BackgroundMost 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.MethodsWe 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.ResultsAt 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.ConclusionsLaryngoscopy 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.

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.

Background Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at <32 weeks' gestation) or with very low birthweight (<1501 g) is unknown. We aimed to compare maximal expiratory airflow in these individuals during late adolescence and early adulthood with that of control individuals born with normal birthweight (>2499 g) or at term. MethodsWe did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which fewparticipants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV₁, forced vital capacity [FVC], FEV₁/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF 25-75% ]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. Findings Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3·4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV₁ (-0·06 [SD 1·03] vs -0·81 [1·33], mean difference -0·78 [95% CI -0·96 to -0·61], p<0·0001), FVC (-0·15 [0·98] vs -0·38 [1·18], -0·25 [-0·40 to -0·10], p=0·0012), FEV₁/FVC ratio (0·14 [1·10] vs -0·64 [1·35], -0·74 [-0·85 to -0·64], p<0·0001), and FEF 25-75% (-0·04 [1·10] vs -0·95 [1·47], -0·88 [-1·12 to -0·65], p<0·0001). Similar patterns were observed when we compared the proportions of individuals with values below the fifth percentile.Interpretation Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood.

Despite their high-risk start to life and a series of potential shortcomings, subjects born preterm may achieve normal exercise capacity, and their response to physical training seems comparable to peers born at term.

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.

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.

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.

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.