead to energy imbalance and thus contribute to deterioration of the nutritional status. We aimed to assess the impact of lung parenchyma damage on REE and correlated these findings with forced expiratory volume in 1 s (FEV(1)). Twenty patients performed respiratory function testing (FEV(1)), pulmonary high-resolution computed tomography (HRCT) and assessment of REE with open circuit indirect calorimetry. HRCT was scored by using a modified Bhalla method. Mean HRCT score was 8.4 and mean REE value was 108.4% predicted vs. 96.5% predicted of 16 healthy subjects (P<0.01). There was a significant correlation between HRCT score and REE (P<0.01), HRCT score and FEV(1) (P<0.001) and REE and FEV(1) (P<0.05). The correlations demonstrate a close correlation between lung damage and elevated REE in people with CF. Prevention of negative energy balance is an important part in follow-up of patients with CF. Any increase in REE should raise suspicion of progress in lung impairment.

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.