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Background: In Duchenne muscular dystrophy (DMD), dysphagia is a common but often overlooked symptom, which may affect quality of life (QoL). Its possible causes are progressive deterioration of muscle groups involved in swallowing function (oropharyngeal, inspiratory muscles) or impairment of autonomic function. Objectives: In adult patients with DMD, we aimed to identify predictors of swallowing-related QoL and to compare swallowing-related QoL at different ages. Methods: Forty-eight patients aged 30.0±6.6 years were enrolled. Questionnaires were administered: the Swallowing Quality of Life questionnaire (SWAL-QOL) for swallowing-related QoL assessment, and the Compass 31 for autonomic symptoms assessment. The Brooke Upper Extremity Scale was used for upper limbs muscular function assessment. Respiratory and muscle function tests were performed, including spirometry, arterial blood gases, polysomnography, maximal inspiratory pressure (MIP), maximal expiratory pressure and sniff nasal inspiratory pressure. Results: An abnormal composite SWAL-QOL score (≤86) was found in 33 patients. Autonomic symptoms were mild, while a severity impairment was shown by the Brooke Upper Extremity Scale. Spirometry and muscle strength tests demonstrated severe alterations, while diurnal and nocturnal blood gases were normal, due to effective use of noninvasive ventilation. Independent predictors of the composite SWAL-QOL score were age, MIP and Compass 31. A MIP < 22 had an accuracy of 92% in predicting altered swallowing-related QoL. The composite SWAL-QOL score was worse in subjects > 30 years old than in younger patients (64.5±19.2 vs 76.6±16.3, p < 0.02), due to worse scores in items pertinent to mental and social functioning; scores in domains pertinent to the physical function were similar in both groups. Conclusions: In adult DMD, swallowing-related QoL, which is altered in most patients, can be predicted by age, inspiratory muscles strength and autonomic dysfunction symptoms. While swallowing function is already altered in young patients, swallowing-related QoL can progressively worsen with advancing age due to psychological and social factors.

BACKGROUND: Comparison of the effects of pressure controlled and volume controlled noninvasive ventilations (NIV) has usually been limited to the degree of improvement in blood gases. We compared sleep quality, abnormal respiratory events, and patient-ventilator asynchronies during administration of pressure controlled continuous mandatory ventilation (PC-CMV) and volume controlled continuous mandatory ventilation (VC-CMV) in subjects with amyotrophic lateral sclerosis naive to NIV after titration aimed at maximally improving nocturnal arterial blood gases. METHODS: A crossover evaluation of PC-CMV and VC-CMV was performed in 27 subjects with amyotrophic lateral sclerosis. After baseline polysomnography, ventilators were set in random order so as to warrant similar and satisfactory oxygen saturation and transcutaneous [Formula: see text] in both NIV modalities during day and night. Soon after titration, polysomnography was repeated during administration of each type of NIV. RESULTS: With respect to the baseline night, non-rapid eye movement 3, and rapid eye movement sleep stages increased, and the arousal index decreased during PC-CMV (P = .005, P = .02, and P = .01, PC-CMV vs VC-CMV, respectively) but not during VC-CMV. The arousal index during NIV was correlated to the peak pressure delivered by the ventilators (ρ = 0.47, P < .001). Few abnormal respiratory events were observed in both NIV modes. Patient-ventilator asynchronies were more frequent during VC-CMV (median [IQR] 20.8 [0.0 – 22.0] vs 31.8 [30.1 – 34.0] no./h, PC-CMV vs VC-CMV; P = .002). Twenty-one subjects declared that they preferred PC-CMV therapy. CONCLUSIONS: In the short term, PC-CMV may be a preferred NIV modality to VC-CMV for patients with amyotrophic lateral sclerosis, even when both NIV modes are similarly effective in the correction of hypoventilation. Evaluation of the effectiveness of NIV should not be limited to the assessment of blood gas correction.

Cardiovascular events commonly cause death in amyotrophic lateral sclerosis (ALS) even in patients treated by noninvasive ventilation (NIV).to evaluate autonomic function with the assessment of heart rate variability (HRV) in ALS patients treated by assist pressure control ventilation (APCV) and assist control ventilation (ACV) during sleep.Consecutive ALS patients underwent one polysomnography during APCV and one during ACV. HRV was analyzed both in the total sleep period (from first stage N1 to last awakening) and in a 5-minute period of stable stage N2. Time domain, frequency domain and nonlinear indexes of HRV were measured.Nineteen patients (age 62.0 ± 8.7, 9F/10 M) were studied. The analysis did not reveal differences in blood gasses between NIV modalities, but a longer expiratory time (3.01±0.6 vs 2.8 ± 0.6 s, respectively APCV vs ACV, p = 0.001) and a lower arousal index (17.5 ± 9.1 vs 23.1 ± 13.9, p = 0.02) during APCV. HRV was indicative of higher vagal activity during APCV, especially in the 5-minute periods. In the total sleep periods, the HRV time domain indexes reflecting parasympathetic activity were positively correlated with the expiratory time and negatively with the inspiratory/expiratory time ratio. Low frequencies were positively, and high frequencies negatively, correlated with inspiratory time. HRV and sleep structure parameters were not correlated, except very low frequencies that were correlated to the arousal index.Respiratory influences on autonomic control can be preserved in ALS. The slower breathing pattern during APCV may help to maintain a higher vagal activity. Through this mechanism, in the long-term APCV could more beneficial to ALS patients than ACV.

The aim of this study was to evaluate quality of life (QoL) and its possible determinants in patients affected by Duchenne muscular dystrophy (DMD) in late stages of their disease, when non-invasive ventilation (NIV) is already established. Forty-eight DMD patients who were treated by NIV were enrolled. QoL was assessed by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. By this questionnaire, different aspects of QoL were assessed on a scale from 0 (best) to 100 (worst). In addition, motor and respiratory function tests were performed. Dysautonomia symptoms, sleep quality, sleepiness, anxiety, and depression were evaluated by validated questionnaires. The global INQoL score was 42.8 ± 19, reflecting a moderately altered QoL. The physical health domain was heavily impaired while the psychosocial domain was only mildly affected. Independence had the highest scores (81.1 ± 21.2), proving to be the most affected item. On multivariate analysis, maximal inspiratory pressure and Pittsburgh Sleep Quality Index, but not daily duration of NIV therapy, predicted global INQoL score. Respiratory impairment and sleep quality were independent predictors of poor QoL in DMD patients under NIV. Sleep quality in DMD is often disregarded, while it should be carefully addressed to ensure a better QoL.

In ALS, a high prevalence of sleep apnea has been reported, both of the obstructive (OSA) and of the central type (CSA), but it is unclear if it is associated with nocturnal hypercapnia (NH) and if it is related to patients’ BMI. The aim of this study was to explore, in patients with ALS, the relationship between sleep apnea and NH, and the role of BMI as a risk factor for sleep apnea. Forty-seven patients with ALS, aged 65.4±10.4 years, admitted to our centre for a pneumological evaluation, underwent nocturnal polysomnography with transcutaneous PCO2 (TcPCO2) monitoring. NH was defined as peak TcPCO2 >49 mmHg. Patients without and with NH were compared for the occurrence of sleep apnea, defined as an apnea/hypopnea index (AHI) ≥5, separately of the central and of the obstructive type. Then, BMI of non-sleep apnea subjects was compared with BMI of OSA and CSA patients, separately in the patients without and with NH. Altogether 24 patients showed NH. Eleven patients without, and 13 patients with NH had sleep apnea (p=0.56). In the former group, 64% subjects had predominant CSA and 36% OSA, while in the latter group of patients the corresponding values were 62% and 38% (p=0.77). BMI differed among OSA (32.4±5.1 kg/m2) non-sleep apnea (26.1±4.0 kg/m2) and CSA patients (22.9±4.8 kg/m2) in the group without NH (p=0.006), but not in the group with NH (p=0.44). The similar prevalence of both OSA and CSA in the subjects without and with NH suggests that having sleep apnea is not a risk factor for nocturnal hypoventilation in ALS. A high BMI is a risk factor for OSA in normocapnic ALS patients, as it is in the general population.

Stiff person syndrome (SPS) is a rare neurologic disorder characterized by progressively worsening rigidity and spasms of the axial and limb muscles. Dyspnea has been recently recognized as a common symptom in SPS,1 and life-threatening respiratory crises have been occasionally reported and suspected to be responsible for sudden death in these patients.2,3 The pathophysiologic mechanisms of these respiratory manifestations remain unclear. Some authors have hypothesized that rigidity and/or spasm of the muscles of the trunk could prevent normal rib cage movements and excursion of the diaphragm.1

In amyotrophic lateral sclerosis (ALS), early recognition of nocturnal hypoventilation (NH) is essential to start noninvasive ventilation (NIV), but nocturnal transcutaneous PCO2 (PtcCO2) is difficult to monitor. Usefulness of respiratory and muscular function test in the prediction of NH has been explored without distinguishing among ALS phenotypes. We evaluated cross-sectional relationships between functional tests and nocturnal PCO2, and the best predictors of NH, separately in patients with spinal and bulbar onset of ALS. Methods: ALS patients candidate to NIV were recruited. Diurnal respiratory and muscular function tests and nocturnal polysomnography with PtcCO2 monitoring were performed. NH was defined as peak PtcCO2 >49 mm Hg. Results: Thirty-six patients with spinal and 11 with bulbar onset ALS were included. Nocturnal oxygen saturation and PtcCO2, and proportion of subjects with NH were similar in each group (spinal: 50%; bulbar: 45.5%). Significant differences between groups were found in forced vital capacity (p = 0.03), maximal inspiratory pressure (p = 0.01) and sniff nasal inspiratory pressure (SNIP) (p = 0.007), but not in diurnal arterial blood gases. In the spinal group, SNIP and Base Excess (BE) independently predicted nocturnal PtcCO2 (R2 0.59, p 2, but it varied little in relationship to PtcCO2 changes. Conclusions: Respiratory and muscle function parameters are differently related to NH in ALS patients with spinal and bulbar presentation. SNIP and BE may be helpful to reveal NH in spinal patients, while in bulbar patients no respiratory or muscle function tests may reliably predict NH.

Objective In stable neuromuscular patients under long-term non-invasive ventilation (NIV), subjective sleep quality may be predicted by chronic hypoventilation, as assessed by base excess (BE), and %N3 sleep stage duration. In this study, we explored how other variables, closely associated with self-reported health complaints, contributed to subjective sleep quality in adult patients with Duchenne muscular dystrophy (DMD). Methods This is a secondary analysis of a quality of life study in 48 adult DMD patients under NIV therapy, with little evidence of residual hypoventilation. Subjective sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI). A PSQI score >5 was considered indicative of poor sleep quality. Several other symptoms were evaluated: sleepiness, by the Epworth Sleepiness Scale (ESS); depression and anxiety, by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D); autonomic symptoms, by the Composite Autonomic Symptom Score 31; pain, by the Numeric Pain Rating Scale (NPRS); and fatigue, by the Fatigue Severity Scale (FSS). Results Mean PSQI was 6.1 ± 2.9. Abnormal scores were found for NPRS in 40, for HADS-A in 10 and for FSS in 24 subjects. The NPRS, HADS-A and FSS scores and the N3 sleep stage, independently predicted PSQI (R2 = 0.47, p Conclusions In adult DMD patients, pain, fatigue and anxiety may have a prominent influence on subjective sleep quality. Improvement of sleep quality may be of utmost importance in DMD, as it may ameliorate quality of life and extend its benefits to cardiovascular morbidity and life expectancy.

Background: In ALS, respiratory disturbances during sleep have an important role in the natural history of the disease. Diurnal and nocturnal blood gases are weakly correlated, but nocturnal respiratory disorders are difficult to predict. Aim: To evaluate if SNIP, an important parameter reflecting respiratory muscle strength, is related to nocturnal respiratory disorders and whether it contributes to predict nocturnal blood gas alterations in addition to daytime blood gas levels in ALS. Methods: Forty patients with ALS, after a daytime respiratory function evaluation, including arterial blood gases and SNIP, underwent a polysomnography with transcutaneous capnography (tcPCO2). The patients were stratified according to a SNIP ≥40 cm H2O (group 1) or Results: Group 1 included 13 patients (SNIP=49.0±7.7 cm H2O) and group 2 the remaining 27 subjects (SNIP=18.2±7.2 cmH2O). AHI did not differ between groups (4.6 [1.9-16.3] vs 4.7 [2.4-29.3], respectively, p= 0.35), but group 2, as compared to group 1, had fewer obstructive events (OAHI: 0.5 [0.0-24.4] vs 0.0 [0.0-1.2], respectively, p=0.02). In group 2, at multiple regression analysis, diurnal BE (β =-0.49, p=0.004) and SNIP (β =0.35, p=0.03) proved significant predictors of mean nocturnal SpO2; while diurnal PaCO2 (β =0.42, p=0.02) and SNIP (β =-0.36, p=0.04) predicted peak PtCO2. Conclusions: In ALS patients with SNIP

Introduction Respiratory failure is the leading cause of death in amyotrophic lateral sclerosis (ALS) [1]. The involvement of respiratory function is a negative predictor of survival, which can be in part overcome by a prompt initiation of non-invasive mechanical ventilation (NIV). Seated forced vital capacity (FVC%) is a widely used measure to monitor respiratory function, and it is often taken as a surrogate outcome measure in clinical trials. However, it may be within a normal range in ALS patients with respiratory dysfunction [2]. Here we report on a case of an ALS patient with a rapidly evolving respiratory insufficiency, despite a rather normal FVC%. Case presentation The patient, a 67-year-old man with non-significant past medical history, was referred to our Neurology Unit with 7-month history of progressive impairment of neck muscles that caused dropped head. Symptom onset was subtle, and it was followed by camptocormia. The neurological examination documented the camptocormic posture with a dropped head, and disclosed a mild tongue atrophy, slight hypophonia, and a mild dysphagia, with a moderate proximal and distal weakness and atrophy of the upper limbs; the lower limbs were clinically unaffected. Reflexes were present but not brisk in the four limbs. A complete diagnostic work-up according to current guidelines, including determination of serum anti-ganglioside antibodies, was performed which allowed the diagnosis of ALS. Spirometry was performed to assess the respiratory function: FVC was 80% of predicted, a value within the normal range. Diaphragm compound muscle action potentials (CMAPs) were not measured. The patient did not complain shortness of breath. Physical examination and X-ray showed no sign of diaphragmatic dysfunction. The revised ALS functional rating scale (ALSFRSR) was 42/48 [3], with a predicted intermediate rate of progression (ΔFS = 0.86). The respiratory subscores of the ALSFRS-R were 12/12. The dropped head was corrected with a collar. He started riluzole, and a 4-month follow-up visit was scheduled. Some 30 days after diagnosis, he became increasingly lethargic over a few days and was admitted to the Emergency Unit. Altered arterial blood gases were found (PaO2 26.4 mmHg, PaCO2 93.0 mmHg, pH 7.32). A CT scan of the lungs did not show radiological evidences of pneumonia or atelectasis. When inquired, relatives reported that the patient had his usual lifestyle, that he did not complain in the past days of significant respiratory problems, and that he did not take medications other than riluzole. The patient was intubated and placed on invasive mechanical ventilation, with a prompt improvement of the blood gases, i.e., PaO2 74.3 mmHg, PaCO2 46.0 mmHg, pH 7.47, and a recovery of full consciousness. The assisted mechanical ventilation was continued. One week later, the tracheal tube was removed and noninvasive ventilation (NIV) was started. In the following days,......................

Background and objective No studies have evaluated the impact of different settings of non-invasive ventilation (NIV) in patients affected by amyotrophic lateral sclerosis (ALS). We explored consequences of positive end-expiratory pressure (PEEP) application on effectiveness of ventilation, sleep architecture and heart rate variability (HRV) in patients with ALS naive to ventilatory treatment. Methods In two consecutive nights, 25 patients received in random order 0 or 4 cm H20 of PEEP during nocturnal NIV administration (Idea Ultra ResMed) with the same level of total positive inspiratory pressure. Polysomnographies were performed to evaluate sleep and NIV quality, as well as HRV. HRV was analyzed on 4-h periods and on 5-min segments of stable NREM sleep. Results We did not observe differences in gas exchanges during NIV with and without PEEP. Conversely, during PEEP application increases in leaks (41.4 ± 29.3% vs 31.0 ± 25.7%, P = 0.0007) and in autotriggerings (4.2 (IQR 1.3–10.0) vs 0.9 (IQR 0.0–3.0) events/h, P

Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc.

The study aims to evaluate the performance of autonomic activations as a tool to assess sleep fragmentation and to recognize hypopneas in patients with amyotrophic lateral sclerosis (ALS) under non-invasive mechanical ventilation and secondarily, to evaluate, in patients with the same disease, the relationship between disruption of autonomic nervous system (ANS) activity and the usefulness of the autonomic activations as surrogates of cortical arousals. Sixteen ALS patients underwent simultaneous polysomnography and portable cardiorespiratory monitoring (PM). On the polysomnography, standard rules were used for scoring arousals and respiratory events. On the PM, autonomic arousals were scored as ≥ 15% heart rate (HR) increase with a ≥ 35% pulse wave amplitude (PWA) reduction, HR increase ≥ 20%, or PWA decrease ≥ 40%. Nocturnal HR variability was analyzed in the ALS patients and in 11 control subjects as an index of ANS activity. Synchronized epoch by epoch analysis of the polysomnography and PM recordings showed that only 31.0 (22.5–58.7)% cortical and 36.1 (20.5–47.2)% autonomic arousals were associated with one another. Among hypopneas scored at polysomnography, 71.7% were associated with a cortical arousal but not with a desaturation. On average, HR variability in ALS showed signs of depressed ANS activity that was particularly evident in the patients where the cortical arousals exceeded the autonomic ones. In ventilated ALS patients, autonomic activations may hardly have a role as surrogates of cortical arousals for assessment of sleep fragmentation and for respiratory scoring. Depression of ANS activity may be related to their poor performance.

Patients with neuromuscular diseases improve their sleep when treated with noninvasive ventilation (NIV), but their sleep architecture during NIV may still be disturbed by side effects of NIV or inadequacy of the ventilator setting. Little is known about subjective sleep quality during NIV. The aims of this study were to evaluate subjective sleep quality of stable neuromuscular patients under long-term NIV by using Pittsburgh questionnaire (PSQI), and to assess its possible determinants.Fifty stable neuromuscular patients under long-term NIV were administered PSQI and underwent polysomnography. Arterial blood gases, forced vital capacity, and respiratory muscular strength were measured.Thirty-three patients had global PSQI ≥ 5 and were classified as bad sleepers. Good and poor sleepers differed in age (P = 0.005), base excess (BE) (P = 0.02), NIV inspiratory pressure (P = 0.04), %N1 (P = 0.0006), and %N3 sleep stage (P = 0.02). Percent N3 duration and Arousal/Awakening Index were correlated with rate of patient-ventilator asynchronies (r = -0.41 and 0.37, respectively, P 0.05) and with NIV inspiratory pressure (r = -0.44 and 0.36, P 0.01 and0.05, respectively). At the final multivariate regression model, only BE and %N3 independently predicted global PSQI (r(2) = 0.326, P 0.001).Subjective sleep quality is often poor in neuromuscular patients under long-term NIV. Amount of slow wave sleep and chronic hypoventilation resulting in increased BE are independent predictors of subjective sleep quality. Since inadequate NIV setting or application can influence sleep structure and alveolar ventilation, great care should be paid to the setting and the correct application of NIV to ensure a better subjective sleep quality.

In-hospital polysomnography (PSG) often is performed to monitor neuromuscular patients under noninvasive ventilation (NIV), but success of home PSG has not been established for that purpose. Reliability of sleep diaries in neuromuscular patients is unknown. The aims of our study were to evaluate feasibility, quality, and acceptability of unattended home PSG, as well as the reliability of sleep diaries in neuromuscular patients on long-term NIV.Fifty-two neuromuscular patients underwent unattended home or hospital PSG during NIV. Patients were questioned about their sleep during the PSG and their attitudes towards the procedure.One home and one hospital PSG were scored as failure or low quality due to prolonged signal loss or sleep duration of3h. Objective and subjective sleep duration and efficiency often showed large differences. Subjective awakenings reflected objective awakenings lasting for4 min in 86.5% patients. Preference for home PSG was expressed by 82% subjects.In neuromuscular patients under NIV unattended home PSG is feasible and preferred, with a low failure rate. The degree of reliability of different parameters of subjective sleep assessment should be considered when used as a complement of nocturnal cardiorespiratory recordings.

A 28-year-old neuromuscular patient chronically treated with nocturnal noninvasive ventilation developed pulmonary lobar atelectasis and daytime hypoxemia. Twenty four-hour 5 L/min oxygen was begun, while mechanical cough assist aids were applied for seven days. In the following three days, treatment with nebulized Dornase alpha (rhDNase) b.i.d. was tested, without any significant improvement. On 11 and 13th days rhDNase was instilled by flexible bronchoscopy. A rapid resolution of the atelectasis was observed with relief of hypoxemia, without significant side effects. On day 16 the patient was discharged without oxygen requirements. In non-intubated neuromuscular patients with atelectasis who do not respond successfully to non-invasive treatments intrabronchial instillation of rhDNase may safely help to improve airway clearance. Resumo: Um doente neuromuscular crónico de 28 anos de idade, tratado com ventilação noturna não invasiva, desenvolveu atelectasia lobar pulmonar e hipoxemia diurna. Foi iniciado suporte de oxigénio durante 24 horas, enquanto uma ajuda mecânica para a tosse era aplicada por 7 dias. Nos 3 dias seguintes o tratamento com Dornase alfa nebulizado (rgDNase) b.i.d. foi testado, sem qualquer melhoria significativa. No 11.° e 13.° dias rhDNase foi introduzido por broncoscopia flexível. Um restabelecimento rápido da atelectasia foi observado com alívio da hipoxemia, sem efeitos secundários significativos. No 16.° dia o doente teve alta sem necessidade de oxigénio. Em doentes neuromusculares não intubados, com atelectasia, que não respondam positivamente a tratamentos não invasivos, a introdução intrabronquial de rhDNase pode com segurança ajudar a melhorar a abertura das vias respiratórias. Keywords: Dornase alpha, Neuromuscular diseases, Atelectasis, Palavras-chave: Dornase alfa, Doenças neuromusculares, Atelectasia

Arousals may occur during sleep spontaneously or following respiratory disorders, and are recognised as cortical and/or autonomic activation. Autonomic nervous system (ANS) activity may differ between Duchenne muscular dystrophy (DMD) and amyotrophic lateral sclerosis (ALS). We analysed nocturnal cardiorespiratory (Somnocheck Micro, Weinmann) and polysomnography (PSG) recordings (SomnoLab2, Weinmann), simultaneously performed in ventilated patients, 16 affected by DMD and 16 by ALS. Our aims were to evaluate relationships between: 1) autonomic arousals (AA), detected as pulse wave amplitude variations, and cortical arousals (CA); 2) respiratory AA and disordered breathing events; 3) occurrence of AA and ANS activity, assessed with the analysis of heart rate (HR) variability. Respiratory events and AA were automatically detected by the cardiorespiratory monitor. CA were visually detected on the PSG. HR variability was analysed on the PSG ECG signal by a commercial software (Kubios HRV). In DMD, AA exceeded CA rate (40.4±10 vs 19.7±5 p

Background LOPD is a metabolic, autosomal recessive disease due to a reduced functionality of protein α-glucosidase (GAA), which leads to an accumulation of glycogen in skeletal muscle tissue and in other organs. 70% of LOPD patients develops progressive respiratory failure (RF) with vital capacity reduction and risk of mechanical ventilation. Recent data suggest the importance of an early LOPD diagnosis. Aims Prevalence of LOPD suspect in patients with RF. Optimizing the diagnostic process encouraging early diagnosis. Methods 12 months real-life study, conducted in 18 Pulmonology Italian Centers, aimed to enroll 500 adult patients with unexplained RF and follow the diagnostic algorithm for suspected LOPD. For each patient, clinicians collected a drop of blood on Dried Blood Spot (DBS) for the measurement of GAA. Muscular disability was assessed with Walton Gardner Medwin Scale (WGMS). Results 38 patients enrolled: characteristics and preliminary data in Figure 1. 68% acceded for respiratory reasons, 32% for other causes. 42% was hospitalized and 24% needed mechanical ventilation. Hyperckemia was reported in 34% of patients. The majority of cases (76%) presented a WGMS between 0 and 5. 1 case resulted positive for LOPD suspect (GAA = 0,48 micromol/L/h). Conclusions PneumoLoped could provide original data to focus the role of pulmonologists in LOPD early diagnosis in patients with unexplained RF.

Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc.

For patients with neuromuscular disorders, a noninvasive approach to the management of bronchial secretions, based on a combination of noninvasive positive pressure ventilation and expiratory muscle aid, may result in a reduced need for endotracheal intubation and/or tracheostomy. In addition, preventive application of assisted coughing techniques after extubation may avert the need for reintubation and shorten the intensive care unit stay.

SummaryBackgroundNoninvasive ventilation (NIV) may improve quality of sleep but patient-ventilator asynchronies (PVA) may affect sleep structure. Possible changes in ventilation quality after hospital discharge are poorly known.ObjectiveTo analyse the impact of different kinds of PVA on sleep disruption in chronically ventilated neuromuscular patients after in-hospital optimization of ventilator setting with nocturnal polygraphy, and to compare home and hospital PVA occurrence.MethodsEighteen patients were included in the study. PVA during hospital polygraphic monitoring and during successive home polysomnography were analysed. The relationships between PVA and air leaks, sleep stages, and arousals or awakenings recorded during polysomnography were investigated.ResultsOverall, PVA had a low rate of occurrence (4.32 events/h, IQR 1.75–6.25), but their number was higher during home polysomnographies than in hospital (p = 0.0039): their increase was correlated to an increase in air leaks with respect to hospital monitorings (p = 0.020). Autotriggerings were the most common asynchronies, followed by ineffective efforts (IE) and prolonged insufflations (PI). All asynchronies occurred more often in NREM than in REM sleep. Autotriggerings and IE were more often associated with arousals than PI (p

Background and objective: Although non-invasive ventilation is widely used for the management of patients with neuromuscular disease, it remains unclear which ventilatory mode is associated with optimal patient–ventilator interaction and provides more effective gas exchange. The effects of volume-guaranteed pressure support (PSV-VTG) as compared with pressure support ventilation (PSV) and assisted pressure controlled ventilation (APCV) on breathing pattern and patient–ventilator synchrony during sleep, blood gases and subjective comfort were evaluated in a group of stable patients with neuromuscular disease. Methods: PSV-VTG, PSV and APCV were applied in random order on three consecutive nights, during which cardio-respiratory monitoring was performed. Arterial blood gases were measured at the end of each ventilatory session. Evaluation of subjective sleep quality, comfort and perception of patient–ventilator synchrony was performed using a 10-item visual analogue questionnaire. Results: Twenty-eight patients were included in the study. The different ventilatory modes showed similar effects on breathing pattern during sleep, arterial blood gases and degree of subjective comfort. Ineffective efforts were only observed during PSV-VTG and were inversely correlated with the variability of leaks (r = −0.61, P = 0.015). A greater number of prolonged inspirations was observed with PSV-VTG and PSV compared with APCV (P = 0.048 and 0.029, respectively). There were no correlations between patient comfort and physiological variables or ventilator setting. Conclusions: PSV-VTG did not outperform older modes of ventilation in terms of efficacy on breathing pattern and blood gases. In addition, application of PSV-VTG was associated with a higher rate of patient–ventilator dyssynchrony.

No studies have evaluated the impact of different settings of non-invasive ventilation (NIV) in patients affected by amyotrophic lateral sclerosis (ALS). We explored consequences of positive end-expiratory pressure (PEEP) application on effectiveness of ventilation, sleep architecture and heart rate variability (HRV) in patients with ALS naïve to ventilatory treatment.In two consecutive nights, 25 patients received in random order 0 or 4 cm H2 0 of PEEP during nocturnal NIV administration (Idea Ultra ResMed) with the same level of total positive inspiratory pressure. Polysomnographies were performed to evaluate sleep and NIV quality, as well as HRV. HRV was analyzed on 4-h periods and on 5-min segments of stable NREM sleep.We did not observe differences in gas exchanges during NIV with and without PEEP. Conversely, during PEEP application increases in leaks (41.4 ± 29.3% vs 31.0 ± 25.7%, P = 0.0007) and in autotriggerings (4.2 (IQR 1.3-10.0) vs 0.9 (IQR 0.0-3.0) events/h, P 0.001, PEEP vs no PEEP, respectively) occurred. Besides, N3 sleep stage duration decreased (2.5% (IQR 0.0-18.0) vs 0.0% (IQR0.0-12.1), P = 0.001) and arousal/awakening index increased (16.9 ± 7.4 vs 13.4 ± 5.0 events/h, P = 0.01). Data on HRV were available in 15 patients. A higher low/high frequency ratio, either in the 4-h (3.8 ± 2.6 vs 2.9 ± 1.7, P = 0.04, PEEP vs no PEEP, respectively) or in the 5-min segments (2.6 ± 1.8 vs 1.45 ± 0.9 P = 0.01) was found during PEEP administration.In ALS patients, PEEP application during NIV was associated with worse NIV and sleep quality and with higher sympathetic activity.

In patients with late-onset Pompe disease, we explored the role of the Cardiopulmonary Exercise Test (CPET) and the Six-Minute Walking Test (6MWT) in the assessment of exercise capacity and in the evaluation of the effects of enzyme replacement therapy (ERT). Eight patients affected by late-onset Pompe disease, followed up at the Centre for Neuromuscular Diseases and treated with ERT, underwent a baseline evaluation with a spirometry, a CPET and a 6MWT. Four of them were restudied after 36 months of treatment. Three patients showed a reduction in exercise capacity as evaluated by peak oxygen uptake (VO 2 ) measured at the CPET and Distance Walked (DW) measured at the 6MWT (median % predicted: 67.1 [range 54.3–99.6] and 67.3 [56.6–82.6], respectively). Cardiac and respiratory limitations revealed by the CPET were correlated to peak VO 2 , but not to the DW. Nevertheless, percent of predicted values of peak VO 2 and DW were strongly correlated (rho = 0.85, p = 0.006), and close to identity. In the longitudinal evaluation forced vital capacity decreased, while peak VO 2 and DW showed a trend to a parallel improvement. We concluded that although only the CPET revealed causes of exercise limitation, which partially differed among patients, CPET and 6MWT showed a similar overall degree of exercise impairment. That held true in the longitudinal assessment during ERT, where both tests demonstrated similar small improvements, occurring despite deterioration in forced vital capacity.

BACKGROUND: Improved technology, as well as professional and parental awareness, enable many ventilator-dependent children to live at home. However, the profile of this growing population, the quality and adequacy of home care, and patients' needs still require thorough assessment. OBJECTIVES: To define the characteristics of Italian children receiving long-term home mechanical ventilation (HMV) in Italy. METHODS: A detailed questionnaire was sent to 302 National Health Service hospitals potentially involved in the care of HVM in children (aged

SummaryRespiratory failure is an unavoidable event in the natural history of some neuromuscular diseases, while appearing very infrequently in others. In some cases, such as Pompe disease, respiratory failure progresses more rapidly than motor impairment, sometimes being the onset event. Home mechanical ventilation improves survival and quality of life of these patients, with a reduction in healthcare costs. Therefore, pulmonologists must improve their skills in order to play a more relevant role in the care of these patients. The aim of this statement is to provide pulmonologists with some simple information in order for them to fulfil their role of primary caregiver, enabling appropriate and rapid diagnosis and treatment.

Although non-invasive ventilation is widely used for the management of patients with neuromuscular disease, it remains unclear which ventilatory mode is associated with optimal patient-ventilator interaction and provides more effective gas exchange. The effects of volume-guaranteed pressure support (PSV-VTG) as compared with pressure support ventilation (PSV) and assisted pressure controlled ventilation (APCV) on breathing pattern and patient-ventilator synchrony during sleep, blood gases and subjective comfort were evaluated in a group of stable patients with neuromuscular disease.PSV-VTG, PSV and APCV were applied in random order on three consecutive nights, during which cardio-respiratory monitoring was performed. Arterial blood gases were measured at the end of each ventilatory session. Evaluation of subjective sleep quality, comfort and perception of patient-ventilator synchrony was performed using a 10-item visual analogue questionnaire.Twenty-eight patients were included in the study. The different ventilatory modes showed similar effects on breathing pattern during sleep, arterial blood gases and degree of subjective comfort. Ineffective efforts were only observed during PSV-VTG and were inversely correlated with the variability of leaks (r=-0.61, P=0.015). A greater number of prolonged inspirations was observed with PSV-VTG and PSV compared with APCV (P=0.048 and 0.029, respectively). There were no correlations between patient comfort and physiological variables or ventilator setting.PSV-VTG did not outperform older modes of ventilation in terms of efficacy on breathing pattern and blood gases. In addition, application of PSV-VTG was associated with a higher rate of patient-ventilator dyssynchrony.

The evidence from several studies indicates that as individuals age, they may display immune dysfunctions, mostly T cell dysfunctions. Recently, a soluble form of the receptor for interleukin-2 (IL-2) (sIL-2R) has been demonstrated in human sera and in vitro stimulated culture supernatants from human T lymphocytes. In the present paper, we report in vitro sIL-2R production from peripheral blood mononuclear cells in elderly subjects. The results show that no difference exists for unstimulated cultures, whereas after mitogen stimulation the elderly subjects showed the lowest values compared with young ones. These findings suggest that sIL-2R may provide a new tool for the study of T lymphocyte dysfunctions in old age.

It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte precursors in both groups so that the difference between the two groups was not significant. Thus present results extend the finding demonstrating that older subjects display an impairment of T cell functions and that IL-2 treatment may correct these alterations. In particular, they confirm the hypothesis that age-associated functional changes are more likely due to diminished numbers of reactive cells, than to a decline in the activity of all cells.

Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1), had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy. Resumo: Duas crianças do sexo masculino com distrofia muscular de Duchenne que contraíram o vírus da gripe pandémica A/H1N1(pH1N1) de 2009 foram tratados com antibióticos e esteróides sem melhoria significativa.Um deles revelou escoliose severa. Depois da hospitalização, um TAC ao peito revelou uma atelectasia pulmonar segmentar bilateral extensa. Os seus resultados clínicos e radiológicos melhoraram rapidamente quando foi adoptado um tratamento de fisioterapia respiratória sequencial, consistente na aplicação de múltiplas sessões de oscilações torácicas de alta frequência, cada uma seguida por exercícios de tosse mecanicamente assistidos. O tratamento foi bem tolerado, eficaz e fácil de aplicar, sendo que não foi necessário um posicionamento especial. Quinze dias depois do início do tratamento, ambos os pacientes se encontravam clinicamente recuperados. Este tratamento pode ser muito útil em pacientes com doenças neuromusculares, particularmente quando a escoliose impede a fisioterapia respiratória convencional. KEYWORDS: Duchenne muscular dystrophy, High frequency chest wall oscillation, Pandemic H1N1 influenza, Atelectasis, : PALAVRAS-CHAVE, Distrofia muscular de Duchenne, Oscilação torácica de alta frequência, Pandemia de gripe H1N1, Atelectasia