Treatments for obstructive sleep apnea: CPAP and beyond.

Treatment options for obstructive sleep apnea include positive airway pressure and alternatives such as behavioral interventions, oral appliances, nasal expiratory positive airway pressure, negative pressure interventions, and surgical procedures. Certain drugs are also promising. An important aspect of the treatment includes troubleshooting the reasons for poor adherence to positive airway pressure treatment, discussing alternatives based either on individual preference or on phenotypic characterization of the sleep apnea, and managing expectations.

Respiratory Management of Patients With Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.

BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations. STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations. RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement. INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.

Obesity-associated sleep hypoventilation and increased adverse postoperative bariatric surgery outcomes in a large clinical retrospective cohort.

STUDY OBJECTIVES: Although obesity hypoventilation syndrome (OHS) is associated with increased morbidity and mortality, post-bariatric surgery OHS risk remains unclear due to often nonsystematic OHS assessments. METHODS: We leverage a clinical cohort with nocturnal CO2 monitoring during polysomnography to address the hypothesis that patients with obesity-associated sleep hypoventilation (OaSH; ie, stage II OHS) have increased adverse postoperative bariatric surgery outcomes. We retrospectively analyzed data from patients undergoing pre-bariatric surgery polysomnography at the Cleveland Clinic from 2011-2018. OaSH was defined by body mass index ≥ 30 kg/m2 and either polysomnography-based end-tidal CO2 ≥ 45 mmHg or serum bicarbonate ≥ 27 mEq/L. Outcomes considered were as follows: intensive care unit stay, intubation, tracheostomy, discharge disposition other than home or 30-day readmission individually and as a composite, and all-cause mortality. Two-sample t test or Wilcoxon rank-sum test for continuous variables and chi-square or Fisher's exact test for categorical variables were used for OaSH vs non-OaSH comparisons. All-cause mortality was compared using Kaplan-Meier estimation and Cox proportional hazards models. RESULTS: The analytic sample (n = 1,665) was aged 45.2 ± 12 years, 20.4% were male, had a body mass index of 48.7 ± 9 kg/m2, and 63.6% were White. OaSH prevalence was 68.5%. OaSH patients were older and more likely to be male with a higher BMI, apnea-hypopnea index, and glycated hemoglobin. The composite outcome was higher in OaSH vs non-OaSH patients (18.9% vs 14.3%, P = .021). Although some individual outcomes were respectively higher in OaSH vs non-OaSH patients, differences were not statistically significant: intubation (1.5% vs 1.3%, P = .81) and 30-day readmission (13.8% vs 11.3%, P = .16). Long-term mortality (median follow-up: 22.9 months) was not significantly different between groups, likely due to overall low event rate (hazard ratio = 1.39, 95% confidence interval: 0.56, 3.42). CONCLUSIONS: In this largest sample to date of systematically phenotyped OaSH in a bariatric surgery cohort, we identify increased postoperative morbidity in those with sleep-related hypoventilation in stage II OHS when a composite outcome was considered, but individual contributors of intubation, intensive care unit admission, and hospital length of stay were not increased. Further study is needed to identify whether perioperative treatment of OaSH improves post-bariatric surgery outcomes. CITATION: Chindamporn P, Wang L, Bena J, et al. Obesity-associated sleep hypoventilation and increased adverse postoperative bariatric surgery outcomes in a large clinical retrospective cohort. J Clin Sleep Med. 2022;18(12):2793-2801.

Diagnostic and therapeutic challenges of chronic obstructive pulmonary disease in the elderly.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) imposes a large burden on the global population and even more so for the elderly who face significant obstacles in the diagnosis, management, and psychosocial effects of the disease. This review describes the current challenges and key points in the management of COPD in the elderly. RECENT FINDINGS: Lower limit rather than fixed cut off of the FEV1/FVC ratio can improve the diagnosis and better predict COPD mortality. High relative to standard dose influenza vaccination reduces confirmed cases of influenza overall and reduces hospitalizations in older nursing home residents. Simple interventions that include electronic health record tracking can significantly improve vaccination rates. Although many inhaler and nebulized medications are available for the elderly, the final regimen is usually determined by a combination of expense, issues with proper device use (from difficulty with coordination, hand grip, inspiratory flows or cognitive function) and the side effect profile. Fortunately, the switch to cheaper or better covered alternatives can be well tolerated with improvement in adherence and exacerbations of COPD. Finally, caution should be made against ageism, which may be a factor in the recommendation of rehabilitation or palliative care in the elderly COPD patient, as both are underused despite evidence of benefit. SUMMARY: Although care for the elderly COPD patient can be difficult, we summarize key points that the physician should be cognizant of to provide comprehensive care.

Elucidating Predictors of Obesity Hypoventilation Syndrome in a Large Bariatric Surgery Cohort.

Rationale: Although understanding predictors of obesity hypoventilation syndrome (OHS), a condition associated with increased morbidity and mortality, is of key importance for risk prediction, existing characterization is limited.Objectives: We hypothesize that OHS patients referred for bariatric surgery have more severe obstructive sleep apnea and metabolic derangements compared with their eucapnic counterparts.Methods: A total of 1,718 patients undergoing polysomnography with end-tidal CO2 monitoring prior to bariatric surgery at Cleveland Clinic from September 2011 to September 2018 were included. OHS was defined by body mass index (BMI) ≥ 30 kg/m2 and either polysomnography-based end-tidal CO2 ≥ 45 mm Hg or serum bicarbonate levels ≥ 27 mEq/L based on the updated European Respiratory Society guidelines. Unadjusted and multivariable logistic regression models (odds ratio; 95% confidence interval) were used to examine OHS predictors consisting of factors in domains of patient characteristics, polysomnography (cardiorespiratory and sleep architecture), laboratory, and metabolic parameters.Results: The analytic sample comprised 1,718 patients with the following characteristics: age of 45.3 ± 12.1 years, 20.7% were male, BMI = 48.6 ± 9 kg/m2, and 63.6% were white individuals. OHS prevalence was 68.4%. Unadjusted analyses revealed a 1.5% increased odds of OHS (1.01; 1.00-1.03) per 1-unit BMI increase, 1.7% (1.02; 1.01-1.02) per 1% increase in sleep time SaO2 < 90%, 12% increase (1.12; 1.03-1.22) per 1-U increase in hemoglobin A1c, and 3.4% increased odds (1.03; 1.02-1.05) per 5-U increase in apnea-hypopnea index. The association of apnea-hypopnea index with OHS persisted after adjustment for age, sex, race, and BMI and its comorbidities (1.02; 1.01-1.04).Conclusions: OHS was highly prevalent in patients referred for bariatric surgery by more than two-thirds. Even after consideration of confounders including obesity, obstructive sleep apnea remained a strong OHS predictor, as were increasing age, male sex, nocturnal hypoxia, and impaired long-term glucose control. These findings can inform OHS risk stratification in bariatric surgery and set the stage for experimental studies to examine sleep-related respiratory and metabolic contributions to hypoventilation.

Noninvasive positive pressure ventilation in stable patients with COPD.

PURPOSE OF REVIEW: Long-term noninvasive positive pressure ventilation (NIV) used to be a controversial form of therapy for patients with stable hypercapnic chronic obstructive pulmonary disease (SH-COPD). New evidence described in this review defines the optimal settings, timing and target population for NIV utilization in SH-COPD necessary to maximize its benefit. RECENT FINDINGS: NIV, when titrated appropriately, leads to improved clinical outcomes. High inspiratory positive airway pressures aimed at decreasing CO2 levels can ensure NIV success in SH-COPD. NIV initiated when patients remain hypercapnic whereas in a clinical stable state following an acute exacerbation can prolong the time to a readmission. Technological advances in NIV algorithms and remote monitoring have the potential to improve use and titration. NIV and portable NIV improve exercise tolerance and may accentuate the benefits derived from pulmonary rehabilitation alone. SUMMARY: Use of high-intensity NIV in SH-COPD is beneficial yet appropriate patient selection and implementation is paramount.

Pattern of lung function decline in patients with amyotrophic lateral sclerosis: implications for timing of noninvasive ventilation.

BACKGROUND: The course of lung function decline in amyotrophic lateral sclerosis (ALS) and the effect of noninvasive positive-pressure ventilation (NIPPV) on that decline are uncertain. We sought to model lung function decline, determine when NIPPV is initiated along that course, and assess its impact on the course of decline. METHODS: An observed sigmoid pattern of forced vital capacity decline was reproduced with a four-parameter nonlinear mixed-effects logistic model. RESULTS: Analyses were performed on 507 patients overall and in 353 patients for whom a determination of adherence to NIPPV was ascertained. A sigmoid bi-asymptotic model provided a statistical fit of the data and showed a period of stable vital capacity, followed by an accelerated decline, an inflection point, then a slowing in decline to a plateau. By the time NIPPV was initiated in accordance with reimbursement guidelines, vital capacity had declined by ≥85% of the total range. Nearly half of the total loss of vital capacity occurred over 6.2 months centred at an inflection point occurring 17 months after disease onset and 5.2 months before initiation of NIPPV at a vital capacity of about 60%. Fewer bulbar symptoms and a faster rate of decline of lung function predicted adherence to NIPPV, but the intervention had no impact on final vital capacity. CONCLUSIONS: In patients with ALS, vital capacity decline is rapid but slows after an inflection point regardless of NIPPV. Initiating NIPPV along reimbursement guidelines occurs after ≥85% of vital capacity loss has already occurred.

Variation in noninvasive ventilation use in amyotrophic lateral sclerosis.

OBJECTIVE: We sought to examine prevalence and predictors of noninvasive ventilation (NIV) in a composite cohort of patients with amyotrophic lateral sclerosis (ALS) followed in a clinical trials setting (Pooled Resource Open-Access ALS Clinical Trials database). METHODS: NIV initiation and status were ascertained from response to question 12 of the revised ALS Functional Rating Scale (ALSFRS-R). Factors affecting NIV use in patients with forced vital capacity (FVC) ≤50% of predicted were examined. Predictors of NIV were evaluated by Cox proportional hazard models and generalized linear mixed models. RESULTS: Among 1,784 patients with 8,417 simultaneous ALSFRS-R and FVC% measures, NIV was used by 604 (33.9%). Of 918 encounters when FVC% ≤50%, NIV was reported in 482 (52.5%). Independent predictors of NIV initiation were lower FVC% (hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.17-1.37 for 10% drop), dyspnea (HR 2.62, 95% CI 1.87-3.69), orthopnea (HR 4.09, 95% CI 3.02-5.55), lower bulbar and gross motor subscores of ALSFRS-R (HRs 1.09 [95% CI 1.03-1.14] and 1.13 [95% CI 1.07-1.20], respectively, per point), and male sex (HR 1.73, 95% CI 1.31-2.28). Adjusted for other variables, bulbar onset did not significantly influence time to NIV (HR 0.72, 95% CI 0.47-1.08). Considerable unexplained variability in NIV use was found. CONCLUSION: NIV use was lower than expected in this ALS cohort that was likely to be optimally managed. Absence of respiratory symptoms and female sex may be barriers to NIV use. Prospective exploration of factors affecting adoption of NIV may help bridge this gap and improve care in ALS.

Impact of a Post-Discharge Integrated Disease Management Program on COPD Hospital Readmissions.

BACKGROUND: Readmission following a hospitalization for COPD is associated with significant health-care expenditure. METHODS: A multicomponent COPD post-discharge integrated disease management program was implemented at the Cleveland Clinic to improve the care of patients with COPD and reduce readmissions. This retrospective study reports our experience with the program. Groups of subjects who were exposed to different components of the program were compared regarding their readmission rates. Multivariate logistic regression analysis was performed to build predictive models for 30- and 90-d readmission. RESULTS: One hundred sixty subjects completed a 90-d follow-up, of which, 67 attended the exacerbation clinic, 16 subjects received care coordination, 51 subjects completed both, and 26 subjects did not participate in any component despite referral. Thirty- and 90-d readmission rates for the entire group were 18.1 and 46.2%, respectively. Thirty- and 90-d readmission rates for the individual groups were: exacerbation clinic, 11.9 and 35.8%; care coordination, 25.0 and 50.0%; both, 19.6 and 41.2%; and neither, 26.9 and 80.8%, respectively. The model with the best predictive ability for 30-d readmission risk included the number of hospitalizations within the previous year and use of noninvasive ventilation (C statistic of 0.84). The model for 90-d readmission risk included receiving any component of the post-discharge integrated disease management program, the number of hospitalizations, and primary care physician visits within the previous year (C statistic of 0.87). CONCLUSIONS: Receiving any component of a post-discharge integrated disease management program was associated with reduced 90-d readmission rate. Previous health-care utilization and lung function impairment were strong predictors of readmission.

Modeling of Lung Function Recovery in Neuralgic Amyotrophy With Diaphragm Impairment.

BACKGROUND: Neuralgic amyotrophy is an inflammatory peripheral nerve disorder in which phrenic nerve involvement can lead to diaphragm paralysis. The prevalence, magnitude, and time course of diaphragm recovery are uncertain. METHODS: This study modeled the course of recovery of lung function in 16 subjects with diaphragm impairment from neuralgic amyotrophy. The first and last available vital capacity, sitting-to-supine decline in vital capacity, and maximal inspiratory pressures were compared. RESULTS: An asymptotic regression model analysis in 11 subjects with at least partial recovery provided estimates of the vital capacity at onset (47%, 95% CI 25-68%), the final vital capacity (81%, 95% CI 62-101%), and the half-time to recovery (22 months, 95% CI 15-43 months). In those subjects, there was a significant improvement between the first and last measured FVC (median 44-66%, P = .004) and maximal inspiratory pressure (mean 34-51%, P = .004). Five subjects (31%) with complete recovery had a final sitting-to-supine drop of vital capacity of 16% and a maximal predicted inspiratory pressure of 63%. CONCLUSIONS: Sixty-nine percent of subjects with diaphragm impairment from neuralgic amyotrophy experience recovery of lung function and diaphragm strength, but recovery is slow and may be incomplete.

Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events.

Neuromuscular weakness in chronic obstructive pulmonary disease: chest wall, diaphragm, and peripheral muscle contributions.

PURPOSE OF REVIEW: Chronic obstructive lung disease affects the lung parenchyma and airways leading to well described effects in respiratory function. This review describes the current knowledge and advances regarding neuromuscular function and chest wall mechanics, which are affected in chronic obstructive pulmonary disease (COPD). RECENT FINDINGS: In COPD, progressive lung hyperinflation becomes constrained by a chest wall with decreasing capacity to expand, resulting in respiratory muscle inefficiency. There is evidence of neuromuscular uncoupling, that is, the respiratory muscle is unable to increase its output in proportion to increasing neural signals. COPD patients also have evidence of altered peripheral muscles function. The end effect of all these pathological changes is neuromuscular weakness. SUMMARY: Respiratory and peripheral muscles dysfunction is found in patients with COPD. This manifests clinically as dyspnea, poor exercise capacity, and decreased quality of life. We have clear evidence that rehabilitation helps several aspects of patients with COPD. Further understanding of the physiopathology is needed to improve our therapeutic and rehabilitation strategies.

Treating and preventing acute exacerbations of COPD.

Acute exacerbations of chronic obstructive pulmonary disease (COPD)--characterized by shortness of breath, increased sputum production, increased purulence, or a combination of these signs--are costly and can have major impacts on the patient's health. Corticosteroids, antibiotics, and bronchodilators are the cornerstones of prevention and therapy, with mucolytics, oxygen supplementation, and ventilatory support also advisable for some patients. Treatment should be evidence-based and tailored to the patient's history and present needs.

A 26-Year-Old Woman With Systemic Lupus Erythematosus Presenting With Orthopnea and Restrictive Lung Impairment.

A 26-year-old white woman diagnosed with systemic lupus erythematosus (SLE) presented with left shoulder pain and a three-pillow orthopnea. Lupus was diagnosed at age 21 years when she developed arthritis, and she has been maintained on prednisone (2.5 mg) and mycophenolate (500 mg bid). In the course of evaluating her new symptoms, imaging revealed a small left pleural effusion with exudative characteristics on a diagnostic thoracentesis, but there was no evidence of infection. Her immunosuppression treatment was increased to 1,000 mg bid of mycophenolate and 20 mg of prednisone. Three months later, she presented to our clinic with worsening six-pillow orthopnea, such that she usually slept with 45° truncal elevation on a recliner at night. She was unable to lie flat. Her dyspnea was worse in the mornings, and she described having to "gasp" for air.

Determinants of Wake Pco2 and Increases in Wake Pco2 over Time in Patients with Obstructive Sleep Apnea.

RATIONALE: The progression from obesity and obstructive sleep apnea to obesity with hypoventilation and daytime hypercapnia may relate to features of sleep-disordered breathing events that affect loading and unloading of carbon dioxide. OBJECTIVES: To determine whether the wake Pco2 increases over time in untreated obstructive sleep apnea, and whether that increase is explained by changes in sleep-disordered breathing event duration, interevent duration, or postevent ventilation amplitude. METHODS: We selected 14 adults who had two polysomnographic studies more than 1 year apart because of untreated or suboptimally treated moderate to severe obstructive sleep apnea. Demographic and polysomnographic data were reviewed for both sets of studies, including the evening wake end-tidal CO2, the ratio of mean event to mean interevent duration (subsuming apneas and hypopneas), and the ratio of mean post- to preevent breath amplitude. MEASUREMENT AND MAIN RESULTS: The mean (SD) wake end-tidal Pco2 increased between studies from 35.9 (4.2) to 39.5 (3.9) mm Hg (P < 0.005). The wake end-tidal CO2 correlated inversely with the post- to pre-event breath amplitude and positively with the ratio of mean event to mean interevent duration and with body mass index. However, those three variables were not significantly changed between the two studies. The wake end-tidal CO2 did not correlate with the apnea-hypopnea index or age. There was a significant increase in bicarbonate level between studies (median, 24.0-26.5 mmol/L; P = 0.01). CONCLUSIONS: In our study cohort, wake end-tidal CO2 correlated with body mass index and features of sleep apnea that influence the balance of loading and unloading of CO2. However, those features remained fixed over time, even as the wake Pco2 and bicarbonate levels increased with untreated sleep apnea.

Expiratory Time Constant and Sleep Apnea Severity in the Overlap Syndrome.

STUDY OBJECTIVES: Lung mechanics in the overlap of COPD and sleep apnea impact the severity of sleep apnea. Specifically, increased lung compliance with hyperinflation protects against sleep apnea, whereas increased airway resistance worsens sleep apnea. We sought to assess whether the expiratory time constant, which reflects lung mechanics, is associated with sleep apnea severity in such patients. METHODS: Polysomnographies in 34 subjects with the overlap syndrome were reviewed. Three time constants were measured for each of up to 5 stages (wake, NREM stages, and REM). The time constants were derived by fitting time and pressure coordinates on the expiratory portion of a nasal pressure signal along an exponentially decaying equation, and solving for the time constant. Demographics, morphometrics, wake end-tidal CO2, right diaphragmatic arc on a chest radiograph, and the apnea-hypopnea index (AHI) were recorded. RESULTS: The time constant was not associated with age, gender, body mass index, right diaphragmatic arc, or wake end-tidal CO2, and was not significantly different between sleep stages. A mean time constant (TC) was therefore obtained. Subjects with a TC > 0.5 seconds had a greater AHI than those with a TC ≤ 0.5 seconds (median AHI 58 vs. 18, respectively, p = 0.003; Odds ratio of severe sleep apnea 10.6, 95% CI 3.9-51.1, p = 0.005). CONCLUSIONS: A larger time constant in the overlap syndrome is associated with increased odds of severe sleep apnea, suggesting a greater importance of airway resistance relative to lung compliance in sleep apnea causation in these subjects.