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Background: Kennedy's disease (KD), also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, X-linked recessive neuromuscular disease caused by CAG expansions in exon 1 of the androgen receptor gene (AR). The objective of the French national diagnostic and management protocol is to provide evidence-based best practice recommendations and outline an optimised care pathway for patients with KD, based on a systematic literature review and consensus multidisciplinary observations.Results: The initial evaluation, confirmation of the diagnosis, and management should ideally take place in a tertiary referral centre for motor neuron diseases, and involve an experienced multidisciplinary team of neurologists, endocrinologists, cardiologists and allied healthcare professionals. The diagnosis should be suspected in an adult male presenting with slowly progressive lower motor neuron symptoms, typically affecting the lower limbs at onset. Bulbar involvement (dysarthria and dysphagia) is often a later manifestation of the disease. Gynecomastia is not a constant feature, but is suggestive of a suspected diagnosis, which is further supported by electromyography showing diffuse motor neuron involvement often with asymptomatic sensory changes. A suspected diagnosis is confirmed by genetic testing. The multidisciplinary assessment should ascertain extra-neurological involvement such as cardiac repolarisation abnormalities (Brugada syndrome), signs of androgen resistance, genitourinary abnormalities, endocrine and metabolic changes (glucose intolerance, hyperlipidemia). In the absence of effective disease modifying therapies, the mainstay of management is symptomatic support using rehabilitation strategies (physiotherapy and speech therapy). Nutritional evaluation by an expert dietician is essential, and enteral nutrition (gastrostomy) may be required. Respiratory management centres on the detection and treatment of bronchial obstructions, as well as screening for aspiration pneumonia (chest physiotherapy, drainage, positioning, breath stacking, mechanical insufflation-exsufflation, cough assist machnie, antibiotics). Non-invasive mechanical ventilation is seldom needed. Symptomatic pharmaceutical therapy includes pain management, endocrine and metabolic interventions. There is no evidence for androgen substitution therapy.Conclusion: The French national Kennedy's disease protocol provides management recommendations for patients with KD. In a low-incidence condition, sharing and integrating regional expertise, multidisciplinary experience and defining consensus best-practice recommendations is particularly important. Well-coordinated collaborative efforts will ultimately pave the way to the development of evidence-based international guidelines. [ABSTRACT FROM AUTHOR]

OBJECTIVES Phrenic nerve stimulation for diaphragm pacing allows patients with central respiratory paralysis to be weaned from mechanical ventilation. Two procedures are available, either intrathoracic (bilateral thoracotomy) or intradiaphragmatic (four ports laparoscopy). The present experimental work assesses the feasibility, safety and efficacy of a trans-mediastinal implantation of intradiaphragmatic phenic nerve stimulation electrodes using a flexible gastroscope through a cervical incision. METHODS We operated on nine ewes. After selective bronchial intubation, we dissected the latero-tracheal space and opened both mediastinal pleura. We then introduced a flexible gastroscope into the pleural cavities, in a sequential manner. The phrenic nerves were located and followed up to the diaphragm dome. Electrodes loaded within a long, pliable needle were introduced through the adjacent intercostal space and implanted in each hemidiaphragm, at a ‘tendinous’ location (as close as possible to the entry of the nerve in the central tendon), and at a more lateral ‘muscular’ location. Postoperatively, the animals were ventilated using bilateral phrenic nerve stimulation. After euthanasia, abdominal verification of the electrodes position was performed through a laparotomy. RESULTS The mediastinal and pleural parts of the procedure were uneventful. The insertion of electrodes was associated with transdiaphragmatic puncture and small abdominal haematomas in the first two animals studied. After a slight modification of the insertion technique, this was not observed anymore. Phrenic nerve stimulation produced efficient ventilation, with tidal volumes significantly higher when delivered at the tendinous site than at the muscular site. CONCLUSIONS The trans-mediastinal implantation of intradiaphragmatic phrenic nerve stimulation electrodes is feasible, appears reasonably safe, and allows efficient ventilation. [ABSTRACT FROM AUTHOR]

Question: Human PHOX2B mutations result in life-threatening sleep-related hypoventilation (congenital central hypoventilation syndrome, CCHS). Most patients retain ventilatory activity when awake through a respiratory-related cortical network. We hypothesised that this need to mobilise cortical resources to breathe would lead to breathing-cognition interferences during cognitive loading., Patients and Methods: Seven adult CCHS patients (five women; median age 21) performed standard neuropsychological tests (paced auditory serial addition test - calculation capacity, working memory, sustained and divided attention; trail making test - visuospatial exploration capacity, cognitive processing speed, attentional flexibility; Corsi block-tapping test - visuospatial memory, short-term memory, working memory) during unassisted breathing and under ventilatory support. Ventilatory variables and transcutaneous haemoglobin oxygen saturation were recorded. Cortical connectivity changes between unassisted breathing and ventilatory support were assessed using electroencephalographic recordings (EEG)., Results: Baseline performances were lower than expected in individuals of this age. During unassisted breathing, cognitive loading coincided with increased breathing variability, and decreases in oxygen saturation inversely correlated with an increasing number of apnoeic cycles per minute (rho -0.46, 95% CI -0.76 to -0.06, p=0.01). During ventilatory support, cognitive tasks did not disrupt breathing pattern and were not associated with decreased oxygen saturation. Ventilatory support was associated with changes in EEG cortical connectivity but not with improved test performances., Conclusions: Acute cognitive loads induce oxygen desaturation in adult CCHS patients during unassisted breathing, but not under ventilatory support. This justifies considering the use of ventilatory support during mental tasks in CCHS patients to avoid repeated episodes of hypoxia., Competing Interests: Conflict of interest: The study did not involve any conflict of interest, financial or otherwise., (Copyright ©The authors 2023.)

Question Addressed: In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health., Methods: General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered "no" to "treated for a chronic respiratory disease" ("respiratory healthy"), and 152 answered "yes" ("respiratory disease"). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family + ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . RESULTS: Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). "Air hunger" was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family + (OR 1.85, 95% CI 1.16-2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73-7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25-0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences., Answer to the Question: Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions., Competing Interests: Conflict of interest: L. Serresse has nothing to disclose. Conflict of interest: N. Simon-Tillaux has nothing to disclose. Conflict of interest: M. Decavèle has nothing to disclose. Conflict of interest: F. Gay has nothing to disclose. Conflict of interest: N. Nion has nothing to disclose. Conflict of interest: S. Lavault has nothing to disclose. Conflict of interest: A. Guerder has nothing to disclose. Conflict of interest: A. Châtelet is an employee of the IFOP polling institute. Conflict of interest: F. Dabi is an employee of the IFOP polling institute. Conflict of interest: A. Demoule reports grants, personal fees and non-financial support from Philips, Respinor and Lungpacer, personal fees from Baxter, Getinge, Lowenstein and Gilead, personal fees and non-financial support from Fisher & Paykel, grants from French Ministry of Health, outside the submitted work. Conflict of interest: C. Morélot-Panzini reports personal fees for lectures and board membership from AstraZeneca, GSK, SOS Oxygène, ADEP, ISIS, Resmed, Chiesi, Menarini, Vivisol, Air Liquide, Lowenstein, Fisher & Paykel, outside the submitted work. Conflict of interest: C. Moricot has nothing to disclose. Conflict of interest: T. Similowski reports personal fees from AstraZeneca France, Boehringer Ingelheim France, TEVA France, Chiesi France, Lungpacer Inc. and ADEP Assistance, personal fees and non-financial support from Novartis France, grants from Air Liquide Medical Systems, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Dynamic hyperinflation is observed during exercise in 60% of patients with clinically stable pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), intensifying exertional dyspnoea. The impact of dynamic changes in respiratory mechanics during exercise on qualitative dimensions of dyspnoea in these patients has not been evaluated.26 patients (PAH n=17; CTEPH n=9) performed an incremental symptom-limited cycle exercise test. Minute ventilation ( V ' E ), breathing pattern, operating lung volumes and dyspnoea intensity were assessed throughout exercise. Dyspnoea quality was serially assessed during exercise using a three-item questionnaire (dyspnoea descriptors). The inflection point of tidal volume ( V T ) relative to V ' E was determined for each incremental test. Changes in inspiratory capacity during exercise defined two groups of patients: hyperinflators (65%) and non-hyperinflators (35%). Multidimensional characterisation of dyspnoea was performed after exercise using the Multidimensional Dyspnea Profile.In hyperinflators, inspiratory capacity decreased progressively throughout exercise by 0.36 L, while remaining stable in non-hyperinflators. The "work/effort" descriptor was most frequently selected throughout exercise in both types of patients (65% of all responses). At the V T / V ' E inflection, work/effort plateaued while "unsatisfied inspiration" descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the V T / V ' E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the V T / V ' E inflection may have important implications for symptom management in patients with pulmonary hypertension., Competing Interests: Conflict of interest: A. Boucly reports personal fees and non-financial support from Actelion Pharmaceuticals and Merck, non-financial support from Bayer HealthCare and GlaxoSmithKline, outside the submitted work. Conflict of interest: C. Morélot-Panzini reports personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Novartis, Philips, ADEP and SOS Oxygene, outside the submitted work. Conflict of interest: G. Garcia has nothing to disclose. Conflict of interest: J. Weatherald has nothing to disclose. Conflict of interest: X. Jaïs reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer HealthCare, GlaxoSmithKline and MSD, outside the submitted work. Conflict of interest: L. Savale reports grants and personal fees from Actelion Pharmaceuticals and Bayer HealthCare, personal fees from GlaxoSmithKline and Merck, outside the submitted work. Conflict of interest: D. Montani reports grants and personal fees from Actelion Pharmaceuticals and Bayer HealthCare, personal fees from GlaxoSmithKline, Novartis, Pfizer and BMS, outside the submitted work. Conflict of interest: M. Humbert has relationships with drug companies including Actelion, Bayer, GSK, Merck and United Therapeutics; in addition to being investigator in trials involving these companies, relationships include consultancy services and membership of scientific advisory boards. Conflict of interest: T. Similowski reports personal fees from AstraZeneca, Boehringer Ingelheim France, GSK, Lungpacer Inc., TEVA, Chiesi and Invacare, personal fees and non-financial support from Novartis, outside the submitted work. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and GlaxoSmithKline, personal fees from Acceleron Pharmaceuticals, Arena Pharmaceuticals and Gossamer Bio, grants and personal fees from Bayer HealthCare and Merck, outside the submitted work. Conflict of interest: P. Laveneziana reports personal fees from Novartis France and Boehringer France, outside the submitted work., (Copyright ©ERS 2020.)

Background: The purpose of this study was to describe the sleep structure (especially slow wave sleep) in adults with congenital central hypoventilation syndrome (CCHS), a rare genetic disease due to mutations in the PHOX2B gene. Fourteen patients aged 23 (19.0; 24.8) years old (median [1 rst -3rd quartiles]) with CCHS underwent a sleep interview and night-time attended polysomnography with their ventilatory support. Their sleep variables were compared to those collected in 15 healthy control subjects matched for age, sex and body mass index., Results: The latency to N3 sleep was shorter in patients (26.3 min [24.0; 30.1]) than in controls (49.5 min [34.3; 66.9]; P = 0.005), and sleep onset latency tended to be shorter in patients (14.0 min [7.0; 20.5]) than in controls (33.0 min [18.0; 49.0]; P = 0.052). Total sleep time, sleep stage percentages, sleep fragmentation as well as respiratory and movement index were within normal ranges and not different between groups., Conclusions: Normal sleep in adult patients with CCHS and adequate ventilator support indicates that the PHOX2 gene mutations do not affect brain sleep networks. Consequently, any complaint of disrupted sleep should prompt clinicians to look for the usual causes of sleep disorders, primarily inadequate mechanical ventilation. Shorter N3 latency may indicate a higher need for slow wave sleep, to compensate for the abnormal respiratory-related cortical activity during awake quiet breathing observed in patients with CCH.