Precision in Practice: Enhancing MI-E Therapy Evaluation for Improved Patient Outcomes, Excluding Speech and Swallowing. Reply to Allen et al. Comment on "Chatwin et al. Waves of Precision: A Practical Guide for Reviewing New Tools to Evaluate Mechanical In-Exsufflation Efficacy in Neuromuscular Disorders. J. Clin. Med. 2024, 13, 2643".

We would like to thank Allen et al [...].

Upper Airway and Translaryngeal Resistance During Mechanical Insufflation-Exsufflation.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) uses positive and negative pressures to assist weak cough and to help clear airway secretions. Laryngeal visualization during MI-E has revealed that inappropriate upper airway responses can impede its efficacy. However, the dynamics of pressure transmission in the upper airways during MI-E are unclear, as are the relationships among anatomic structure, pressure, and airflow. RESEARCH QUESTION: Can airflow resistance through the upper airway and the larynx feasibly be calculated during MI-E, and if so, how are the pressures transmitted to the trachea? STUDY DESIGN AND METHODS: Cross-sectional study of 10 healthy adults with and without active cough to whom MI-E was provided, using pressure settings +20/-40 cm H2O and ± 40 cm H2O. Airflow and pressure at the level of the facemask were measured using a pneumotachograph, whereas pressure transducers (positioned via transnasal fiber-optic laryngoscopy) recorded pressures above the larynx and within the trachea. Upper airway resistance (Ruaw) and translaryngeal resistance (Rtl) were calculated (in centimeters of water per liter per second) and were compared with direct observations via laryngoscopy. RESULTS: Positive pressures reached the trachea effectively, whereas negative tracheal pressures during exsufflation were approximately half of the intended settings. Insufflation pressure increased slightly when passing through the larynx. Participant effort influenced tracheal pressures and the resistances, with findings consistent with laryngoscopic observations. During MI-E, resistance seems to be dynamic, with Ruaw exceeding Rtl. Inappropriate laryngeal closure increased Rtl during both positive and negative pressures. INTERPRETATION: Ruaw and Rtl can be calculated feasibly during MI-E. The findings indicate different transmission dynamics for positive and negative pressures and that resistances are influenced by participant effort. The findings support using lower insufflation pressures and higher negative pressures in clinical practice.

Airway Clearance in Neuromuscular Disease.

High-quality respiratory care and airway clearance is essential for people with neuromuscular disease (pwNMD) as respiratory tract infections are a major cause of morbidity and mortality. This review expands on published guidelines by highlighting the role of cough peak flow along with other options for cough evaluation, and discusses recent key research findings which have influenced the practice of respiratory therapy for pwNMD.

Effects of high-flow nasal therapy on swallowing function: a scoping review.

Background: High-flow nasal therapy is widely used in patients with respiratory failure in different clinical settings, but the effect of high-flow nasal therapy on respiratory-swallow coordination is unknown. Understanding this relationship is crucial, considering the necessity for patients to maintain adequate nutrition during daytime high-flow nasal therapy. This scoping review aims to synthesise available data on the effects of high-flow nasal therapy flow rates on swallowing function and the possible risk of aspiration during treatment, focusing on knowledge and evidence gaps. Methods: PubMed, Scopus, Web of Science and Google Scholar databases were searched from inception to 30 May 2023 for studies reporting data on swallowing assessment in healthy adults or patients with acute or chronic respiratory failure receiving high-flow nasal therapy. Data on study design, patients' characteristics and quality outcomes were extracted. Results: Eight studies were included, four including cohorts of healthy volunteers (n=148) and four including patients with acute or chronic respiratory failure (n=151). Study designs, patient populations and quality outcome measures were heterogeneous. Two studies indicated improvement while four articles showed impairment in swallowing function during high-flow nasal therapy; two studies showed that patients' overall clinical picture and underlying medical conditions influenced swallowing-breathing coordination rather than high-flow nasal therapy per se. Conclusion: This scoping review found limited and controversial evidence on the impact of high-flow nasal therapy on swallowing function. Remarkably, methods for swallowing function assessment were quite heterogeneous. Additional research is required to test the effect of high-flow nasal therapy on respiratory-swallowing coordination.

Practical recommendations for swallowing and speaking during NIV in people with neuromuscular disorders.

Objectives: The functions of eating, drinking, speaking, and breathing demand close coordination of the upper airway musculature which may be challenged by the long-term use of daytime non-invasive ventilation (NIV). This rapid review explores the challenges and practicalities of these interactions in people with neuromuscular disorders. Methods: A search was performed on PubMed (period 2000-2023) using generic terms to refer to eating, drinking, and speaking related to people with neuromuscular disorders on NIV. A narrative approach was used to summarize the available literature. Results: Our review shows only a small number of studies exist exploring the use of NIV on swallowing and speaking in people with neuromuscular disorders. We summarize study findings and provide practical advice on eating, drinking and speaking with NIV. Conclusions: By understanding breathing, NIV mechanics and upper airway interactions, it is possible to optimize swallowing and speaking whilst using NIV. There is a lack of specific guidelines, and concerns regarding aspiration warrant further research and guideline development.

Waves of Precision: A Practical Guide for Reviewing New Tools to Evaluate Mechanical In-Exsufflation Efficacy in Neuromuscular Disorders.

Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate cough effectiveness with and without MI-E. This review highlights the limitations of this and discussed other tools to evaluate MI-E efficacy in this rapidly developing field. Such tools include the interpretation of parameters (like pressure, flow and volumes) that derive from the MI-E device and external methods to evaluate upper airway closure. In this review we pinpoint the differences between different devices in the market and discuss new tools to better titrate MI-E and detect pathological responses of the upper airway. We discuss the importance of point of care ultrasound (POCUS), transnasal fiberoptic laryngoscopy and wave form analysis in this setting. To improve clinical practice newer generation MI-E devices should allow real-time evaluation of waveforms and standardize some of the derived parameters.

Experiences of individually tailored physical exercise in boys with Duchenne muscular dystrophy: a qualitative study.

INTRODUCTION: Excessive and insufficient physical exercise have both been associated with accelerated muscle function decline in boys with Duchenne Muscular Dystrophy (DMD), and optimal exercise remains unclear. OBJECTIVE: This study explored participants' experiences with a one-year training program. METHODS: Five semi-structured qualitative individual interviews and one focus group interview were conducted and analyzed using systematic text condensation. RESULTS: Participants included boys with DMD who participated in the intervention study (n = 10), their relatives and/or assistants (n = 7). Four main themes emerged: 1) the crucial role of motivation to maintain training routines, 2) benefiting from exercise, but with a need for balancing it, 3) time management challenges, and 4) the training as a social arena and meeting place. The participants emphasized the importance of experiencing progress, basic skills and enjoyable training. Parents were reassured knowing the appropriate exercise intensity and technique. The boys needed flexibility and support to find a balance between exercise and other activities and described benefits from sharing experiences with each other. CONCLUSION: Clinical guidelines for physical exercise in DMD should encompass customization of exercise interventions supporting motivational factors, balance and social interaction, and identify competing commitments. Successful training programs may enhance quality of life and functionality for these boys.

Mechanically assisted cough strategies: user perspectives and cough flows in children with neurodisability.

Background: Mechanical insufflation-exsufflation (MI-E) is used to augment cough in children with neurodisability. We aimed to determine the user comfort and cough flows during three MI-E strategies, and to predict factors associated with improved comfort and cough flows. Methods: This multicentre, crossover trial was done at four regional hospitals in Norway. Children with neurodisability using MI-E long term via mask were enrolled. In randomised order, they tested three MI-E setting strategies (in-/exsufflation pressure (cmH2O)/in (In)- versus exsufflation (Ex) time): 1) "A-symmetric" (±50/In=Ex); 2) "B-asymmetric" (+25- +30)/-40, In>Ex); and 3) "C-personalised", as set by their therapist. The primary outcomes were user-reported comfort on a visual analogue scale (VAS) (0=maximum comfort) and peak cough flows (PCF) (L·min-1) measured by a pneumotachograph in the MI-E circuit. Results: We recruited 74 children median (IQR) age 8.1 (4.4-13.8) years, range 0.6-17.9, and analysed 218 MI-E sequences. The mean±sd VAS comfort scores were 4.7±2.96, 2.9±2.44 and 3.2±2.46 for strategies A, B and C, respectively (A versus B and C, p<0.001). The mean±sd PCF registered during strategies A, B and C were 203±46.87, 166±46.05 and 171±49.74 L·min-1, respectively (A versus B and C, p<0.001). Using low inspiratory flow predicted improved comfort. Age and unassisted cough flows increased exsufflation flows. Conclusions: An asymmetric or personalised MI-E strategy resulted in better comfort scores, but lower PCF than a symmetric approach utilising high pressures. All three strategies generated cough flows above therapeutic thresholds and were rated as slightly to moderately uncomfortable.

Norwegian Version of the Chelsea Critical Care Physical Assessment Tool (CPAx-NOR): Translation, Face Validity, Cross-Cultural Adaptation and Inter-Rater Reliability.

BACKGROUND: Assessment of physical and respiratory function in the intensive care unit (ICU) is useful for developing an individualized treatment plan and evaluating patient progress. There is a need for measurement tools that are culturally adapted, reliable and easy to use. The Chelsea Critical Care Physical Assessment Tool (CPAx) is a valid measurement tool with strong psychometric properties for the intensive care population. This study aims to translate, adapt and test face validity and inter-rater reliability of the Norwegian version of CPAx (CPAx-NOR) for use in critically ill adult patients receiving prolonged mechanical ventilation. METHOD: CPAx-NOR was forward backward translated, culturally adapted and tested by experts and patients for face validity. Thereafter tested by 10 physiotherapists in five hospitals for inter-rater reliability. RESULTS: The experts and pilot testers reached consensus on the translation and face validity. Patients were tested at time point A (n = 57) and at time point B (n = 53). The reliability of CPAx-NOR at "A" was 0.990 (0.983-0.994) and at "B" 0.994 (0.990-0.997). Based on A+B combined and adjusted, the ICC was 0.990 (95% CI 0.996-0.998). Standard error of measurement (SEM) was 0.68 and the minimal detectable change (MDC) was 1.89. The Bland-Altman plot showed low bias and no sign of heteroscedasticity. CPAx-NOR changed with a mean score of 14.9, and showed a moderate floor effect at the start of physiotherapy and low ceiling effects at discharge. CONCLUSION: CPAx-NOR demonstrated good face validity and excellent inter-rater reliability. It can be used as an assessment tool for physical function in critically ill adults receiving prolonged mechanical ventilation in Norway.

Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma. METHODS AND ANALYSIS: The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80-120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences. TRIAL REGISTRATION NUMBER: NCT04593394.

User-perceived impact of long-term mechanical assisted cough in paediatric neurodisability.

AIM: To (1) compare the perceived benefit of long-term mechanical insufflation-exsufflation (MI-E) of children with neuromuscular disorders (NMDs) and central nervous system (CNS) disorders, including health care needs and treatment routines and (2) describe the children's health-related quality of life (HRQoL). METHOD: This cross-sectional study used a questionnaire and memory card data to assess the perceived benefit of MI-E via the Visual Analogue Scale (VAS; 10 maximum), willingness to pause treatment, level of health care needs before and after MI-E initiation, and the children's treatment routines. A DISABKIDS questionnaire assessed HRQoL (100 maximum). RESULTS: Seventy-three children using MI-E participated (42 males, median [interquartile range {IQR}] age 10 years 2 months [6 years 3 months-14 years 1 month]), 47 with NMDs (such as spinal muscular atrophy and Duchenne muscular dystrophy) and 26 with CNS disorders (such as cerebral palsy, encephalitis, neurometabolic and other diseases). The median (IQR) VAS score for the perceived benefit of MI-E therapy at stable state and respiratory tract infection were 9 (6-10) and 10 (8.5-10) respectively. Sixty-two per cent were reluctant or unwilling to pause MI-E therapy, with no NMD versus CNS disorder group difference. After MI-E initiation, fewer physician consultations and hospitalizations were reported by the group with NMDs. The MI-E routine was similar in both groups. The mean (SD) HRQoL score for 26 of 51 eligible children was 71 (16.7). INTERPRETATION: MI-E treatment was generally perceived as beneficial and performed equally in both diagnostic groups. HRQoL was in line with children with a moderate-to-severe chronic condition. WHAT THIS PAPER ADDS: Mechanical insufflation-exsufflation (MI-E) was generally perceived as beneficial by the children and parents. The reported benefit of MI-E was higher among daily than sporadic MI-E users. The MI-E treatment routine did not differ between diagnostic groups. The health-related quality of life in this neuropaediatric population was in line with that of children with other moderate-to-severe chronic conditions.

Upper airway assessment and its implications for interventions by respiratory physiotherapists.

BACKGROUND: When noninvasive interventions such as chest physiotherapy fail, then more aggressive interventions for airway secretion clearance with nasotracheal airway suctioning may be required. Clinicians however have to insert the nasotracheal suction catheter "blindly" and the success of being able to trigger a cough and pass through the vocal folds with a suction catheter is low. CASE DESCRIPTION: The patient, a 48-year-old male underwent a heart and lung transplant. Following extubation, the patient developed secretion retention with a weak ineffective cough and swallow and required physiotherapy interventions with frequent "blind" passes of nasotracheal suctioning. OUTCOMES: The patient required nasotracheal suction with frequent multiple failed attempts before successful passage of the suction catheter to trigger a cough reflex and clear secretions. A combined physiotherapist and speech and language therapist intervention during fiberoptic endoscopic evaluation of swallow (FEES) was recorded to both evaluate swallow and passage of the suction catheter. The video illustrated the successful passage of a suctioning catheter through the vocal folds leading to an effective cough and airway clearance. DISCUSSION: We present a case report demonstrating that it is feasible to visualize the upper airways during nasotracheal suctioning as an objective means to guide the more accurate successful insertion of the suction catheter past the vocal folds. Rather than "blind" placement of nasotracheal suction catheters visualization using transnasal laryngoscopy should be useful to increase chances of passing through the vocal folds.

Exercise Training in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.

OBJECTIVE:  To evaluate the effects and safety of exercise training, and to determine the most effective exercise intervention for people with Duchenne muscular dystrophy. Exercise training was compared with no training, placebo or alternative exercise training. Primary outcomes were functioning and health-related quality of life. Secondary outcomes were muscular strength, endurance and lung function.  Data sources: A systematic literature search was conducted in Medline, EMBASE, CINAHL, Cochrane Central, PEDro and Scopus.  Study selection and data extraction: Screening, data extraction, risk of bias and quality assessment were carried out. Risk of bias was assessed using the Cochrane Collaborations risk of bias tools. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. DATA SYNTHESIS: Twelve studies with 282 participants were included. A narrative synthesis showed limited or no improvements in functioning compared with controls. Health-related quality of life was assessed in only 1 study. A meta-analysis showed a significant difference in muscular strength and endurance in favour of exercise training compared with no training and placebo. However, the certainty of evidence was very low. CONCLUSION: Exercise training may be beneficial in Duchenne muscular dystrophy, but the evidence remains uncertain. Further research is needed on exercise training to promote functioning and health-related quality of life in Duchenne muscular dystrophy.

Adjustments of non-invasive ventilation and mechanically assisted cough by combining ultrasound imaging of the larynx with transnasal fibre-optic laryngoscopy: a protocol for an experimental study.

INTRODUCTION: Application of non-invasive positive airway pressure may provoke laryngeal responses that obstruct the airways, especially in patients with disturbed laryngeal control. To control and adjust for this, transnasal fibre-optic laryngoscopy (TFL) is used to visualise laryngeal movements during therapeutic interventions. Being an invasive procedure, this may be unpleasant for patients. The aim of this study is to evaluate if ultrasound (US) imaging of the larynx may be used as an alternative less invasive diagnostic tool for evaluating the upper airway responses to non-invasive ventilation (NIV) and mechanical insufflation-exsufflation (MI-E). METHODS AND ANALYSIS: This protocol presents an experimental cross-sectional study of a novel method to study laryngeal responses in adult healthy volunteers (n=30). The participants will be assessed with simultaneous TFL and laryngeal US imaging (anterior and lateral approaches) during NIV and MI-E therapy. Additionally, airflow and pressure signals will be registered during the procedures. The primary outcome is whether laryngeal US is a feasible method to study laryngeal responses and, if so, to compare the laryngeal responses visualised with TFL and US. The participants' perception of the examinations will be recorded. Secondary outcomes include airflow curve shapes and calculated ventilation volumes during the interventions. ETHICS AND DISSEMINATION: The study has been approved by The Regional Committee for Medical Research Ethics in Norway, and registered in ClinicalTrials.gov. Results will be disseminated through peer-reviewed journals, presentation of scientific abstracts at international medical conventions and oral presentations in relevant medical conventions. TRIAL REGISTRATION NUMBER: NCT04586855.

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

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

Reliability of translaryngeal airway resistance measurements during maximal exercise.

Objective: Exercise-induced laryngeal obstruction is an important cause of exertional dyspnoea. The diagnosis rests on visual judgement of relative changes of the laryngeal inlet during continuous laryngoscopy exercise (CLE) tests, but we lack objective measures that reflect functional consequences. We aimed to investigate repeatability and normal values of translaryngeal airway resistance measured at maximal intensity exercise. Methods: 31 healthy nonsmokers without exercise-related breathing problems were recruited. Participants performed two CLE tests with verified positioning of two pressure sensors, one at the tip of the epiglottis (supraglottic) and one by the fifth tracheal ring (subglottic). Airway pressure and flow data were continuously collected breath-by-breath and used to calculate translaryngeal resistance at peak exercise. Laryngeal obstruction was assessed according to a standardised CLE score system. Results: Data from 26 participants (16 females) with two successful tests and equal CLE scores on both test sessions were included in the translaryngeal resistance repeatability analyses. The coefficient of repeatability (CR) was 0.62 cmH2O·L-1·s-1, corresponding to a CR% of 21%. Mean±sd translaryngeal airway resistance (cmH2O·L-1·s-1) in participants with no laryngeal obstruction (n=15) was 2.88±0.50 in females and 2.18±0.50 in males. Higher CLE scores correlated with higher translaryngeal resistance in females (r=0.81, p<0.001). Conclusions: This study establishes translaryngeal airway resistance obtained during exercise as a reliable parameter in respiratory medicine, opening the door for more informed treatment decisions and future research on the role of the larynx in health and disease.

Exercise-induced Laryngeal Obstruction: Protocol for a Randomized Controlled Treatment Trial.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high-intensity exercise. Empirical data suggest that EILO consists of different subtypes, possibly requiring different therapeutic approaches. Currently applied treatments do not rest on randomized controlled trials, and international guidelines based on good evidence can therefore not be established. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO. METHODS AND ANALYSIS: Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four non-invasive treatment arms, based on promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the non-invasive approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimally invasive laser supraglottoplasty or (G) no surgery. Power calculations are based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions. ETHICS AND DISSEMINATION: The study will assess approaches to EILO treatments that despite widespread use, are insufficiently tested in structured, verifiable, randomized, controlled studies, and is therefore considered ethically sound. The study will provide knowledge listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5-7% of young people. Dissemination will occur in peer-reviewed journals, at relevant media platforms and conferences, and by engaging with patient organizations and the healthcare bureaucracy.

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

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

Tailoring NIV by dynamic laryngoscopy in a child with spinal muscular atrophy type I.

Dynamic laryngoscopy during noninvasive (NIV) respiratory therapy is feasible and may facilitate optimal and individualized treatment in patients with chronic respiratory failure, also in children.