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.

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.

Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight.

BACKGROUND: Lifelong pulmonary consequences of being born extremely preterm or with extremely low birth weight remain unknown. We aimed to describe lung function trajectories from 10 to 35 years of age for individuals born extremely preterm, and address potential cohort effects over a period that encompassed major changes in perinatal care. METHODS: We performed repeated spirometry in three population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g during 1982-85, 1991-92 and 1999-2000, referred to as extremely preterm-born, and in term-born controls matched for age and gender. Examinations were performed at 10, 18, 25 and 35 years. Longitudinal data were analysed using mixed models regression, with the extremely preterm-born stratified by bronchopulmonary dysplasia (BPD). RESULTS: We recruited 148/174 (85%) eligible extremely preterm-born and 138 term-born. Compared with term-born, the extremely preterm-born had lower z-scores for forced expiratory volume in 1 s (FEV1) at most assessments, the main exceptions were in the groups without BPD in the two youngest cohorts. FEV1 trajectories were largely parallel for the extremely preterm- and term-born, also during the period 25-35 years that includes the onset of the age-related decline in lung function. Extremely preterm-born had lower peak lung function than term-born, but z-FEV1 values improved for each consecutive decade of birth (p=0.009). More extremely preterm-than term-born fulfilled the spirometry criteria for chronic obstructive pulmonary disease, 44/148 (30%) vs 7/138 (5%), p<0.001. CONCLUSIONS: Lung function after extremely preterm birth tracked in parallel, but significantly below the trajectories of term-born from 10 to 35 years, including the incipient age-related decline from 25 to 35 years. The deficits versus term-born decreased with each decade of birth from 1980 to 2000.

Development of lung diffusion to adulthood following extremely preterm birth.

BACKGROUND: Gas exchange in extremely preterm (EP) infants must take place in fetal lungs. Childhood lung diffusing capacity of the lung for carbon monoxide (D LCO) is reduced; however, longitudinal development has not been investigated. We describe the growth of D LCO and its subcomponents to adulthood in EP compared with term-born subjects. METHODS: Two area-based cohorts born at gestational age ≤28 weeks or birthweight ≤1000 g in 1982-1985 (n=48) and 1991-1992 (n=35) were examined twice, at ages 18 and 25 years and 10 and 18 years, respectively, and compared with matched term-born controls. Single-breath D LCO was measured at two oxygen pressures, with subcomponents (membrane diffusion (D M) and pulmonary capillary blood volume (V C)) calculated using the Roughton-Forster equation. RESULTS: Age-, sex- and height-standardised transfer coefficients for carbon monoxide (K CO) and D LCO were reduced in EP compared with term-born subjects, and remained so during puberty and early adulthood (p-values for all time-points and both cohorts ≤0.04), whereas alveolar volume (V A) was similar. Development occurred in parallel to term-born controls, with no signs of pubertal catch-up growth nor decline at age 25 years (p-values for lack of parallelism within cohorts 0.99, 0.65, 0.71, 0.94 and 0.44 for z-D LCO, z-V A, z-K CO, D M and V C, respectively). Split by membrane and blood volume components, findings were less clear; however, membrane diffusion seemed most affected. CONCLUSIONS: Pulmonary diffusing capacity was reduced in EP compared with term-born subjects, and development from childhood to adulthood tracked in parallel to term-born subjects, with no signs of catch-up growth nor decline at age 25 years.

Conundrums in the breathless athlete; exercise-induced laryngeal obstruction or asthma?

PURPOSE: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are the two disorders commonly considered when athletes complain of exertional dyspnea. They are highly different but often confused. We aimed to address this diagnostic challenge and its consequences in elite athletes. METHODS: We included all athletes competing at national or international level, referred to our institution for workup for EILO during 2013-2016. We diagnosed EILO from video-recorded laryngoscopy performed during maximal cardiopulmonary treadmill exercise (CLE test). Symptoms and previous diagnostic evaluations were obtained from referral letters and chart reviews. RESULTS: Exercise-induced laryngeal obstruction was diagnosed in 73/101 referred athletes, of whom 70/73 had moderate/severe supraglottic obstruction and 3/73 had primarily glottic obstruction with only minor supraglottic involvement. Of the 73 athletes with EILO, we were able to identify objective tests for asthma in 55 participants, of whom 22 had findings supporting asthma. However, 58/73 had used asthma therapy at some time previously, with current use in 28. Only three reported that asthma medication had improved their exercise-related breathing problems, two of whom with tests confirming asthma. Treatment for EILO improved breathing problems in all but four. CONCLUSIONS: Objective testing verified EILO in most of the referred athletes. EILO coexisting with asthma was common, and large proportions had used asthma medication; however, few reported effect on exercise-related breathing problems. Unexplained persistent exertional dyspnea must not lead to indiscriminate escalation of asthma treatment, but instead incite investigation for EILO, either as a co-morbidity or as a differential diagnosis.

Associations between biological maturity level, match locomotion, and physical capacities in youth male soccer players.

INTRODUCTION: Biological maturity level has shown to affect sport performance in youths. However, most previous studies have used noninvasive methods to estimate maturity level. Thus, the main aim of the present study was to investigate the association between skeletal age (SA) as a measure of biological maturation level, match locomotion, and physical capacity in male youth soccer players. METHOD: Thirty-eight Norwegian players were followed during two consecutive seasons (U14 and U15). Match locomotion was assessed with GPS-tracking in matches. SA, assessed by x-ray, physical capacities (speed, strength and endurance) and anthropometrics were measured in the middle of each season. Analysis of associations between SA, match locomotion, and physical capacities were adjusted for the potential confounding effect of body height and weight. RESULTS: In matches, positive associations were found between SA and maximal speed and running distance in the highest speed zones. Further, SA was associated with 40 m sprint time and countermovement jump (CMJ) height, and with intermittent-endurance capacity after adjusting for body height (U14). Associations between SA and leg strength and power, and between SA and absolute VO2max were not significant after adjusting for body weight. There was no association between SA and total distance covered in matches. CONCLUSION: Biological maturity level influence match locomotion and performance on physical capacity tests. It is important that players, parents and coaches are aware of the advantages more mature players have during puberty, and that less mature players also are given attention, appropriate training and match competition to ensure proper development.

Exercise-induced laryngeal obstruction (EILO) in athletes: a narrative review by a subgroup of the IOC Consensus on 'acute respiratory illness in the athlete'.

Exercise-induced laryngeal obstruction (EILO) is caused by paradoxical inspiratory adduction of laryngeal structures during exercise. EILO is an important cause of upper airway dysfunction in young individuals and athletes, can impair exercise performance and mimic lower airway dysfunction, such as asthma and/or exercise-induced bronchoconstriction. Over the past two decades, there has been considerable progress in the recognition and assessment of EILO in sports medicine. EILO is a highly prevalent cause of unexplained dyspnoea and wheeze in athletes. The preferred diagnostic approach is continuous visualisation of the larynx (via laryngoscopy) during high-intensity exercise. Recent data suggest that EILO consists of different subtypes, possibly caused via different mechanisms. Several therapeutic interventions for EILO are now in widespread use, but to date, no randomised clinical trials have been performed to assess their efficacy or inform robust management strategies. The aim of this review is to provide a state-of-the-art overview of EILO and guidance for clinicians evaluating and treating suspected cases of EILO in athletes. Specifically, this review examines the pathophysiology of EILO, outlines a diagnostic approach and presents current therapeutic algorithms. The key unmet needs and future priorities for research in this area are also covered.

International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 2: non-infective acute respiratory illness.

Acute respiratory illness (ARill) is common and threatens the health of athletes. ARill in athletes forms a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to non-infective ARill in athletes. The International Olympic Committee (IOC) Medical and Scientific Committee appointed an international consensus group to review ARill in athletes. Key areas of ARill in athletes were originally identified and six subgroups of the IOC Consensus group established to review the following aspects: (1) epidemiology/risk factors for ARill, (2) infective ARill, (3) non-infective ARill, (4) acute asthma/exercise-induced bronchoconstriction and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport (RTS) and (6) acute nasal/laryngeal obstruction presenting as ARill. Following several reviews conducted by subgroups, the sections of the consensus documents were allocated to 'core' members for drafting and internal review. An advanced draft of the consensus document was discussed during a meeting of the main consensus core group, and final edits were completed prior to submission of the manuscript. This document (part 2) of this consensus focuses on respiratory conditions causing non-infective ARill in athletes. These include non-inflammatory obstructive nasal, laryngeal, tracheal or bronchial conditions or non-infective inflammatory conditions of the respiratory epithelium that affect the upper and/or lower airways, frequently as a continuum. The following aspects of more common as well as lesser-known non-infective ARill in athletes are reviewed: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations and risks of illness during exercise, effects of illness on exercise/sports performance and RTS guidelines.

International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 1: acute respiratory infections.

Acute illnesses affecting the respiratory tract are common and form a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. Acute respiratory illness (ARill) can broadly be classified as non-infective ARill and acute respiratory infections (ARinf). The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to ARinf in athletes. The International Olympic Committee (IOC) Medical and Scientific Commission appointed an international consensus group to review ARill (non-infective ARill and ARinf) in athletes. Six subgroups of the IOC Consensus group were initially established to review the following key areas of ARill in athletes: (1) epidemiology/risk factors for ARill, (2) ARinf, (3) non-infective ARill including ARill due to environmental exposure, (4) acute asthma and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport and (6) acute nasal/vocal cord dysfunction presenting as ARill. Several systematic and narrative reviews were conducted by IOC consensus subgroups, and these then formed the basis of sections in the consensus documents. Drafting and internal review of sections were allocated to 'core' members of the consensus group, and an advanced draft of the consensus document was discussed during a meeting of the main consensus core group in Lausanne, Switzerland on 11 to 12 October 2021. Final edits were completed after the meeting. This consensus document (part 1) focusses on ARinf, which accounts for the majority of ARill in athletes. The first section of this consensus proposes a set of definitions and classifications of ARinf in athletes to standardise future data collection and reporting. The remainder of the consensus paper examines a wide range of clinical considerations related to ARinf in athletes: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations, risks of infection during exercise, effects of infection on exercise/sports performance and return-to-sport guidelines.

Clinical responses following inspiratory muscle training in exercise-induced laryngeal obstruction.

PURPOSE: Exercise-induced laryngeal obstruction (EILO) is relatively common in young people. Treatment rests on poor evidence; however, inspiratory muscle training (IMT) has been proposed a promising strategy. We aimed to assess laryngeal outcomes shortly after IMT, and to compare self-reported symptoms with a control group 4-6 years later. METHODS: Two groups were retrospectively identified from the EILO-register at Haukeland University Hospital, Norway; one group had received only information and breathing advice (IBA), and another additionally IMT (IBA + IMT). At diagnosis, all participants performed continuous laryngoscopy during exercise (CLE), with findings split by glottic and supraglottic scores, and completed a questionnaire mapping exercise-related symptoms. After 2-4 weeks, the IBA + IMT-group was re-evaluated with CLE-test. After 4-6 years, both groups were re-assessed with a questionnaire. RESULTS: We identified 116 eligible patients from the EILO-register. Response rates after 4-6 years were 23/58 (40%) and 32/58 (55%) in the IBA and IBA + IMT-group, respectively. At diagnosis, both groups rated symptoms similarly, but laryngeal scores were higher in the IBA + IMT-group (P = 0.003). After 2-4 weeks, 23/32 in the IBA + IMT-group reported symptom improvements, associated with a decrease of mainly glottic scores (1.7-0.3; P < 0.001), contrasting unchanged scores in the 9/32 without symptom improvements. After 4-6 years, exercise-related symptoms and activity levels had decreased to similar levels in both groups, with no added benefit from IMT; however, full symptom resolution was reported by only 8/55 participants. CONCLUSION: Self-reported EILO symptoms had improved after 4-6 years, irrespective of initial treatment. Full symptom resolution was rare, suggesting individual follow-up should be offered.

Bronchial hyper-responsiveness in preterm-born subjects: A systematic review and meta-analysis.

BACKGROUND: Preterm-born survivors have increased respiratory symptoms and decreased lung function, but the nature of bronchial hyper-responsiveness (BHR) is unclear. We conducted a systematic review and meta-analysis for BHR in preterm-born survivors including those with and without chronic lung disease in infancy (CLD) comparing results to term-born subjects. METHODS: We searched eight databases up to December 2016. Included articles compared BHR in preterm-born and term-born subjects. Studies reporting BHR as decreases in forced expiratory volume in 1 second (FEV1 ) after provocation stimuli were included. The analysis used Review Manager V5.3. RESULTS: From 10 638 titles, 265 full articles were screened, and 28 included in a descriptive analysis. Eighteen articles were included in a meta-analysis as they reported the proportion of subjects who had BHR. Pooled odds ratio (OR) estimates (95% confidence interval) for BHR comparing the preterm and term-born groups was 1.88 (1.32, 2.66). The majority of the studies reported BHR after a methacholine challenge or an exercise test. Odds ratio was 1.89 (1.12, 3.19) after methacholine challenge and 2.59 (1.50, 4.50) after an exercise test. Nine of fifteen articles reporting BHR in CLD subjects were included in a meta-analysis. Differences for BHR including for methacholine (OR 4.35; 2.36, 8.03) and exercise (OR 5.13; 1.82, 14.47) were greater in the CLD group compared to the term group. CONCLUSIONS: Preterm-born subjects especially those who had CLD had increased rates of BHR to direct (methacholine) and indirect (exercise) stimuli compared to term-born subjects suggesting subgroups might benefit from anti-inflammatory or bronchodilator therapies.

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.

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.

Exercise inducible laryngeal obstruction: diagnostics and management.

Obstruction of the central airways is an important cause of exercise-induced inspiratory symptoms (EIIS) in young and otherwise healthy individuals. This is a large, heterogeneous and vastly understudied group of patients. The symptoms are too often confused with those of asthma. Laryngoscopy performed as symptoms evolve during increasing exercise is pivotal, since the larynx plays an important role in symptomatology for the majority. Abnormalities vary between patients, and laryngoscopic findings are important for correct treatment and handling. The simplistic view that all EIIS is due to vocal cord dysfunction [VCD] still hampers science and patient management. Causal mechanisms are poorly understood. Most treatment options are based on weak evidence, but most patients seem to benefit from individualised information and guidance. The place of surgery has not been settled, but supraglottoplasty may cure well-defined severe cases. A systematic clinical approach, more and better research and randomised controlled treatment trials are of utmost importance in this field of respiratory medicine.

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.