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Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Introduction/aimsALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.MethodsThe phase 2B trial enrolled 138 participants within 3 y of symptom onset and with plasma hs-CRP values >1.13 mg/L. They were randomized 1:1 to receive either placebo or NP001 for 6 mo. Change from baseline ALSFRS-R scores was the primary efficacy endpoint. Secondary endpoints included vital capacity (VC) change from baseline and percentage of participants showing no decline of ALSFRS-R score over 6 mo (non-progressor).ResultsThe phase 2B study did not show significant differences between placebo and active treatment with respect to change in ALSFRS-R scores, or VC. The drug was safe and well tolerated. A post hoc analysis identified a 40- to 65-y-old subset in which NP001-treated patients demonstrated slower declines in ALSFRS-R score by 36% and VC loss by 51% compared with placebo. A greater number of non-progressors were NP001-treated compared with placebo (p = .004).DiscussionAlthough the phase 2B trial failed to meet its primary endpoints, post hoc analyses identified a subgroup whose decline in ALSFRS-R and VC scores were significantly slower than placebo. Further studies will be required to validate these findings.

Introduction/aimsALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.MethodsThe phase 2B trial enrolled 138 participants within 3 y of symptom onset and with plasma hs-CRP values >1.13 mg/L. They were randomized 1:1 to receive either placebo or NP001 for 6 mo. Change from baseline ALSFRS-R scores was the primary efficacy endpoint. Secondary endpoints included vital capacity (VC) change from baseline and percentage of participants showing no decline of ALSFRS-R score over 6 mo (non-progressor).ResultsThe phase 2B study did not show significant differences between placebo and active treatment with respect to change in ALSFRS-R scores, or VC. The drug was safe and well tolerated. A post hoc analysis identified a 40- to 65-y-old subset in which NP001-treated patients demonstrated slower declines in ALSFRS-R score by 36% and VC loss by 51% compared with placebo. A greater number of non-progressors were NP001-treated compared with placebo (p = .004).DiscussionAlthough the phase 2B trial failed to meet its primary endpoints, post hoc analyses identified a subgroup whose decline in ALSFRS-R and VC scores were significantly slower than placebo. Further studies will be required to validate these findings.

Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to <60% in nonambulatory patients (p = 0.0004), versus SoC. Ataluren plus SoC delays disease progression and benefits ambulatory and nonambulatory patients with nmDMD. ClinicalTrials.gov registration: NCT01557400.

[Abstract] Introduction. Spinal cord injury is a health problem with great respiratory repercussions, the main cause of morbidity and mortality. Respiratory muscle training (RMT) improves respiratory function and reduces the risk of associated problems. Functional electrostimulation (FES) consists of the application of electrical stimuli to provoque muscles contractions. The aimed of this study is to determine the efficacy of electrostimulation as a method of training the respiratory muscles in spinal cord injuries. Methods. A systematic review was performed. For this, a search was carried out in the main databases in health sciences, and systematic reviews and experimental studies of the last 5 years that investigate the application of FES in the respiratory muscles in spinal cord injuries were selected. A total of 4 studies were located. The main study measures were electrode placement, application parameters (amplitude, duration, and frequency), and respiratory variables (FVC, FEV1, VC, PEM, Pes, Pga, CPF, PEF, MVV, Vt). Results. The placement of the electrodes is very heterogeneous, as well as the application parameters. Although, in some cases the data are contradictory or unclear, the vast majority of the respiratory variables measured show significant changes: FVC (7%), PEM (30%), CPF (55%), PEF (23%). Conclusions. FES appears to improve respiratory function in spinal cord injured patients. However, the scarcity of studies and the sample sizes force us to take these data with caution. Standardization of placement parameters and measured variables is required to reduce variability between studies and thus facilitate comparison of results., [Resumo] Introdución. A lesión medular é un problema de saúde con grandes repercusións respiratorias, principal causa de morbilidade e mortalidade. O adestramento dos músculos respiratorios (RMT) mellora a función respiratoria e reduce o risco de problemas asociados. A electroestimulación funcional (FES) consiste na aplicación de estímulos eléctricos dirixidos á contracción muscular. O obxectivo deste estudo é determinar a eficacia da electroestimulación como método de adestramento dos músculos respiratorios nas lesións medulares. Métodos. Realizouse unha revisión sistemática. Para iso levouse a cabo unha busca nas principais bases de datos en ciencias da saúde, e seleccionáronse revisións sistemáticas e estudos experimentais dos últimos 5 anos que investigan a aplicación da FES nos músculos respiratorios nas lesións medulares. Localizáronse un total de 4 estudos. As principais variables do estudo foron a colocación dos electrodos, os parámetros de aplicación (amplitude, duración e frecuencia) e as variables respiratorias (FVC, FEV1, VC, PEM, Pes, Pga, CPF, PEF, MVV, Vt). Resultados. A colocación dos electrodos é moi heteroxénea, así como os parámetros de aplicación. Aínda que nalgúns casos os datos son contraditorios ou pouco claros, a gran maioría das variables respiratorias medidas presentan cambios significativos: FVC (7%), PEM (30%), CPF (55%), PEF (23%). Conclusións. O EPS parece mellorar a función respiratoria en pacientes lesionados na medula espiñal. Porén, a escaseza de estudos e o tamaño das mostras obrígannos a tomar estes datos con cautela. A estandarización dos parámetros de colocación e das variables medidas é necesaria para reducir a variabilidade entre estudos e facilitar así a comparación de resultados., [Resumen] Introducción. La lesión medular es un problema de salud con grandes repercusiones respiratorias, principal causa de morbimortalidad. El entrenamiento de la musculatura respiratoria (EMR) permite mejorar la función respiratoria y disminuir el riesgo de problemas asociados. La electroestimulación funcional (EEF) consiste en la aplicación de estímulos eléctricos destinados a la contracción muscular. El objetivo de este estudio es determinar la eficacia de la electroestimulación como método de entrenamiento de la musculatura respiratoria en lesionados medulares. Métodos. Se realizó una revisión sistemática. Para ello se llevo a cabo una búsqueda en las principales bases de datos en ciencias de la salud, y se seleccionaron revisiones sistemática y estudios experimentales de los últimos 5 años que investiguen la aplicación de la EEF en la musculatura respiratoria en lesionados medulares. Se localizaron un total de 4 estudios. Las principales variables de estudio fueron la colocación de los electrodos, parámetros de aplicación (amplitud, duración y frecuencia) y variables respiratorias (FVC, FEV1, VC, PEM, Pes, Pga, CPF, PEF, MVV, Vt). Resultados. La colocación de los electrodos es muy heterogénea, así como los parámetros de aplicación. Aunque en algunos casos los datos son contradictorios o poco claros, las variables respiratorias medidas presentan en su gran mayoría cambios significativos: FVC (7%), PEM (30%), CPF (55%), PEF (23%). Conclusiones. La EEF parece mejorar la función respiratoria en los lesionados medulares. Sin embargo, la escasez de estudios y los tamaños muestrales nos obligan a tomar estos datos con cautela. Se requiere de una estandarización de los parámetros de colocación y de las variables medidas para disminuir la variabilidad entre estudios y así facilitar la comparación de resultados.

Background: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions: Even in early-stage Pompe disease, when spirometry results are still within

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. Neurotoxicity is one of its major adverse effects that often demands dose limitation. However, the effects of chronic oxaliplatin on the toxicity of the autonomic nervous system regulating cardiorespiratory function and adaptive reflexes are unknown. Male Sprague Dawley rats were treated with intraperitoneal oxaliplatin (3 mg kg-1 per dose) 3 times a week for 14 days. The effects of chronic oxaliplatin treatment on baseline mean arterial pressure (MAP); heart rate (HR); splanchnic sympathetic nerve activity (sSNA); phrenic nerve activity (PNA) and its amplitude (PNamp) and frequency (PNf); and sympathetic reflexes were investigated in anaesthetised, vagotomised and artificially ventilated rats. The same parameters were evaluated after acute oxaliplatin injection, and in the chronic treatment group following a single dose of oxaliplatin. The amount of platinum in the brain was determined with atomic absorption spectrophotometry. Chronic oxaliplatin treatment significantly increased MAP, sSNA and PNf and decreased HR and PNamp, while acute oxaliplatin had no effects. Platinum was accumulated in the brain after chronic oxaliplatin treatment. In the chronic oxaliplatin treatment group, further administration of a single dose of oxaliplatin increased MAP and sSNA. The baroreceptor sensitivity and somatosympathetic reflex were attenuated at rest while the sympathoexcitatory response to hypercapnia was increased in the chronic treatment group. This is the first study to reveal oxaliplatin-induced alterations in the central regulation of cardiovascular and respiratory functions as well as reflexes that may lead to hypertension and breathing disorders which may be mediated via accumulated platinum in the brain.Copyright © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. Neurotoxicity is one of its major adverse effects that often demands dose limitation. However, the effects of chronic oxaliplatin on the toxicity of the autonomic nervous system regulating cardiorespiratory function and adaptive reflexes are unknown. Male Sprague Dawley rats were treated with intraperitoneal oxaliplatin (3 mg kg-1 per dose) 3 times a week for 14 days. The effects of chronic oxaliplatin treatment on baseline mean arterial pressure (MAP); heart rate (HR); splanchnic sympathetic nerve activity (sSNA); phrenic nerve activity (PNA) and its amplitude (PNamp) and frequency (PNf); and sympathetic reflexes were investigated in anaesthetised, vagotomised and artificially ventilated rats. The same parameters were evaluated after acute oxaliplatin injection, and in the chronic treatment group following a single dose of oxaliplatin. The amount of platinum in the brain was determined with atomic absorption spectrophotometry. Chronic oxaliplatin treatment significantly increased MAP, sSNA and PNf and decreased HR and PNamp, while acute oxaliplatin had no effects. Platinum was accumulated in the brain after chronic oxaliplatin treatment. In the chronic oxaliplatin treatment group, further administration of a single dose of oxaliplatin increased MAP and sSNA. The baroreceptor sensitivity and somatosympathetic reflex were attenuated at rest while the sympathoexcitatory response to hypercapnia was increased in the chronic treatment group. This is the first study to reveal oxaliplatin-induced alterations in the central regulation of cardiovascular and respiratory functions as well as reflexes that may lead to hypertension and breathing disorders which may be mediated via accumulated platinum in the brain.Copyright © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler (R) device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler (R) device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases.

Bronchial asthma (BA) is characterized by chronic inflammation of the respiratory tract, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, along with variable airway obstruction [1]. AD is one of the most common diseases of the respiratory tract. &nbsp

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler (R) device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases.

Background: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions: Even in early-stage Pompe disease, when spirometry results are sti

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler (R) device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler (R) device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases.

Background: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions: Even in early-stage Pompe disease, when spirometry results are sti

Background: Peak expiratory flow (PEF) and walking speed (WS) have been proposed as indicators of robustness and are independent predictors of health-related outcomes. We aimed to investigate how the co-occurrence of respiratory and physical impairments changes as a function of age, and to quantify the association of the combination of low PEF and slow WS on survival in older people. Methods: This prospective study analyzes data from 2656 community-dwelling participants (age >= 60 years) from the SNAC-K study. At baseline, we assessed: (1) sociodemographic, lifestyle and medical data; (2) respiratory function, estimated through PEF and expressed as standardized residual (SR) percentile; and (3) WS at usual pace, categorized as no (> 1.2 m/s), mild (0.8-1.2 m/s) and moderate-to-severe (< 0.8 m/s) walking impairment. Participants' vital status over an 18-year follow-up was derived from registers. The association of different combinations of PEF and WS on median survival time was estimated through Laplace regression adjusted for potential confounders. Results: Respiratory and walking impairments co-occurred more frequently with increasing age. Among individuals with PEF SR-percentiles < 10th, the percentage of moderate-to-severe walking impairment was 12.1% in sexagenarians, 35.7% in septuagenarians, and 75-80% in the oldest old. The greatest reduction in median survival time (- 5.4 [95%CI: -6.4; -4.4] years, p < 0.001) was observed among people with combined respiratory and moderate-to-severe walking impairments, compared with those with no dysfunctions, who had a median survival time of 17.4 (95%CI: 17.0; 17.8) years. Conclusions: Impaired PEF and WS co-occur more frequently with advancing age, and their co-occurrence is associated with shorter survival.

Background and objective: Frequent central apnoeas are sometimes observed in healthy children; however; the pathophysiology of an elevated central apnoea index (CAI) is poorly understood. A raised CAI may indicate underlying ventilatory control instability (i.e. elevated loop gain, LG) or a depressed ventilatory drive. This pilot study aimed to compare LG in otherwise healthy children with an elevated CAI to healthy controls. Method(s): Polysomnographic recordings from children (age > 6 months) without obstructive sleep apnoea and with a CAI > 5 events/h (n = 13) were compared with age and gender-matched controls with a CAI < 5 events/h (n = 13). Spontaneous sighs were identified during non-rapid eye movement (NREM) sleep, and breath-breath measurements of ventilation were derived from the nasal pressure signal. A standard model of ventilatory control (gain, time constant and delay) was used to calculate LG by transforming ventilatory fluctuations seen in response to a sigh into a ventilatory-drive signal that best matches observed ventilation. Result(s): The high CAI group had an elevated LG (median = 0.36 (interquartile range, IQR = 0.35-0.53) vs 0.28 (0.23-0.36); P <= 0.01). There was no difference in either the time constant (P = 0.63) or delay (P = 0.29) between groups. Elevated LG observed in the high CAI group remained after accounting for degree of hypoxia (average oxygen saturation (SpO2) during each analysable window) experienced (0.40 (0.30-0.53) vs 0.25 (0.23-0.37); P = 0.04). Conclusion(s): An elevated CAI in otherwise healthy children is associated with a raised LG compared to matched controls with a low CAI, irrespective of level of hypoxia. This relative ventilatory instability helps explain the high CAI and may ultimately be able to help guide diagnosis and management in patients with high CAI.Copyright © 2019 Asian Pacific Society of Respirology

Objective Higher rates of neonatal morbidity and mortality at term combined with earlier spontaneous delivery have led to the hypothesis that babies born to South Asian born (SA-born) women may mature earlier and/or their placental function decreases earlier than babies born to Australian and New Zealand born (Aus/NZ-born) women. Whether babies born to SA-born women do better in the preterm period, however, has yet to be evaluated. In this study we investigated respiratory outcomes, indicative of functional maturity, of preterm babies born to SA-born women compared with those of Aus/NZ-born women to explore this hypothesis further. Study design and setting This retrospective cohort study was conducted at Monash Health. Patients Data were collected from neonatal and birth records of moderate-late preterm (32-36 weeks) infants born between 2012 and 2015 to SA-born and Aus/NZ-born women. Outcome measures Rates of nursery admissions and neonatal respiratory outcomes were compared. Results Babies born to Aus/NZ-born women were more likely to be admitted to a nursery (80%) compared with SA-born babies (72%, p=0.004). Babies born to SA-born mothers experienced significantly less hyaline membrane disease (7.8%), required less resuscitation at birth (28.6%) and were less likely to require ventilation (20%) than babies born to Aus/NZ-born mothers (18%, 42.2%, 34.6%; p<0.001). There was no difference in the duration of ventilation or length of stay in hospital. Conclusions Moderate-late preterm babies born to SA-born women appear to have earlier functional maturity, as indicated by respiratory outcomes, than Aus/NZ-born babies. Our findings support the hypothesis of earlier fetal maturation in SA-born women.Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Objective: To examine respiratory muscle function among late-onset Pompe disease (LOPD) patients in the Pompe Registry (NCT00231400/Sanofi Genzyme) during enzyme replacement therapy (ERT) with alglucosidase alfa by assessing the longitudinal course of forced vital capacity (FVC), prognostic factors for FVC, and impact of time from diagnosis to ERT initiation. Methods: Longitudinal FVC data from LOPD (symptom onset > 12 months or ≤ 12 months without cardiomyopathy) patients were analyzed. Patients had to have baseline FVC (percent predicted upright) assessments at ERT start and ≥ 2 valid post-baseline assessments. Longitudinal analyses used linear mixed-regression models. Results: Among 396 eligible patients, median baseline FVC was 66.9% (range 9.3–126.0). FVC remained stable during the 5-year follow-up (slope = − 0.17%, p = 0.21). Baseline FVC was lower among various subgroups, including patients who were male; older at ERT initiation; had a longer duration from symptom onset to ERT initiation; and had more advanced disease at baseline (based on respiratory support use, inability to ambulate, ambulation device use). Age at symptom onset was not associated with baseline degree of respiratory dysfunction. Differences between subgroups observed at baseline remained during follow-up. Shorter time from diagnosis to ERT initiation was associated with higher FVC after 5 years in all patients and the above subgroups using a cut-off of 1.7 years. Conclusion: FVC stability over 5 years suggests that respiratory function is preserved during long-term ERT in real-world settings. Early initiation of alglucosidase alfa was associated with preservation of FVC in LOPD patients with better respiratory function at the time of treatment initiation.

Background and objective: Frequent central apnoeas are sometimes observed in healthy children; however; the pathophysiology of an elevated central apnoea index (CAI) is poorly understood. A raised CAI may indicate underlying ventilatory control instability (i.e. elevated loop gain, LG) or a depressed ventilatory drive. This pilot study aimed to compare LG in otherwise healthy children with an elevated CAI to healthy controls. Method(s): Polysomnographic recordings from children (age > 6 months) without obstructive sleep apnoea and with a CAI > 5 events/h (n = 13) were compared with age and gender-matched controls with a CAI < 5 events/h (n = 13). Spontaneous sighs were identified during non-rapid eye movement (NREM) sleep, and breath-breath measurements of ventilation were derived from the nasal pressure signal. A standard model of ventilatory control (gain, time constant and delay) was used to calculate LG by transforming ventilatory fluctuations seen in response to a sigh into a ventilatory-drive signal that best matches observed ventilation. Result(s): The high CAI group had an elevated LG (median = 0.36 (interquartile range, IQR = 0.35-0.53) vs 0.28 (0.23-0.36); P <= 0.01). There was no difference in either the time constant (P = 0.63) or delay (P = 0.29) between groups. Elevated LG observed in the high CAI group remained after accounting for degree of hypoxia (average oxygen saturation (SpO2) during each analysable window) experienced (0.40 (0.30-0.53) vs 0.25 (0.23-0.37); P = 0.04). Conclusion(s): An elevated CAI in otherwise healthy children is associated with a raised LG compared to matched controls with a low CAI, irrespective of level of hypoxia. This relative ventilatory instability helps explain the high CAI and may ultimately be able to help guide diagnosis and management in patients with high CAI.Copyright © 2019 Asian Pacific Society of Respirology

Objective Higher rates of neonatal morbidity and mortality at term combined with earlier spontaneous delivery have led to the hypothesis that babies born to South Asian born (SA-born) women may mature earlier and/or their placental function decreases earlier than babies born to Australian and New Zealand born (Aus/NZ-born) women. Whether babies born to SA-born women do better in the preterm period, however, has yet to be evaluated. In this study we investigated respiratory outcomes, indicative of functional maturity, of preterm babies born to SA-born women compared with those of Aus/NZ-born women to explore this hypothesis further. Study design and setting This retrospective cohort study was conducted at Monash Health. Patients Data were collected from neonatal and birth records of moderate-late preterm (32-36 weeks) infants born between 2012 and 2015 to SA-born and Aus/NZ-born women. Outcome measures Rates of nursery admissions and neonatal respiratory outcomes were compared. Results Babies born to Aus/NZ-born women were more likely to be admitted to a nursery (80%) compared with SA-born babies (72%, p=0.004). Babies born to SA-born mothers experienced significantly less hyaline membrane disease (7.8%), required less resuscitation at birth (28.6%) and were less likely to require ventilation (20%) than babies born to Aus/NZ-born mothers (18%, 42.2%, 34.6%; p<0.001). There was no difference in the duration of ventilation or length of stay in hospital. Conclusions Moderate-late preterm babies born to SA-born women appear to have earlier functional maturity, as indicated by respiratory outcomes, than Aus/NZ-born babies. Our findings support the hypothesis of earlier fetal maturation in SA-born women.Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Lipids constitute a significant group of biological metabolites and the building blocks of all cell membranes. The abundance and stoichiometries of different lipid species are known to vary across the lifespan and metabolic state, yet the functional effects of these changes have been challenging to understand. Here we review the potentially powerful intersection of lipid metabolism, which determines membrane composition, and aging. We first introduce several key lipid classes that are associated with aging and aging-related disease, where they are found in organisms, and how they act on membrane structure and function. Instead of neutral lipids, which have primary roles in energy storage and homeostasis, we review known functions for polar lipids that control the physicochemical properties of cell membranes. We then focus on aging processes in the central nervous system (CNS), which is enriched in lipids and is highly dependent on membrane structure for function. Recent studies show how lipids act not just as biomarkers of aging and associated changes in the CNS, but as direct mediators of these processes. As a model system, we explore how fatty acid composition in the retina impact aging and aging-related disease. We propose that the biophysical effects of membrane structure on fundamental eukaryotic processes - mitochondrial respiration and autophagy - provide avenues by which lipid dysregulation can accelerate aging processes. Finally, we lay out ways in which an increased understanding of lipid membrane biology can be applied to studies of aging and lifespan.

Isolated breathing training in rehabilitation and voice training is a common practice in Spanish-speaking countries. Currently, there are no documents in Spanish that study the theoretical and empirical information related to respiratory training in this context. The purpose of the present review is to provide updated information regarding the current evidence of the possible effect of isolated respiratory training on voice. Respiratory strength training has been shown to have positive effects on respiratory parameters, however, the available evidence does not report significant effects on the voice, except for people with underlying neurological disorders and presbyphonia. If respiratory training using devices designed for these purposes has not been shown to positively impact vocal characteristics of subjects with dysphonia (not neurological or presbyphonia) or of healthy professional voice users, there is no reason to expect that the isolated breathing exercises that are often included in the routines of vocal trainers and speech therapists will have a positive effect on voice variables. Considering that respiratory muscle strength training seems to positively affect some vocal parameters in people with neurological disorders and presbyphonia, future research should consider exploring the possible effect on other vocal parameters not yet measured in this type of population., La implementación del entrenamiento respiratorio aislado en la rehabilitación y el entrenamiento de la voz es una práctica común en los países de habla hispana. Actualmente, no existe ningún manuscrito en español que revise la información teórica y empírica del entrenamiento respiratorio en este contexto. El propósito de la presente revisión es entregar la evidencia actualizada del efecto del entrenamiento respiratorio aislado en la voz. El entrenamiento de la fuerza respiratoria ha demostrado tener consecuencias positivas en los parámetros medidos; no obstante, los datos disponibles hasta ahora no reporta efectos significativos en la voz, exceptuando los casos de personas con trastornos neurológicos de base y presbifonía. Si el entrenamiento respiratorio con el uso de dispositivos no ha demostrado impactar favorablemente sobre otras disfonías (no neurológicas ni presbifonía) ni en sujetos sanos profesionales de la voz, no existiría razón para esperar que los ejercicios respiratorios aislados que se suelen incluir en las rutinas de entrenadores vocales, fonoaudiólogos, logopedas y foniatras tengan un efecto positivo. Considerando que el entrenamiento de la fuerza muscular respiratoria parece actuar sobre algunos parámetros vocales en personas con alteraciones neurológicas y presbifonía, futuras investigaciones deberían considerar la exploración del posible efecto positivo en otros parámetros vocales no medidos aún en este tipo de población.

Objective To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy.Study design Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry.Results Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) >= 6 hours. In those less than 2 years old, only 3 patients shifted from NIV <= 10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV <= 10 hours.Conclusions Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support >= 16 hours, especially before the age of 2 years.

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.

Objective: To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy. Study design: Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry. Results: Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) ≥16 hours. In those less than 2 years old, only 3 patients shifted from NIV ≤10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV ≤10 hours. Conclusions: Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support ≥16 hours, especially before the age of 2 years.

Chronic obstructive pulmonary disease (COPD) still remains a serious problem for the public health care system, since it commonly causes disability and mortality among the working population. Frequent combination of COPD with concomitant diseases is a key factor in predicting COPD consequences. Recently, the number of patients with a combination of COPD and overweight is on the increase, which is considered as a mutual aggravating factor and negatively affects the prognosis of the disease in such patients. The objective of this study was to investigate the diagnostic value of leptin in progression of COPD (III degree of bronchial obstruction in patients with overweight) course by studying its level in blood serum. Materials and methods: There were examined 112 patients with chronic obstructive pulmonary disease (COPD GOLD III) in different phases of pathological process. The pulmonary function (PF) test was performed by means of “SPIROKOM” device (Ukraine). The degree of overweight was determined by calculating the body mass index (BMI) using the formula І = m/h² (m – body mass in kilograms, h – height, in square meters (kg/m²). The level of leptin of systemic inflammatory markers was determined by a solid phase enzyme-linked immunosorbent assay in blood serum: “DRG Leptin Elisa” (Germany). Results and conclusions: The study revealed that overweight leads to a more severe course of COPD (III degree of bronchial obstruction), and the determination of leptin may serve as a diagnostic criterion in the progression of this pathology.

Objective To determine the variability of primary and secondary outcomes used in trials of intravenous bronchodilators in children with acute severe paediatric asthma. Methods Systematic search of MEDLINE, EMBASE, Cochrane CENTRAL and the WHO International Clinical Trials Registry Platform for randomised trials in children (less than18 years) with acute severe paediatric asthma comparing intravenous bronchodilator therapy to another treatment. Initial search was performed on 7 January 2016 with an updated search performed on 6 September 2018. Primary and secondary outcomes were collated. Results We identified 35 published papers and four registered study protocols. 56 primary outcomes were found, the most common being a clinical asthma score (23/56; 41%). Other identified primary outcomes included bedside tests of respiratory function (11/56; 20%) and measures of length of stay (9/56; 16%). There were a total of 60 different secondary outcomes, the most common were various length of stay measures (24/60; 40%) and adverse events (11/60; 18%). Conclusion Studies comparing intravenous treatment modalities for children with acute severe paediatric asthma exhibit great variation in the type, number and timing of outcome measures used. There are no patient or family-specific outcomes reported. There is a need to develop international consensus.Copyright © 2019 Author(s) (or their employer(s)).

Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families.Copyright © 2019 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians)

Objective To determine the variability of primary and secondary outcomes used in trials of intravenous bronchodilators in children with acute severe paediatric asthma. Methods Systematic search of MEDLINE, EMBASE, Cochrane CENTRAL and the WHO International Clinical Trials Registry Platform for randomised trials in children (less than18 years) with acute severe paediatric asthma comparing intravenous bronchodilator therapy to another treatment. Initial search was performed on 7 January 2016 with an updated search performed on 6 September 2018. Primary and secondary outcomes were collated. Results We identified 35 published papers and four registered study protocols. 56 primary outcomes were found, the most common being a clinical asthma score (23/56; 41%). Other identified primary outcomes included bedside tests of respiratory function (11/56; 20%) and measures of length of stay (9/56; 16%). There were a total of 60 different secondary outcomes, the most common were various length of stay measures (24/60; 40%) and adverse events (11/60; 18%). Conclusion Studies comparing intravenous treatment modalities for children with acute severe paediatric asthma exhibit great variation in the type, number and timing of outcome measures used. There are no patient or family-specific outcomes reported. There is a need to develop international consensus.Copyright © 2019 Author(s) (or their employer(s)).

Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families.Copyright © 2019 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians)

Background: Chronic Obstructive Pulmonary Disease (COPD) encompasses various phenotypes that severely limit the applicability of precision respiratory medicine. The present investigation is aimed to assess the circadian rhythm of symptoms in pre-defined clinical COPD phenotypes and its association with health-related quality of life (HR-QoL), the quality of sleep and the level of depression/anxiety in each clinical phenotype. Methods: The STORICO (NCT03105999) Italian observational prospective cohort study enrolled COPD subjects. A clinical diagnosis of either chronic bronchitis (CB), emphysema (EM) or mixed COPD-asthma (MCA) phenotype was made by clinicians at enrollment. Baseline early-morning, day-time and nocturnal symptoms (gathered via the Night-time, Morning and Day-time Symptoms of COPD questionnaire), HR-QoL (via the St. George's Respiratory Questionnaire), anxiety and depression levels (via the Hospital Anxiety and Depression Scale), quality of sleep (via COPD and Asthma Sleep Impact Scale), physical activity (via the International Physical Activity Questionnaire) as well as lung function were recorded. Results: 606 COPD subjects (age 71.4 ± 8.2 years, male 75.1%) were studied. 57.9, 35.5 5.3 and 1.3% of the sample belonged to the CB, EM, MCA and EM + CB phenotypes respectively. The vast majority of subjects reported early-morning and day-time symptoms (79.5 and 79.2% in the CB and 75.8 and 77.7% in the EM groups); the proportion suffering from night-time symptoms was higher in the CB than in the EM group (53.6% vs. 39.5%, p = 0.0016). In both CB and EM, indiscriminately, the presence of symptoms during the 24-h day was associated with poorer HR-QoL, worse quality of sleep and higher levels of anxiety/depression. Conclusions: The findings highlight the primary classificatory role of nocturnal symptoms in COPD. Trial registration: Trial registration number: NCT03105999, date of registration: 10th April 2017.