From bedside to bench - In vivo and in vitro evaluation of mechanically assisted cough treatment in a patient with bulbar Amyotrophic Lateral Sclerosis.

When the ability to cough is impaired, secretion clearance may be assisted and augmented by Mechanical Insufflation-Exsufflation (MI-E) treatment. In patients with Amyotrophic Lateral Sclerosis, the efficacy of MI-E may be hampered by counterproductive upper airway responses. Careful adjustment of MI-E settings can be beneficial. During the disease progression, a 41-year-old woman with bulbar Amyotrophic Lateral Sclerosis experienced that treatment with MI-E was exhausting and inefficient. Despite adjustments of settings, all treatment led to retching. A change of MI-E device led to more effective treatment. A bench test revealed variations in flow and pressure waveforms in the two devices. When MI-E treatment fails, differences in equipment delivery need to be considered in addition to the adjustment of MI-E settings.

The severity of sleep hypoventilation in stable chronic obstructive pulmonary disease.

PURPOSE: An increase in PaCO2 is the element that defines sleep hypoventilation (SH). We queried if patients with SH, and those with PaCO2 increases during sleep for shorter time periods than SH (shamSH) differed from the patients without SH (noSH) in other ways. METHODS: This was a retrospective re-analysis of data from 100 stable inpatients with COPD with and without chronic hypercapnic respiratory failure. COPD was defined by criteria of the Global initiative for Chronic Obstructive Lung Disease (GOLD). For this study, SH was defined by an increase in PaCO2 ≥ 1.33 kPa to a value exceeding 6.7 kPa for ≥ 10 min (≥ 20 epochs of 30 s). Patients fulfilling the increase in PaCO2 for less than 10 min (1-19 epochs) were designated shamSH. All patients had daytime arterial blood gases, lung function tests, and polysomnography (PSG) with transcutaneous CO2 (PtcCO2). RESULTS: Of 100 patients, 25 had PtcCO2 increase ≥ 1.33 kPa. One never exceeded 6.7 kPa, 15 had SH, and 9 shamSH. SH and shamSH patients had extra CO2 load (= PtcCO2*time) both during and between the SH periods compared to the noSH group, the SH group more than the shamSH group. CONCLUSION: Using CO2 load as a measure of severity of sleep hypoventilation, SH patients have worse hypoventilation than the shamSH. Both shamSH and SH groups have extra CO2 load during and between SH periods, indicating that the SH/shamSH patients may represent a separate group of true hypoventilators during sleep.

Optimizing expiratory flows during mechanical cough in a pediatric neuromuscular lung model.

Mechanical insufflation-exsufflation (MI-E) is recommended for subjects of all ages with neuromuscular disorders (NMDs) and weak cough. There is a lack of knowledge on the optimal treatment settings for young children. This study aims to determine the MI-E settings providing high expiratory airflow while using safe inspiratory volumes, and to identify possible limits where the benefit of incrementing the MI-E settings to achieve a higher expiratory airflow, decreased. Using an MI-E device and a lung model imitating a 1-year-old child with NMD, we explored the impact of 120 combinations of MI-E pressure and time settings on maximal expiratory airflow and inspiratory volume. High expiratory airflows were achieved with several pressure and time combinations where the exsufflation pressure, followed by insufflation pressure and time, had the greatest impact. The benefit of incrementing the settings to increase the expiratory airflow leveled off for the insufflation pressure and time, but not for the exsufflation pressure. Given exsufflation pressure of -40 or -50 cmH2 O and insufflation time longer than 1 second, a plateau in the expiratory airflow curve was present at insufflation pressures from 25 cmH2 O, whereas a plateau in the inspired volume curve occurred at insufflation pressures from 35 cmH2 O. The present neuromuscular pediatric lung model study showed that expiratory pressure impacts expiratory airflow more than inspiratory pressure and time. An inspiratory and expiratory pressure set between 20 to 30 and -40 cmH2 O, respectively, and an inspiratory time longer than 1 second may be considered as a basis when titrating MI-E settings in young children with NMD. The findings must be confirmed in clinical trials.

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.

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.

Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease.

PURPOSE: More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD. METHODS: Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50% of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2). RESULTS: Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19%) to 13 subjects (42%) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of -8.5 (7.8) (N = 11, P = 0.016). CONCLUSIONS: In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.

Alcohol at bedtime induces minor changes in sleep stages and blood gases in stable chronic obstructive pulmonary disease.

PURPOSE/BACKGROUND: The purpose of this study is to explore the effect of a moderate dose of alcohol on sleep architecture and respiration in chronic obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and hypoxic ventilatory drives in awake, normal individuals and reduces the amount of rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD subjects. METHODS: Prospectively designed, open-label interventional study in a pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients, median forced expiratory volume first second (FEV1) 40.5 % of predicted, median age 65 years, investigated by polysomnography including transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2) in randomized order of either control sleep or intervention with 0.5 g of ethanol/kilogram bodyweight, taken orally immediately before lights off. RESULTS: Alcohol induced a mean increase (95 % confidence interval, [CI]) in the mean ΔPtcCO2 of 0.10 kPa (0.002-0.206, P = 0.047) and a mean decrease (CI) in the REM-sleep percentage of total sleep time (REM % of TST) of 3.1 % (0.2-6.0), (P = 0.020). Six subjects with apnea/hypopnea index (AHI) ≥15 had fewer apneas/hypopneas during alcohol versus control sleep (mean reduction of AHI 11 (1-20), P = 0.046). Alcohol-sleep changes in SpO2, but not in ΔPtcCO2, correlated with daytime arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2). CONCLUSION: Occasional use of a moderate, bedtime dose of alcohol has only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution is appropriate as this study is small and higher doses of alcohol may result in major respiratory depressive and additional negative health effects.

Sleep hypoventilation and daytime hypercapnia in stable chronic obstructive pulmonary disease.

PURPOSE: To explore the associations between sleep hypoventilation (SH) and daytime arterial pressures of carbon dioxide (PaCO2), sleep stages, and sleep apneas/hypopneas (AHI) in subjects with chronic obstructive pulmonary disease (COPD). SH has previously been found in COPD-subjects with chronic hypercapnic respiratory failure (CHRF) using supplementary oxygen (LTOT), and has been proposed as a possible predictor for CHRF. PATIENTS AND METHODS: A prospectively designed observational study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients with a mean forced expiratory volume in 1 second (FEV1) of 1.1 L (42% of predicted) and a mean age of 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2). RESULTS: SH as defined by the American Academy of Sleep Medicine (AASM) was found in 15 of the subjects, seven of whom used LTOT. However, six had SH despite being normocapnic during the daytime (only one on LTOT). Subjects with SH had a greater ΔPtcCO2 increase from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep stages compared to non-SH subjects (mean [standard deviation] between-groups difference =0.23(0.20) kPa, P<0.0005). Subjects with apnea/hypopnea index ≥15 (overlap, N=27) did not differ from those with COPD alone (AHI <5, N=25) in sleep ΔPtcCO2 or daytime PaCO2. A regression model with the variables FEV1, LTOT, and sleep maximum ΔPtcCO2 explained 56% of the variance in daytime PaCO2 (F(3, 94) =40.37, P<0.001). CONCLUSION: In stable COPD, SH as defined by the AASM was found both in normocapnic, non-LTOT subjects and in hypercapnic, LTOT-using subjects. Between-sleep-stage increase in ΔPtcCO2 was higher in subjects with SH. Overlap subjects did not differ from simple COPD subjects in sleep ΔPtcCO2 or daytime PaCO2.

Laryngeal response patterns to mechanical insufflation-exsufflation in healthy subjects.

OBJECTIVE: Mechanical insufflation-exsufflation (MI-E) is used to assist cough in patients with neuromuscular diseases. Clinically, application may be challenging in some patient groups, possibly related to laryngeal dysfunction. Before launching a study in patients, the authors investigated laryngeal responses to MI-E in healthy individuals. DESIGN: Twenty healthy volunteers, aged 21-29 yrs, were studied with video-recorded flexible transnasal fiber-optic laryngoscopy while performing MI-E using the Cough Assist (Respironics, United States) according to a standardized protocol applying pressures of ±20 to ±50 cm H2O. RESULTS: An initial abduction of the vocal folds was observed in all subjects, both during the insufflation and exsufflation phases. Nineteen of the 20 subjects adequately coordinated glottic closure when instructed to cough. When instructed simply to exhale during exsufflation, the glottis stayed open in a majority. Subsequent to an initial abduction during exsufflation and cough, various obstructive laryngeal movements were observed in some subjects, such as narrowing of the vocal folds, retroflexion of the epiglottis, hypopharyngeal constriction, and backward movement of the base of the tongue. CONCLUSIONS: The larynx can be studied with transnasal laryngoscopy during MI-E in healthy individuals. Laryngeal responses to MI-E vary, and laryngoscopy may offer valuable clinical information when applying MI-E in patients with bulbar muscle weakness.

Respiratory complications associated with spinal cord injury.

BACKGROUND: Respiratory complications are the most common cause of acute and long-term morbidity and mortality in patients with spinal cord injury. MATERIAL AND METHODS: The article is based on a non-systematic search in PubMed and the authors' clinical experience in treatment and follow-up of respiratory complications in patients with spinal cord injury. RESULTS: The extent of respiratory complications is dependent on the level of spinal cord injury and the degree of motor completeness. In acute spinal cord injury, 80 % of patients may suffer from respiratory complications. Long-term follow-up indicates that respiratory complications are the most common cause of death in these patients. The most common respiratory complications are atelectasis, pneumonia and respiratory failure. Prevention of respiratory complications must be initiated immediately, independent of the level of spinal cord injury. The question of mechanical ventilation in the acute setting, and also during long-term follow-up must be addressed, along with aggressive secretion management. Patients with spinal cord injury have a high prevalence of sleep apnea that may influence their quality of life and rehabilitation. INTERPRETATION: Respiratory complications are common in patients with spinal cord injury. These patients need a multidisciplinary approach. All disciplines involved must obtain knowledge of respiratory complications in the acute phase and in the longer term, to ensure patients are referred for necessary pulmonary review and follow-up.