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.

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.

Breathing patterns in people with exercise-induced laryngeal obstruction.

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.

Diagnosis and management of nasal obstruction in the athlete. A narrative review by subgroup B of the IOC Consensus Group on "Acute Respiratory Illness in the Athlete".

Protection of the health of the athlete is required for high level sporting performance. Acute respiratory illness is the leading cause of illness and can compromise training and competition in athletes. To date the focus on respiratory health in athletes has largely been on acute upper respiratory infections and asthma/exercise induced bronchoconstriction (EIB), while nasal conditions have received less attention. The nose has several important physiological functions for the athlete. Nasal conditions causing obstruction to airflow can compromise respiratory health in the athlete, negatively affect quality of life and sleep, cause mouth breathing and ultimately leading to inadequate recovery and reduced exercise performance. Nasal obstruction can be broadly classified as structural (static or dynamic) or mucosal. Mucosal inflammation in the nose (rhinitis) is the most frequent cause of nasal obstruction and is reported to be higher in athletes (21-74%) than in the general population (20-25%). This narrative review provides the sport and exercise medicine physician with a clinical approach to the diagnosis and management of common nasal conditions that can cause nasal obstruction, ultimately leading to improved athlete health and better sports performance.

Left Vocal Cord Paralysis, Lung Function and Exercise Capacity in Young Adults Born Extremely Preterm With a History of Neonatal Patent Ductus Arteriosus Surgery-A National Cohort Study.

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 (<28 weeks' gestation or birth weight <1,000 g) in Norway during 1999-2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function. Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was -1.8 (-2.3, -1.2), -0.7 (-1.1, -0.3) and -0.3 (-0.5, -0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively. Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.

Severe Exercise-Induced Laryngeal Obstruction Treated With Supraglottoplasty.

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.

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 as well as 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.

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.

Ventilatory Efficiency in Children and Adolescents Born Extremely Preterm.

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 ([Formula: see text]E) and carbon dioxide output ([Formula: see text]CO2) was described by a linear model, and the relationship between tidal volume (VT) and [Formula: see text]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 [Formula: see text]E-[Formula: see text]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 [Formula: see text]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.

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

AIM: 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. METHODS: This Norwegian population-based controlled cohort study focused on all infants (n = 35) born at a gestational age of ≤ 28 weeks or with a birthweight of ≤ 1000 grams in 1991-1992, together with matched term-born controls. Participants underwent spirometry and a maximal cardiopulmonary treadmill exercise test at 10 and 18 years. RESULTS: At 18 years of age, mean (95% confidence interval) peak oxygen consumption (peak VO2 ) was 42.3 (39.2-45.4) vs 45.3 (41.3-49.3) mL/kg/min in the preterm- and term-born groups, while the completed treadmill distance was 915 (837-992) vs 1017 (912-1122) metres. Peak VO2 was unrelated to neonatal factors and current lung function. Changes between 10 and 18 were similar in the two groups, and positive associations between exercise habits and peak VO2 developed during the period. CONCLUSION: Exercise capacity was modestly reduced in adolescents born extremely preterm, but the values were considered normal in most participants. Changes during puberty were similar to those observed for term controls, and the findings suggest similar trainability.

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.

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.