Alveolar Hypoventilation Research Articles

Syndrome thoracique aigu chez les patients drépanocytaires adultes

Sickle cell disease is a frequent genetic condition, due to a mutation of the β-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/β0-thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry.

The Need for Titration With Polysomnography of Noninvasive Positive Pressure Ventilation in a Patient With Hypoventilation Syndrome With Kyphoscoliosis

Attended noninvasive positive airway pressure (PAP) with polysomnography (PSG) is recommended for determining the level of ventilatory support and bilevel PAP required for patients with chronic alveolar hypoventilation syndromes. We present a case of a 24-year-old male with kyphoscoliosis who presented with dyspnea. The patient was diagnosed with chronic alveolar hypoventilation and had bilevel PAP titrated by referring to tidal volume and arterial gas analysis during the day. After further titration with PSG there was stable ventilation during non-rapid eye movement sleep but unstable on entering rapid eye movement sleep.

Home mechanical ventilation in children with chronic respiratory failure: a narrative review.

Advances in perinatal and pediatric intensive care and recent advances in mechanical ventilation during the last two decades have resulted in an exponential increase in the number of children undergoing home mechanical ventilation (HMV) treatment. Although its efficacy in chronic respiratory failure is well established, HMV in children is more complex than that in adults, and there are more considerations. This review outlines clinical considerations for HMV in children. The goal of HMV in children is not only to correct alveolar hypoventilation but also to maximize development as much as possible. The modes of ventilation and ventilator settings, including ventilation masks, tubing, circuits, humidification, and ventilator parameters, should be tailored to the patient's individual characteristics. To ensure effective HMV, education for the parent and caregiver is important. HMV continues to change the scope of treatment for chronic respiratory failure in children in that it decreases respiratory morbidity and prolongs life spans. Further studies on this topic with larger scale and systemic approach are required to ensure the better outcomes in this population.

0526 Utility of polysomnography in tracheostomy decannulation process in children

Abstract Introduction Different approaches have been used to assess decannulation readiness including clinical observation with gradual tracheostomy downsizing, capping, and microlaryngoscopy and bronchoscopy. Polysomnograms with tracheostomy capping are being used at some centers prior to decannulation. We have previously shown that polysomnography is an important additional tool to predict successful decannulation. However, this study was based on a relatively small number of children. Thus the aim of this study is to review the polysomnographic features that predict decannulation outcomes in a large cohort of children with various conditions. Methods A retrospective chart review of polysomnography and medical records was performed for children 0-18 years of age preparing for tracheostomy decannulation from Feb. 2005 to June 2019 at Cincinnati Children’s Hospital Medical Center. Subjects with less than four hours of sleep time were excluded from the study. Results A total of 128 subjects were included in the study with 74 in the successful decannulation group (SD), 48 in the no decannulation group (ND) and 6 in the unsuccessful decannulation group. Underlying diagnosis included history of prematurity 41 (32%), genetic disorders 39 (30.5%), neurological disorders 17 (13.3%), airway abnormalities 108 (84.4%), and cardiac disease 24 (18.8%). Average age at the time of tracheostomy was 1.8±3.4 years and at decannulation was 5.7±3.6 years in the SD group. Favorable microlaryngoscopy/bronchoscopy (MLB) was significantly higher in SD group 73.8% vs. ND group 26.2% (p&amp;lt;0.001). Comparing polysomnographic respiratory sleep parameters showed significant differences between ND and SD groups for apnea hypopnea index (AHI)&amp;gt;10/h (88% [ND] vs. 12% [SD]; p&amp;lt;0.001) and obstructive apnea hypopnea index (OAHI)&amp;gt; 5/h (75.6% [ND] vs. 24.4% [SD]; p&amp;lt;0.001). Alveolar hypoventilation (CO2&amp;gt;50 for &amp;gt;25% of TST) was also significantly higher in the ND group (70.6%) vs. SD group (29.4%) (p&amp;lt;0.009). Conclusion In our large cohort of children undergoing decannulation, there were several differences in polysomnographic characteristics including AHI, obstructive AHI and CO2 parameters between those who were and were not successfully decannulated. In addition to unfavorable findings on airway evaluation, children who did not undergo decannulation were more likely to have moderate to severe degree of sleep disordered breathing and alveolar hypoventilation. Support (If Any) This study was supported by Cincinnati Children’s Hospital Research Fund.

Assessment of pulmonary function tests among patients with hypothyroidism

Background: The respiratory system involvement in hypothyroidism varies from mild dyspnea to a more severe respiratory failure. This has been reported as reduction in expiratory and inspiratory muscle strength, alveolar hypoventilation along with reduction of hypoxic and hypercapnic ventilatory drives and decreased maximal breathing capacity and decreased diffusion capacity among hypothyroid patients. Material &amp; Methods: The present prospective study was conducted at department of respiratory medicine of our tertiary care hospital. In present study, we enrolled 50 study participants from outdoor and from ward by simple random sampling. Clearance from Institutional Ethics Committee was taken before start of study. Written informed consent was taken from each study participant Results In the present study, majority of patients showed obstructive pattern i.e. 30% which was followed by mixed pattern among 22% patients and 18% of patients showed restrictive pattern. 30% of patients showed normal respiratory pattern on pulmonary function test. On the basis of the Spirometry examination finding among case group, the mean value of FEV1 (L) was 1.38±0.68, the man value of FVC(L) was 2.24±0.71. on assessment the mean value of FEV1/FVC proportion (postbronchodilator) was 61.6 ±11.3.

Evaluation of Clinical and Instrumental Results of Lung Examination in Patients with Diabetes Mellitus, Coronary Artery Disease, and Obesity

BACKGROUND: There are a large number of works devoted to the study of the state of the bronchopulmonary system in diabetes mellitus in the literature in the last 20 years. However, these studies are often conflicting. Some researchers identify a deterioration in the function of external respiration and a connection with metabolic changes and complications of the disease, others associate it with vascular pathology. There are a number of reports of increased pulmonary ventilation in diabetes.&#x0D; AIM: To assess the structural and functional state of the lungs in patients with diabetes mellitus and in combination with coronary heart disease and obesity.&#x0D; METHODS: 395 patients with type 1 and type 2 diabetes mellitus were under observation. The diagnosis of diabetes mellitus was verified in accordance with International Programs and was based on WHO criteria. The glycemic level of patients was determined using a One Touch® basic glucometer (Johnson&amp;Johnson, USA). The degree of carbohydrate metabolism compensation was assessed by the level of glycated hemoglobin (HbA1c), determined using a laboratory analyzer DCA-2000 MT (BAYER, Germany). The concentration of C-peptide in the blood serum was determined by the method of immunoluminometric analysis "Immunotech" (Czech Republic). Caro and HOMA-IR indices were calculated to identify and assess the insulin resistance (IR). The indices of hormone metabolism were determined by ELISA using DSL kits (USA) with subsequent measurement of optical density on a Spectra Classic reader from Tecan (Austria): corticotropic hormone (CTG), adrenaline, noradrenaline, cortisol, free hydrocortisone; 17-ketosteroids, 17-oxycorticosteroids, glucogone, insulin, somatotropic hormone (STH); thyroid stimulating hormone (TSH); thyroxine (T4); thyroxine (T3).&#x0D; Instrumental-functional and radiation research methods:&#x0D; X-ray methods for lungs examining, computer spirography, fibrobronchoscopy of the bronchi was performed in all patients. Morphological changes were assessed using histological and morphometric methods.&#x0D; &#x0D; RESULTS: Pathogenetic mechanisms of the bronchopulmonary system disorders in patients with type 1 diabetes mellitus are associated with a decrease in the function of external respiration due to the volumetric air flow rates of the predominantly central airways and an increase in bronchial resistance. Alveolar hypoventilation of a restrictive type with impaired diffusion of gases through the alveolar-capillary membrane was detected in patients with type 2 diabetes mellitus. Restrictive and obstructive type disorders with impaired ventilation-perfusion ratios and pulmonary blood flow are formed in patients with type 2 diabetes mellitus combined with coronary artery disease and obesity.&#x0D; &#x0D; CONCLUSION:&#x0D; &#x0D; A decrease in the function of external respiration due to the central respiratory tract and an increase in bronchial resistance were noted in 38.4% of patients with type 1 diabetes mellitus. Restrictive alveolar hypoventilation was registered in 23.3% of patients with type 2 diabetes mellitus, catarrhal endobronchitis – in 21.31% of patients with type 2 diabetes mellitus.&#x0D; Damage and fibrosis of the alveolar tissue, damage to the endothelium and disorganization of the connective tissue of the lungs were characteristic of microscopic examination of the ultrastructure of the lungs in patients with diabetes mellitus.&#x0D;

Clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome combined with alveolar hypoventilation

Objective: To evaluate the clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with alveolar hypoventilation. Methods: This retrospective study included patients who were diagnosed as OSAHS by polysomnography (PSG) and underwent daytime awake transcutaneous carbon dioxide (PtcCO2) monitoring from November 2019 to February 2021 at the Sleep Center of the Second Affiliated Hospital of Soochow University. A total of 177 patients were enrolled in the analysis, including 167 males and 10 females, aged (40±8) years old. Patients with daytime awake PtcCO2>45 mmHg (1 mmHg=0.133 kPa) were diagnosed as daytime alveolar hypoventilation, with which participants were divided into the daytime alveolar hypoventilation group and non-daytime alveolar hypoventilation group. Body mass index (BMI) cut-off value predicting daytime alveolar hypoventilation was calculated and the patients were divided into the high BMI group and low BMI group. The continuous nocturnal PtcCO2 data was available for a subset of 128 patients, and the patients were divided into two groups according the daytime alveolar hypoventilation or not. Across-group differences were compared, respectively. Results: Compared with the non-daytime alveolar hypoventilation group (n=125), the BMI [27.57 (26.55, 30.33) vs 26.60 (25.06, 28.09) kg/m2], Epworth sleepiness score(ESS) score [9.50 (6.25, 12.00) vs 7.00 (4.00, 10.75)], higher oxygen desaturation index (ODI) [38.00 (15.23, 64.93) vs 26.80 (11.30, 44.30) events/h] and percentage of total time with oxygen saturation level<90% (TS90%) [11.24% (1.88%, 32.44%) vs 4.35% (0.72%, 9.87%)] of the daytime alveolar hypoventilation group(n=52) were significantly higher (P<0.05), and lowest arterial oxygen saturation (LSaO2) [74.50% (60.25%, 82.00%) vs 79.00% (73.00%, 84.50%)], mean arterial oxygen saturation (MSaO2) [94.00% (91.00%, 95.00%) vs 95.00% (94.00%, 96.00%)] were significantly lower (P<0.05). The BMI cut-off value for predicting daytime alveolar hypoventilation was 27.04 kg/m2. Of the 177 enrolled patients, 90 were in the high BMI group and 87 were in low group. Compared with the low BMI group, the proportion of daytime sleepiness, the ESS score, the prevalence of hypertension, AHI and daytime awake PtcCO2 in the high BMI group were significantly higher (P<0.05). Among the subset of 128 patients with nocturnal PtcCO2 data available, the BMI, daytime PtcCO2 level, the nocturnal CO2 level and the prevalence of sleep related alveolar hypoventilation in the daytime alveolar hypoventilation group (n=40) were significantly higher than those in the non-daytime alveolar hypoventilation group (n=88) (P<0.05). Conclusions: The OSAHS patients with alveolar hypoventilation have higher BMI and more severe nocturnal hypoxia. OSAHS patients with BMI>27.04 kg/m2 are more likely to develop sleep related alveolar hypoventilation disorder.

Rare cause of neonatal apnea from congenital central hypoventilation syndrome

BackgroundCongenital central hypoventilation syndrome (CCHS) is a rare condition caused by mutations in the Paired-Like Homeobox 2B (PHOX2B) gene. It causes alveolar hypoventilation and autonomic dysregulation. This report aimed to raise awareness of this rare cause of neonatal apnea and hypoventilation as well as described the diagnostic work up to confirm the diagnosis in resource-limited setting where polysomnography for neonate is unavailable.Case presentationA late preterm female newborn born from a non-consanguineous primigravida 31-year-old mother had desaturation soon after birth followed by apnea and bradycardia. After becoming clinically stable, she still had extubation failure from apnea without hypercapnic ventilatory response which worsened during non-rapid eye movement (NREM) sleep. After exclusion of other etiologies, we suspected congenital central hypoventilation syndrome and sent genetic testing. The result showed a PHOX2B gene mutation which confirmed the diagnosis of CCHS. We gave the patient’s caregivers multidisciplinary home respiratory care training including tracheostomy care, basic life support, and simulation training for respiratory problem solving. Then, the patient was discharged and scheduled for follow-up surveillance for associated conditions.ConclusionDiagnosis of CCHS in neonates includes the main clue of the absence ofhypercapnic ventilatory response which worsens during non-rapid eye movement(NREM) sleep after exclusion of other causes. Molecular testing for PHOX2Bgene mutation was used to confirm the diagnosis.

Enchanced preoperative rehabilitation as part of the complex perioperative rehabilitation of patients with super-obesity and obstructive sleep apnea syndrome (clinical outlook)

Obesity is a global social and economic problem. The bariatric surgery is a most effective treatment for obesity. The presented clinical case demonstrates the usage of principles of enchanced perioperative rehabilitation for the preoperative preparation of a patient with super obesity and with severe obstructive sleep apnea and alveolar hypoventilation syndrome.A 54-year-old patient was hospitalized with complaints of obesity, impossibility of persistent weight loss conservatively, severe daytime sleepiness, frequent nocturnal awakenings (up to 8 times per night). The patient’s weight was 230 kg with a height of 157 cm (BMI 93.5 kg / m2). The examination revealed a syndrome of sleep apnea of mixed genesis of extremely severe degree, chronic night hypoxemia of an extremely severe degree. Preoperative preparation was performed in accordance with the program of enchanced perioperative rehabilitation. The duration of preoperative preparation was 19 days; weight loss — 40 kg (%WL -17,4), compensation of comorbidities was achieved as well. After that the patient underwent a laparoscopic sleeve gastrectomy. There were no complications in the postoperative period. Length of postoperative hospital stay was 6 days. At follow-up examination one year after surgery, body weight dropped from 230 to 153 kg (% WL-33.5), a significant improvement of the quality of life was achieved.The enchanced perioperative rehabilitation program can be successfully used as an effective method for preoperartive preparation of the patients with morbid obesity in combination with severe obstructive sleep apnea syndrome.and obesity hypoventilation. It can be a reasonable alternative to the standard program with preoperative intragastric balloon treatment. The use of this technique allows to increase the effectiveness of treatment of these high-risk patients, as well as to reduce the risk of perioperative complications.

Hypoxemia: from pathophysiology to diagnosis

Hypoxemia is defined as a decreased oxygen partial pressure in arterial blood. This frequent clinical phenomenon can lead to tissue hypoxia and requires a prompt diagnostic approach to guide its management. Five pathophysiological mechanisms should be assessed in the presence of hypoxemia: alveolar hypoventilation, ventilation/perfusion mismatches, diffusion disorders, true shunts and a decrease in the partial pressure of inspired oxygen. In this article, we synthesize the main etiologies of hypoxemia based on respiratory pathophysiology and suggest a diagnostic approach for its evaluation.

Chapter 4 - Developmental disorders affecting the respiratory system: CCHS and ROHHAD

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) and Congenital Central Hypoventilation Syndrome (CCHS) are ultra-rare distinct clinical disorders with overlapping symptoms including altered respiratory control and autonomic regulation. Although both disorders have been considered for decades to be on the same spectrum with necessity of artificial ventilation as life-support, recent acquisition of specific knowledge concerning the genetic basis of CCHS coupled with an elusive etiology for ROHHAD have definitely established that the two disorders are different. CCHS is an autosomal dominant neurocristopathy characterized by alveolar hypoventilation resulting in hypoxemia/hypercarbia and features of autonomic nervous system dysregulation (ANSD), with presentation typically in the newborn period. It is caused by paired-like homeobox 2B (PHOX2B) variants, with known genotype-phenotype correlation but pathogenic mechanism(s) are yet unknown. ROHHAD is characterized by rapid weight gain, followed by hypothalamic dysfunction, then hypoventilation followed by ANSD, in seemingly normal children ages 1.5-7 years. Postmortem neuroanatomical studies, thorough clinical characterization, pathophysiological assessment, and extensive genetic inquiry have failed to identify a cause attributable to a traditional genetic basis, somatic mosaicism, epigenetic mechanism, environmental trigger, or other. To find the key to the ROHHAD pathogenesis and to improve its clinical management, in the present chapter, we have carefully compared CCHS and ROHHAD.

P10‐17: Idiopathic central alveolar hypoventilation without respiratory failure that required differentiation from obstructive sleep apnea

P10‐17: Idiopathic central alveolar hypoventilation without respiratory failure that required differentiation from obstructive sleep apnea

Impairment of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a serious complication of severe systemic or local pulmonary inflammation, such as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ARDS is characterised by diffuse alveolar damage that leads to protein-rich pulmonary oedema, local alveolar hypoventilation and atelectasis. Inadequate perfusion of these areas is the main cause of hypoxaemia in ARDS. High perfusion in relation to ventilation (V/Q<1) and shunting (V/Q=0) is not only caused by impaired hypoxic pulmonary vasoconstriction but also redistribution of perfusion from obstructed lung vessels. Rebalancing the pulmonary vascular tone is a therapeutic challenge. Previous clinical trials on inhaled vasodilators (nitric oxide and prostacyclin) to enhance perfusion to high V/Q areas showed beneficial effects on hypoxaemia but not on mortality. However, specific patient populations with pulmonary hypertension may profit from treatment with inhaled vasodilators. Novel treatment targets to decrease perfusion in low V/Q areas include epoxyeicosatrienoic acids and specific leukotriene receptors. Still, lung protective ventilation and prone positioning are the best available standard of care. This review focuses on disturbed perfusion in ARDS and aims to provide basic scientists and clinicians with an overview of the vascular alterations and mechanisms of V/Q mismatch, current therapeutic strategies, and experimental approaches.

Defining obesity hypoventilation syndrome.

With increasing prevalence of obesity, the substantial contribution of obesity hypoventilation syndrome (OHS) to morbidity and mortality is likely to increase. It is therefore crucial that the condition has a clear definition to allow timely identification of patients. OHS was first described as “Pickwickian syndrome” in the 1950s; in subsequent decades, case reports did not clearly delineate between patients suffering from OHS and those suffering from obstructive sleep apnoea. In 1999, the American Academy of Sleep Medicine published a guideline that delineated the cause of daytime hypercapnia as either predominantly upper airway or predominantly hypoventilation. This was the first formal definition of OHS as the presence of daytime alveolar hypoventilation (arterial carbon dioxide tension >45 mmHg) in patients with body mass index >30 kg·m−2 in the absence of other causes of hypoventilation. This definition is reflected in the most recent guidelines published on OHS. Recent developments in defining OHS include proposed classification systems of severity and demonstrating the value of using serum bicarbonate to exclude OHS in patients with a low index of suspicion.Educational aimsTo provide an overview of the historical basis of the definition of obesity hypoventilation syndrome.To explain the rationale for the current definition of obesity hypoventilation syndrome.To demonstrate areas that need further investigation in defining obesity hypoventilation syndrome.

TRAF2 Is a Novel Ubiquitin E3 Ligase for the Na,K-ATPase β-Subunit That Drives Alveolar Epithelial Dysfunction in Hypercapnia.

Several acute and chronic lung diseases are associated with alveolar hypoventilation leading to accumulation of CO2 (hypercapnia). The β-subunit of the Na,K-ATPase plays a pivotal role in maintaining epithelial integrity by functioning as a cell adhesion molecule and regulating cell surface stability of the catalytic α-subunit of the transporter, thereby, maintaining optimal alveolar fluid balance. Here, we identified the E3 ubiquitin ligase for the Na,K-ATPase β-subunit, which promoted polyubiquitination, subsequent endocytosis and proteasomal degradation of the protein upon exposure of alveolar epithelial cells to elevated CO2 levels, thus impairing alveolar integrity. Ubiquitination of the Na,K-ATPase β-subunit required lysine 5 and 7 and mutating these residues (but not other lysines) prevented trafficking of Na,K-ATPase from the plasma membrane and stabilized the protein upon hypercapnia. Furthermore, ubiquitination of the Na,K-ATPase β-subunit was dependent on prior phosphorylation at serine 11 by protein kinase C (PKC)-ζ. Using a protein microarray, we identified the tumor necrosis factor receptor-associated factor 2 (TRAF2) as the E3 ligase driving ubiquitination of the Na,K-ATPase β-subunit upon hypercapnia. Of note, prevention of Na,K-ATPase β-subunit ubiquitination was necessary and sufficient to restore the formation of cell-cell junctions under hypercapnic conditions. These results suggest that a hypercapnic environment in the lung may lead to persistent epithelial dysfunction in affected patients. As such, the identification of the E3 ligase for the Na,K-ATPase may provide a novel therapeutic target, to be employed in patients with acute or chronic hypercapnic respiratory failure, aiming to restore alveolar epithelial integrity.

554 Utilization of Pediatric Sleep Questionnaire to Screen for Obstructive Sleep Apnea in a Difficult-to-treat Asthma Cohort

Abstract Introduction Early detection and management of obstructive sleep apnea(OSA) could improve asthma control in children with difficult-to-treat(DTT) asthma. The purpose of this study was to assess the effectiveness of the pediatric sleep questionnaire(PSQ) to screen for OSA in children with DTT asthma, and to compare clinical characteristics between those with positive and negative PSQ scores. Methods A prospective study of 81 children with DTT asthma was completed from 2015–2017. The PSQ, Epworth sleepiness scale(ESS), Pediatric Quality of Life(PQL), and the academic performance questionnaires(APQ) were administered during clinic visits. Polysomnography(PSG) was recommended for PSQ score&amp;gt;0.33. Medical records were reviewed for asthma clinical characteristics. The cohort was separated into positive(PSQ&amp;gt;0.33) and negative PSQ score(PSQ≤0.33) groups for analysis. Results The mean age of the cohort was 11.3±4.5 years and the mean body mass index was 22±7.6 kg/m2. Sixty-two percent were male and 68% were African-American. Forty-nine(53%) subjects had positive PSQ (0.5[0.4 – 0.7]). The positive group had higher ESS score (10.5[8 – 13] vs. 6[2 – 8], p&amp;lt;0.0001) and lower total PQL score (58.7[47.8–72.8] vs. 79.4[70.7 – 87], p&amp;lt;0.0001) than the negative group. There was no difference between APQ scores(p=0.07). The positive group had lower asthma control test(ACT) scores than the negative group (17.5[15 – 20.5] vs. 21[19 – 22], p&amp;lt;0.0001). Furthermore, the positive group was more likely to have gastroesophageal reflux (OR: 3.97, 95%CI: 1.7 to 9.1, p=0.0018). Twenty-nine(59%) subjects in the positive group had subsequent PSG, and 17(58.6%) subjects were diagnosed with OSA (14 mild OSA, 1 moderate OSA, 2 severe OSA). The mean obstructive index in the positive group was 3±5.5 events/hour. There was 1 subject with central apnea and alveolar hypoventilation. Of the 17 subjects with OSA, all received treatment with nasal steroids, 3 were treated with non-invasive positive pressure ventilation, and 4 had surgical intervention. Conclusion Children with DTT asthma who have positive PSQ have higher degree of daytime sleepiness, lower quality of life and worse asthma control. The positive group was more likely to have GERD, which may suggest a relationship between nighttime asthma symptoms and OSA. Further studies are needed to evaluate the effects of OSA treatment on asthma control. Support (if any):

848 Refractory Hypoventilation in Congenital Central Hypoventilation Syndrome: A Case for Average Volume-Assured Pressure Support

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a rare cause of alveolar hypoventilation in children resulting in lifelong ventilatory support. In older children requiring nocturnal support alone, the use of diaphragmatic pacing in conjunction with or independent of non-invasive ventilatory (NIV) support has been demonstrated to improve quality of life. We present a case of refractory hypoventilation despite escalation of NIV. Report of case(s) 20-year-old female with Hirschsprung’s disease and CCHS (20/26 polyalanine repeats) with history of invasive ventilation via tracheostomy who underwent bilateral diaphragmatic phrenic nerve stimulator placement at 13 years-of-age with subsequent tracheostomy decannulation. Diaphragmatic pacing was discontinued three years later in the setting of pneumonia and patient discomfort because of receiver positioning. At that time, she had improved subjective sleep quality and adequate ventilatory support on bi-level positive airway pressure (PAP) despite discontinuation of diaphragmatic pacing. Titration of bi-level PAP was done via polysomnogram four years later demonstrating nocturnal hypoventilation with transcutaneous CO2 values greater than 50 mmHg for 80% of the study and an oxygen nadir of 87% despite titration of inspiratory pressure and respiratory rate to maximize ventilatory assistance. The patient was subsequently admitted to the intensive care unit for transition to non-invasive average volume-assured pressure support (AVAPS) mode. Ventilation improved with nocturnal pCO2 values via capillary blood gas of 31 mmHg and 45 mmHg at 2 am and 6 am respectively. The patient was discharged on AVAPS therapy while undergoing evaluation to resume diaphragmatic pacing via cervical phrenic nerve stimulators for improved comfort. Conclusion Several ventilatory strategies may be employed in the care of patients with CCHS, with individualization of support based on phenotype, comorbidities, and patient and family preference. This case highlights the unique challenges of adequately ventilating patients as they age. The use of NIV via an AVAPS mode in patients with CCHS has been infrequently reported in the literature, though is promising in reported efficacy with regards to ensured ventilation. This, in conjunction with diaphragmatic pacing, may allow patients to achieve appropriate ventilation while maintaining quality of life, and could be considered in patients with refractory hypoventilation despite other modes of NIV. Support (if any):

Sleep‐disordered breathing and its management in children with rare skeletal dysplasias

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

Hypercapnia in COPD Patients Undergoing Endobronchial Ultrasound under Local Anaesthesia and Analgosedation: A Prospective Controlled Study Using Continuous Transcutaneous Capnometry

Background: Flexible bronchoscopy (FB) in analgosedation causes alveolar hypoventilation and hypercapnia, the more so if patients suffer from COPD. Nonetheless, neither is capnometry part of standard monitoring nor is there evidence on how long patients should be monitored after sedation. Objectives: We investigated the impact of COPD on hypercapnia during FB with endobronchial ultrasound (EBUS) in sedation and how the periprocedural monitoring should be adapted. Methods: Two cohorts of consecutive patients – with advanced and without COPD – with the indication for FB with EBUS-guided transbronchial needle aspiration in analgosedation received continuous transcutaneous capnometry (p_tcCO₂) before, during, and for 60 min after the sedation with midazolam and alfentanil. Main Results: Forty-six patients with advanced COPD and 44 without COPD were included. The mean examination time was 26 ± 9 min. Patients with advanced COPD had a higher peak p_tcCO₂ (53.7 ± 7.1 vs. 46.8 ± 4.8 mm Hg, p < 0.001) and mean p_tcCO₂ (49.5 ± 6.8 vs. 44.0 ± 4.4 mm Hg, p < 0.001). Thirty-six percent of all patients reached the maximum hypercapnia after FB in the recovery room (8 ± 11 min). Patients with COPD needed more time to recover to normocapnia (22 ± 24 vs. 7 ± 11 min, p < 0.001). They needed a nasopharyngeal tube more often (28 vs. 11%, p < 0.001). All patients recovered from hypercapnia within 60 min after FB. No intermittent ventilation manoeuvres were needed. Conclusion: A relevant proportion of patients reached their peak-pCO₂ after the end of intervention. We recommend using capnometry at least for patients with known COPD. Flexible EBUS in analgosedation can be safely performed in patients with advanced COPD. For patients with advanced COPD, a postprocedural observation time of 60 min was sufficient.

Infectious aetiologies of severe acute chest syndrome in sickle-cell adult patients, combining conventional microbiological tests and respiratory multiplex PCR

Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.