A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options.

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.

The First Korean Case with Cardiac, Facial, and Digital Anomalies with Developmental Delay Caused by De Novo TRAF7 p.Arg655Gln Variant.

TRAF7-related disorders represent some of the rarest inherited disorders, exhibiting clinical features that overlap with cardiac, facial, and digital anomalies with developmental delay (CAFDADD) syndrome, as well as blepharophimosis-mental retardation syndrome (BMRS). A 36-year-old male, presenting with total blindness, blepharophimosis, and intellectual disability, was admitted for the assessment of resting dyspnea several months previously. He had a history of being diagnosed with obstructive sleep apnea (OSA). Transesophageal and transthoracic echocardiography unveiled right ventricular dilatation without significant pulmonary hypertension, bicuspid aortic valve with aortic root aneurysm, and aortic regurgitation in the proband. Sanger sequencing identified a de novo TRAF7 variant (c.1964G>A; p.Arg655Gln). Subsequently, aortic root replacement using the Bentall procedure was performed. However, despite the surgery, he continued to experience dyspnea. Upon re-evaluating OSA with polysomnography, it was discovered that continuous positive airway pressure support alleviated his symptoms. The underlying cause of his symptoms was attributed to OSA, likely exacerbated by the vertebral anomaly and short neck associated with CAFDADD syndrome. Clinicians should be attentive to the symptoms associated with OSA as it is a potentially serious medical condition in patients with TRAF7 variants.

Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea.

BACKGROUND: In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. METHODS AND RESULTS: We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All-cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5-year follow-up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90-2.02). At 5-year follow-up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78-1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60-5.54]). CONCLUSIONS: Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects.

BACKGROUND: Desmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients. METHODS: Muscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA. RESULTS: Our findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT-qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01). CONCLUSIONS: Our study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.

Superiorly Based Posterior Pharyngeal Flaps: Using A Care Pathway to Optimize Speech and Airway Outcomes.

BACKGROUND: Pharyngeal flap (PF) surgery is effective at improving velopharyngeal sufficiency, but historical literature shows a concerning prevalence rate of obstructive sleep apnea (OSA), reported as high as 20%. Our institution has developed a protocol to minimize risk of postoperative obstructive complications and increase safety of PF surgery. We hypothesize that (1) preoperative staged removal of significant adenotonsillar tissue along with (2) multiview videofluoroscopy to guide patient-specific surgical approach via appropriately sized PFs can result in excellent speech outcomes while limiting occurrence of OSA. METHODS: This was a retrospective chart review of all patients with velopharyngeal insufficiency (VPI) (aged 2-20 years) seen at the University of Rochester from 2015 to 2022 undergoing PF surgery to correct VPI. Nasopharyngoscopy was used for surgical planning and airway evaluation. Patients with tonsillar and adenoid hypertrophy underwent staged adenotonsillectomy at least 2 months before PF. Multiview videofluoroscopy was used to identify anatomic causes of VPI and to determine PF width. Patients underwent polysomnography and speech evaluation before and at least 6 months after PF surgery. RESULTS: Forty-one children aged 8.5 ± 4.1 years (range, 4 to 18 years) who underwent posterior PF surgery for VPI were identified. This included 10 patients with 22q11.2 deletion and 4 patients with Pierre Robin sequence. Thirty-nine patients had both pre- and postoperative speech data and underwent both a pre- and postoperative sleep study. Polysomnography showed no significant difference in obstructive apnea-hypopnea index after posterior PF surgery (obstructive apnea-hypopnea index preop, 1.3 ± 1.2 events per hour; postop, 1.7 ± 2.1 events per hour; P = 0.111). Significant improvements in speech outcome were seen in patients who underwent PF (modified Pittsburgh score preop, 11.52 ± 1.37; postop, 1.09 ± 2.35; P < 0.05). CONCLUSIONS: Use of preoperative staged adenotonsillectomy as well as patient-specific PF dimensions results in effective resolution of VPI and a low risk of OSA.

Sickle Cell Disease Phenotypes and Obstructive Sleep Apnea; Are They Related?

OBJECTIVE: This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD). MATERIALS AND METHODS: This prospective cross-sectional study was conducted in the Children's Hospital at King Fahad MedicalCity, in Riyadhwhere childrenwere recruited fromthe pediatric hematology clinic and pediatric sleepmedicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study. RESULTS: Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their body mass index z score was -1.45 (-2.195, -1.45). The evidence of obstructive sleep apnea (OSA) was more prominent in the Benin phenotype (66.7%) in comparison to those of the Arab-Indian (35.2%) phenotype ( p = 0.006). Additionally, 56.7% of Benin had moderate to severe OSA whereas Arab-Indian had 18% with a ( p = 0.0003). Controlling for other factors, the odds ratio (confidence interval) of having OSA in Benin phenotype was 4.68 (1.42-15.38) times higher as compared to Arab-Indian phenotype. CONCLUSION: The risk of having OSA as well as the severity of OSA is higher in Benin phenotype as compared to Arab-Indian phenotype which indicates the presence of potential OSA risk factors other than the SCD itself.

Effects of sleep-disordered breathing on serum lipid levels in children:a case control study.

BACKGROUND: Sleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese. METHODS: This was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays. RESULTS: A total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group. CONCLUSIONS: SDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG. TRIAL REGISTRATION: ChiCTR1900026807(2019.10.23).

Association of obstructive sleep apnea symptoms with all-cause mortality and cause-specific mortality in adults with or without diabetes: A cohort study based on the NHANES.

BACKGROUND: The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all-cause and cause-specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study included participants from the NHANES 2005-2008 and 2015-2018 cycles with follow-up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves. RESULTS: A total of 13 761 participants with 7.68 ± 0.042 follow-up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all-cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all-cause mortality (HR 1.11 [95% CI: 1.03-1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03-1.33]). The relationship between OSAS.MAP10 and the risk of all-cause mortality and cancer mortality exhibited L-shaped curves in diabetes patients (both with nonlinear p values <.01). Further threshold effect analysis revealed that OSAS was positively related to death risk when OSAS.MAP10 exceeded the threshold scores. CONCLUSION: The relationship between OSAS and mortality differed among participants with or without diabetes. Individualized clinical treatment plans should be developed in clinical practice to reduce the risk of death for patients with different metabolic conditions.

Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample.

BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are associated with unfavorable outcomes following coronary artery bypass grafting (CABG). The purpose of this study was to compare in-hospital outcomes of patients with COPD alone versus OSA-COPD overlap after CABG. METHODS: Data of adults ≥ 18 years old with COPD who received elective CABG between 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS). Patients were divided into two groups: with OSA-COPD overlap and COPD alone. Propensity score matching (PSM) was employed to balance the between-group characteristics. Logistic and linear regression analyses determined the associations between study variables and inpatient outcomes. RESULTS: After PSM, data of 2,439 patients with OSA-COPD overlap and 9,756 with COPD alone were analyzed. After adjustment, OSA-COPD overlap was associated with a significantly increased risk of overall postoperative complications (adjusted odd ratio [aOR] = 1.12, 95% confidence interval [CI]: 95% CI: 1.01-1.24), respiratory failure/prolonged mechanical ventilation (aOR = 1.27, 95%CI: 1.14-1.41), and non-routine discharge (aOR = 1.16, 95%CI: 1.03-1.29), and AKI (aOR = 1.14, 95% CI: 1.00-1.29). Patients with OSA-COPD overlap had a lower risk of in-hospital mortality (adjusted odd ratio [aOR] = 0.53, 95% CI: 0.35-0.81) than those with COPD only. Pneumonia or postoperative atrial fibrillation (AF) risks were not significantly different between the 2 groups. Stratified analyses revealed that, compared to COPD alone, OSA-COPD overlap was associated with increased respiratory failure/prolonged mechanical ventilation risks among patients ≥ 60 years, and both obese and non-obese subgroups. In addition, OSA-COPD overlap was associated with increased risk of AKI among the older and obese subgroups. CONCLUSION: In US adults who undergo CABG, compared to COPD alone, those with OSA-COPD are at higher risks of non-routine discharge, AKI, and respiratory failure/prolonged mechanical ventilation, but a lower in-hospital mortality. No increased risk of AF was noted.

[Techniques for quantifying endotypes of obstructive sleep apnea].

Obstructive sleep apnea (OSA) is the frequent occurrence of apnea and/or hypopnea during sleep, leading to intermittent hypoxia, hypercapnia, and disruption of sleep architecture, further resulting in multisystem damage. The pathophysiological mechanisms include abnormal anatomical structure, low arousal threshold, high loop gain, and poor muscle reactivity, etc. As there are individual differences in the underlying mechanisms of OSA (i.e. endotypes), the effectiveness of treatment and prognosis may also vary according to these characteristics. Understanding the endotype of OSA is critical to understanding which patients are most likely to benefit from non-invasive ventilation therapy. Quantification of endotypes is central to the precision treatment of OSA and may provide the basis for accurate clinical treatment of OSA based on endotypes.

Association between obstructive sleep apnea and visceral adiposity index and lipid accumulation product: NHANES 2015-2018.

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.

Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2 / Relationship between obstructive sleep apnea and type 2 diabetes mellitus

Introducción: La asociación entre la apnea obstructiva del sueño (AOS) y el metabolismo de la glucosa sigue siendo controvertida. Este estudio investiga la relación entre la AOS y la diabetes mellitus tipo 2 (DM) y prediabetes (preDM) incidentes, así como el efecto del tratamiento con presión positiva continua en la vía aérea (CPAP) a largo plazo. Métodos: Estudio de seguimiento en cohorte retrospectiva clínica de pacientes con AOS y controles seleccionados de manera aleatoria. Los datos sobre DM incidente y preDM, así como de la CPAP se obtuvieron de los registros hospitalarios. La relación entre AOS basal y la DM incidente se examinó con modelos de regresión de Cox. Resultados: De un total de 356 pacientes, 169 con AOS y 187 controles fueron seguidos por una mediana de 98 meses; 47 enfermos (13,2%) desarrollaron DM y 43 (12,1%) preDM. La incidencia acumulada a los cinco años de DM fue de 10,7% (6,5-13,9%). De los sujetos con preDM en la muestra basal, 87% evolucionaron a DM incidente. Se demuestra que el índice de masa corporal (IMC), la hipoxia nocturna y el índice de apnea hipopnea (IAH) son factores de riesgo para el desarrollo de DM, y que la CPAP los disminuye. Conclusiones: Los pacientes con AOS tienen mayor probabilidad de desarrollar DM. Los factores de riesgo implicados son el IMC, la hipoxia nocturna y el IAH. El uso regular de CPAP a largo plazo se asoció con una disminución de estos. (AU)

Introduction: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. Methods: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. Results: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5–13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. Conclusions: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk. (AU)

Functional therapy and adenotonsillectomy clinical trial for class II malocclusion (FACT-II): protocol for a randomised controlled trial.

INTRODUCTION: Class II malocclusion with mandibular retrognathia is a common complication of paediatric obstructive sleep apnoea (OSA), often accompanied by transverse maxillary deficiency. In early orthodontic treatment, a twin block (TB) is a regular functional appliance for correcting this malocclusion. For paediatric OSA, the most common risk factor is adenotonsillar hypertrophy (AHT). Untreated AHT may lead to the persistence and worsening of obstructive sleep-disordered breathing traits, including habitual mouth breathing. Additionally, the clockwise mandibular rotation associated with AHT-induced pharyngeal crowding can undermine the effectiveness and stability of TB treatment. Adenotonsillectomy (T&A) is currently the first-line treatment for paediatric OSA. This proposed trial will investigate the impact of T&A surgery timing on the efficacy and stability of TB functional treatment in children with class II mandibular retrognathia and ATH. METHODS AND ANALYSIS: This will be a single-centre, parallel-group, superiority randomised controlled trial with participants randomised to intervention (T&A followed by TB treatment) or control arms (TB treatment followed by T&A) in a 1:1 ratio. A total of 40 patients aged 8-14 years, diagnosed with class II mandibular retrognathia and co-existing ATH-induced OSA, and indicated for both T&A surgery and TB treatment, will be recruited at the School and Hospital of Stomatology, Wuhan University. The primary outcomes will be the changes in the apnoea-hypopnoea index and the point A-nasion-point B angle from baseline to postorthodontic treatment between the two groups. Secondary outcomes will include other dental, skeletal, upper airway and soft tissue changes, as well as subjective sleep-related and oral-related quality of life. Outcome changes within each group and between groups will be analysed. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of the School and Hospital of Stomatology, Wuhan University (no. 2022-D07). The research findings will be faithfully disseminated through scientific conferences or published articles. TRIAL REGISTRATION NUMBER: ChiCTR2200061703 (https://www.chictr.org.cn).