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Arizona Respiratory Center, University of Arizona, TucsonDepartment of Medicine, University of Arizona, TucsonCREAL Centre and Universitat Pompeu Fabra, Barcelona, Spain
Hospitalization of patients with chronic obstructive pulmonary disease creates a huge healthcare burden. Positive airway pressure therapy is sometimes used in patients with chronic obstructive pulmonary disease, but the possible impact on hospitalization risk remains controversial. We studied the hospitalization risk of patients with chronic obstructive pulmonary disease before and after initiation of various positive airway pressure therapies in a “real-world” bioinformatics study.
Methods
We performed a retrospective analysis of administrative claims data of hospitalizations in patients with chronic obstructive pulmonary disease who received or did not receive positive airway pressure therapy: continuous positive airway pressure, bilevel positive airway pressure, and noninvasive positive pressure ventilation using a home ventilator.
Results
The majority of 1,881,652 patients with chronic obstructive pulmonary disease (92.5%) were not receiving any form of positive airway pressure therapy. Prescription of bilevel positive airway pressure (1.5%), continuous positive airway pressure (5.6%), and noninvasive positive pressure ventilation (<1%) in patients with chronic obstructive pulmonary disease demonstrated geographic-, sex-, and age-related variability. After adjusting for confounders and propensity score, noninvasive positive pressure ventilation (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.13-0.27), bilevel positive airway pressure (OR, 0.42; 95% CI, 0.39-0.45), and continuous positive airway pressure (OR, 0.70; 95% CI, 0.67-0.72) were individually associated with lower hospitalization risk in the 6 months post-treatment when compared with the 6 months pretreatment but not when compared with the baseline period between 12 and 6 months before treatment initiation. Stratified analysis suggests that comorbid sleep-disordered breathing, chronic respiratory failure, heart failure, and age less than 65 years were associated with greater benefits from positive airway pressure therapy.
Conclusion
Initiation of positive airway pressure therapy was associated with reduction in hospitalization among patients with chronic obstructive pulmonary disease, but the causality needs to be determined by randomized controlled trials.
Initiation of positive airway pressure therapy was associated with a reduction in hospitalization among patients with chronic obstructive pulmonary disease.
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Only 7.5% of 1,881,652 patients with chronic obstructive pulmonary disease were receiving some form of positive airway pressure therapy.
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Comorbid sleep-disordered breathing and chronic respiratory failure were associated with greater benefits from positive airway pressure therapy.
Chronic obstructive pulmonary disease is the third leading cause of death in the United States.
Trends in chronic bronchitis and emphysema. Morbidity and Mortality. American Lung Association Epidemiological and Statistics unit Research and Program Services 2013; Available at: http://www.lung.org/assets/documents/research/copd-trend-report.pdf. Accessed November 23, 2016.
Approximately 12.7 million US adults were estimated to have chronic obstructive pulmonary disease in 2013, which is an important cause of hospitalization in our aged population with a discharge rate of 23.2 per 10,000 population with related healthcare costs approximating $50 billion.
A propensity-matched retrospective analysis to identify predictors of rehospitalization for patients with chronic obstructive pulmonary disease (COPD). C51. Hospitalization and readmission in chronic obstructive pulmonary disease:.
In an effort to reduce hospitalization in patients with chronic obstructive pulmonary disease, Medicare currently penalizes hospitals for 30-day readmission of patients with chronic obstructive pulmonary disease.
Although various medication-based strategies are being developed to reduce hospitalization in patients with chronic obstructive pulmonary disease, there is an expressed need for studies to evaluate different and nonmedication approaches.
Observational studies from a multicenter European study and a single-center US study suggest that positive airway pressure therapy treatments, such as continuous positive airway pressure therapy or noninvasive positive pressure ventilation delivered by home ventilators, are associated with lower hospitalizations in patients with chronic obstructive pulmonary disease.
Moreover, in 2 European randomized controlled trials, bilevel positive airway pressure therapy (bilevel positive airway pressure) has been shown to reduce mortality in stable patients with severe chronic obstructive pulmonary disease but not hospitalizations.
Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.
Consequently, it is unclear whether positive airway pressure therapy is an effective intervention that can reduce hospitalization in patients with chronic obstructive pulmonary disease in the United States.
We aimed to study the hospitalization risk of patients with chronic obstructive pulmonary disease before and after initiation of various positive airway pressure therapy device prescriptions in a “real-world” bioinformatics analysis of administrative claims data with the intent that such a retrospective study could inform future randomized controlled trials.
Administrative claims data in the Truven Health MarketScan Database were analyzed from January 1, 2009, to October 31, 2014. Records of patients with at least 2 chronic obstructive pulmonary disease–related claims (≥1 day apart) during this time period were included. Chronic obstructive pulmonary disease–related claims were defined using the International Classification of Diseases, Ninth Revision diagnosis codes (Supplementary Table 1, available online). Individuals with claims for a bilevel positive airway pressure, continuous positive airway pressure, or noninvasive positive pressure ventilation device during this time period based on Current Procedural Terminology codes (Supplementary Table 2, available online) were included if they were aged more than 40 years and were continuously enrolled for 12 months before and 6 months after their date of claim (“index date”). The hospitalizations in the 12 months before and 6 months after their index date were assessed. In addition, “medication only” (control) groups who did not receive any form of positive airway pressure therapy were identified for each of the 3 treatment groups. The index date for each control was defined as a date of a chronic obstructive pulmonary disease–related claim. The medication only groups were frequency matched for similar healthcare use, that is, a similar median number of chronic obstructive pulmonary disease claims in the previous 12 months of the index date compared with the treatment groups. This study was reviewed and approved by the University of Arizona Institutional Review Board (Protocol #1602358894) as an exempt study.
Outcomes and Time Periods
Data were analyzed on the basis of 3 time periods referenced to the index date: The first time period (“baseline”) occurred −360 days to −181 days; the “pretreatment” occurred −180 days to 0 days; and the “post-treatment” occurred +1 day to +180 days from the index date. Any hospitalization was defined as any reported claim for an inpatient admission and chronic obstructive pulmonary disease–related hospitalization was defined as any hospitalization with a primary diagnosis of chronic obstructive pulmonary disease.
Covariates and Propensity Score
Potential confounders that were considered include demographics, comorbidities, and chronic obstructive pulmonary disease–related prescriptions. Demographics included age, sex, region (Northeast, Midwest, South, West), and insurance type at the index date (Table 1). Twenty-two common comorbidities (Table 2) that that are generally associated with increased risk for hospitalization and were reported as a claim −360 days to the index date were included as covariates in the regression models (Table 3, footnote). Additional covariates and methodology are provided in the online supplement, available online. To account for baseline characteristics that may have influenced the prescription of positive airway pressure device, a propensity score was developed using sleep-disordered breathing, chronic respiratory failure, and restrictive thoracic disorder to predict treatment assignment (Supplementary Table 3, available online).
Differences in baseline characteristics and comorbidities across positive airway pressure groups and between positive airway pressure treated versus medication only groups were assessed using the chi-square test. To model the relationship between each device and hospitalization risk, and to account for the longitudinal and correlated nature of these binary outcome data, generalized estimating equations with binomial family, logit link, and unstructured correlation structure were used. The 2 main models of interest investigated the relationship between the treatment devices and any hospitalization (primary end point) or chronic obstructive pulmonary disease–related hospitalizations (secondary end point). In addition, we examined the effect of each device compared with its matched medication-only control group for any and chronic obstructive pulmonary disease–related hospitalizations, for a total of 6 additional models after adjusting for various covariates including the propensity score. Linear contrasts were used to test for differences in the hospitalization risk in the 6 months post-treatment (period 3) when compared with the 6 months pretreatment (period 2) across positive airway pressure groups. Subjects who were prescribed their treatment device near the time of a hospitalization were included in main analyses, but sensitivity analyses were performed after excluding hospitalization events occurring ±12 days from the index date. Furthermore, all models also were stratified by subjects with and without sleep-disordered breathing, congestive heart failure, age less than or more than 65 years, and chronic respiratory failure. Statistical analyses were performed with Stata version 14.0 (StataCorp LP, College Station, Tex).
Results
Baseline Characteristics and Covariates
Figure 1 shows the flowchart for patients included in this study. There were a total of 1,881,652 enrollees with at least 2 chronic obstructive pulmonary disease–related claims (≥1 day apart), of whom 28,774 enrollees were initiated on bilevel-positive airway pressure therapy, 112,119 enrollees were initiated on continuous positive airway pressure therapy, and 1011 enrollees were initiated on noninvasive positive pressure ventilation therapy. After excluding subjects who did not meet the continuous enrollment or age criteria, 9156 subjects on bilevel-positive airway pressure, 39,385 subjects on continuous positive airway pressure, and 315 subjects on noninvasive positive pressure ventilation were included in the analysis. The medication only groups that were generated after matching for the median chronic obstructive pulmonary disease–related claims were as follows: There were 289,636 subjects in the matched bilevel-positive airway pressure control group with a median number of 5 (interquartile range [IQR], 3-10) chronic obstructive pulmonary disease claims per year, which was comparable to chronic obstructive pulmonary disease claims per year for the bilevel-positive airway pressure–treated group (median, 5; IQR, 1-17). Likewise, the chronic obstructive pulmonary disease claims per year for the 464,684 subjects in the matched continuous positive airway pressure control group (median 3; IQR, 2-5) were comparable to those in the continuous positive airway pressure group (median, 2; IQR, 0-8). Also, the chronic obstructive pulmonary disease claims per year for the 80,637 subjects in the matched noninvasive positive pressure ventilation control group (median, 27; IQR, 18-37) were comparable to those in the noninvasive positive pressure ventilation–treated group (median 27; IQR, 7-54).
Figure 1Flow chart of patients with chronic obstructive pulmonary disease who received various forms of positive airway pressure therapy, such as bilevel-positive airway pressure therapy, continuous positive airway pressure therapy, and home ventilators that delivered noninvasive positive pressure ventilation therapy. Enrollees with hospital admission discharge status of “died” that occurred within 6 months of treatment initiation were as follows: bilevel-positive airway pressure (N = 108 [0.39%]), continuous positive airway pressure (N = 106 [0.1%]), noninvasive positive pressure ventilation (N = 16 [1.69%]), nontreated frequency-matched controls for continuous positive airway pressure (N = 672 [0.05%]), frequency-matched controls for bilevel-positive airway pressure (N = 3192 [1.1%]), and frequency-matched controls for noninvasive positive pressure ventilation (N = 1502 [1.86%]). COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; NIPPV = nasal intermittent positive pressure ventilation; PAP = positive airway pressure. ∗Enrollees with continuous health plan coverage 12 months before and 6 months after index date.
The majority of patients with chronic obstructive pulmonary disease (92.5%) were not receiving any form of positive airway pressure therapy (Figure 1), with a significant minority receiving positive airway pressure therapy: continuous positive airway pressure (5.6%), bilevel-positive airway pressure (1.5%), and noninvasive positive pressure ventilation therapy (<1%). There was significant geographic-, sex-, and age-related variability with regard to the type of positive airway pressure therapy prescribed to patients with chronic obstructive pulmonary disease (Supplementary Figure 1, available online, and Table 1). Patients receiving noninvasive positive pressure ventilation were older and resided in the southern region compared with patients who received bilevel-positive airway pressure or continuous positive airway pressure therapy (Table 1).
Comorbidities are shown by each treatment in Table 2, and the corresponding International Classification of Diseases, Ninth Revision codes are available in Supplementary Table 4 (available online). In general, there were more comorbidities in the patients receiving noninvasive positive pressure ventilation than those receiving bilevel-positive airway pressure or continuous positive airway pressure therapy (Table 2), and cardiovascular disease was the most common comorbidity for all 3 groups of patients.
In particular, acute and chronic respiratory failure were more common in patients receiving noninvasive positive pressure ventilation than in the other 2 groups. Prescription of any medication for chronic obstructive pulmonary disease grouped by drug mechanism of action was determined (Supplementary Table 5, available online). Supplemental oxygen therapy, short-acting beta-agonists, and systemic corticosteroids were the most common medications and were more likely to be prescribed to the patients receiving noninvasive positive pressure ventilation therapy in the 12 months before noninvasive positive pressure ventilation being issued. Such medication prescription data combined with worse comorbidities and other baseline characteristics (eg, age) in the noninvasive positive pressure ventilation group indicate the possibility of confounding by indication for the level of support rendered by the type of positive airway pressure therapy with progressively greater degree of respiratory muscle unloading accomplished by continuous positive airway pressure, bilevel positive airway pressure, and noninvasive positive pressure ventilation therapy using a home ventilator. Such indication bias provides the rationale for the matched “medication only” controls and propensity score adjustment.
Association Between Device Use and Hospitalizations
Crude hospitalizations by each treatment group are reported for the 3 time periods in Supplementary Figure 2 (available online) for any hospitalization and for chronic obstructive pulmonary disease–related hospitalization (Supplementary Table 6, available online). For all periods, crude hospitalization rates were highest in the noninvasive positive pressure ventilation group. For all treatment groups, hospitalization rates peaked in the pretreatment period, and in the post-treatment period the hospitalizations returned to levels during the baseline period. After adjusting for various covariates and propensity score, positive airway pressure therapy was associated with the reduction of any hospitalizations or chronic obstructive pulmonary disease–related hospitalizations (Figure 2) in the post-treatment period when compared with the pretreatment period (Supplementary Table 7, available online). For any hospitalizations, the observed reduction was greater in patients receiving noninvasive positive pressure ventilation than those receiving continuous positive airway pressure (P <.001) or bilevel positive airway pressure therapy (P <.001). For chronic obstructive pulmonary disease–related hospitalizations, the observed reductions in patients receiving noninvasive positive pressure ventilation therapy were greater than in patients receiving continuous positive airway pressure therapy (P = .01).
Figure 2Longitudinal associations (adjusted odds ratios) for any and chronic obstructive pulmonary disease–related hospitalization in patients with chronic obstructive pulmonary disease comparing 6 months after device treatment (+1 to +180 days) with 6 months before device treatment (−180 days to 0 days) periods. BIPAP = bilevel positive airway pressure; CI = confidence interval; COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; NIPPV = nasal intermittent positive pressure ventilation; OR = odds ratio.
Considering that positive airway pressure therapy initiation in an ambulatory setting may be different than in recently hospitalized patients, we stratified the data by whether the positive airway pressure device was initiated within ±12 days of a hospitalization (Supplementary Tables 8 and 9, available online). Such stratification did not materially change the results. Crude hospitalization rates and adjusted odds ratios for both the positive airway pressure treatment and corresponding matched medication only groups are provided in Supplementary Table 10 (available online) and Table 3, respectively. In general, patients receiving positive airway pressure treatment had more hospitalizations in the pretreatment period than in the post-treatment period (Supplementary Figure 2 and Supplementary Table 6, available online) (P <.0001). A similar trend was observed in the medication-only group, which had a higher hospitalization risk in the 6 months preceding the index date compared with the 6 months after the index date. Stratification by the presence or absence of comorbid sleep-disordered breathing did not seem to materially modify the results (Supplementary Tables 11 and 12, available online), which suggests that comorbid sleep-disordered breathing in patients with chronic obstructive pulmonary disease may be associated with a greater reduction in hospitalization. In patients with chronic obstructive pulmonary disease and comorbid sleep-disordered breathing, noninvasive positive pressure ventilation seemed to be associated with greater reductions in any hospitalization and in chronic obstructive pulmonary disease–related hospitalizations (Supplementary Table 12, available online). Likewise, comorbid chronic respiratory failure (Supplementary Tables 13 and 14, available online), age less than 65 years (Supplementary Tables 15 and 16, available online), and comorbid congestive heart failure (Supplementary Tables 17 and 18, available online) were associated with a greater reduction in hospitalizations in patients with chronic obstructive pulmonary disease (Figure 3).
Figure 3Longitudinal associations (adjusted odds ratios) for any and chronic obstructive pulmonary disease–related hospitalization in patients with chronic obstructive pulmonary disease comparing 6 months after device treatment (+1 to +180 days) with 6 months before device treatment (−180 days to 0 days) periods after stratification by patients with and without sleep-disordered breathing (left upper), with and without chronic respiratory failure (right upper); age <65 or >65 years (left lower) and with and without heart failure (right lower). CI = confidence interval; CPAP = continuous positive airway pressure; NIPPV = nasal intermittent positive pressure ventilation; OR = odds ratio; PAP = positive airway pressure; SDB = sleep-disordered breathing.
In this “real-world” study derived from administrative claims data, positive airway pressure therapy was generally prescribed to older patients with chronic obstructive pulmonary disease with greater comorbidities and greater health care use with significant geographic variability in such practice. Among patients with chronic obstructive pulmonary disease who received positive airway pressure therapy, initiation of treatment was associated with a reduction in hospitalization risk in the subsequent 6 months compared with the 6 months that preceded positive airway pressure initiation, and this improvement was particularly strong in the noninvasive positive pressure ventilation group. However, the potential causal nature of these associations should be interpreted with caution for the following reasons. First, there was strong evidence for potential confounding by indication with patients with comorbidities being more likely to receive positive airway pressure therapy or a more powerful positive airway pressure therapy device capable of greater respiratory muscle unloading that warranted the development and adjustment for propensity scores. Second, for all treatment groups, we found hospitalization rates to peak in the 6-month period preceding the initiation of positive airway pressure therapy, suggesting that the prescription of the positive airway pressure device may have been a component of a broader management strategy and may have been accompanied by other types of therapeutic interventions possibly affecting the risk for subsequent hospitalizations. This possibility is supported by the observation of similar improvements in hospitalization risk occurring among medication only (control) groups despite these patients not receiving any positive airway pressure therapy. Nevertheless, noninvasive positive pressure ventilation therapy showed the largest reduction in hospitalization (Table 3). Therefore, although our efforts to adjust analyses using propensity scores continued to indicate significant improvements particularly after initiation of more powerful positive airway pressure therapy devices such as noninvasive positive pressure ventilation, we cannot determine from our observational data whether these effects are actually related to the positive airway pressure therapy or any other interventions and factors that took place at the time of positive airway pressure initiation and whether the baseline differences in comorbidities across the 3 treatment groups may have contributed to some of the observed effects. Last, there is a possibility of loss of, or change to, insurance coverage that may not have been captured by the defined continuous enrollment criteria and may have changed the population “at risk” for hospitalization. Nevertheless, it is unlikely that there would have been a systematic difference in such loss of insurance coverage in 1 or the other groups. Despite such limitations, our “real-world” findings can be said to support the need for pragmatic and adequately powered randomized controlled trials of positive airway pressure therapies in patients with chronic obstructive pulmonary disease and provide preliminary data for performing sample size estimations.
Initiation of bilevel-positive airway pressure therapy in patients with severe stable chronic obstructive pulmonary disease with significant hypercapnia (partial pressure of carbon dioxide >52 mm Hg) has been shown to reduce mortality but to have no effect on hospitalization.
Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.
However, there are prospective observational data from a large European study that continuous positive airway pressure therapy is associated with reduction of a composite outcome of hospitalization and mortality in patients with chronic obstructive pulmonary disease and coexistent sleep-disordered breathing.
However, the use of any positive airway pressure therapy in patients with chronic obstructive pulmonary disease regardless of the presence of sleep-disordered breathing is uncommon in the United States, with a majority of patients with chronic obstructive pulmonary disease (92.5%) not receiving any form of positive airway pressure therapy. In contrast, recent data suggest that 30% of European patients with chronic obstructive pulmonary disease received prescription for noninvasive positive pressure ventilation.
Such geographic variability suggests there is an implementation gap in patients with chronic obstructive pulmonary disease transitioning from hospital to home.
A recent review of 30-day readmission for patients with chronic obstructive pulmonary disease found significant differences in readmission rates in US hospitals, suggesting that there are differences in quality of care.
To our knowledge, there are no prior reports of “real-world” studies of national-level data on positive airway pressure therapy and subsequent hospitalization risk in patients with chronic obstructive pulmonary disease.
Study Limitations
A 2013 Cochrane review of noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease recommended that future research should focus on ventilator settings, training, and length of ventilation among other variables.
Although our study is responsive to the call for comparative effectiveness of various positive airway pressure therapy settings, such as continuous positive airway pressure, bilevel-positive airway pressure, and home ventilators with noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease, we should be cautious in comparing across the various treatment groups despite the efforts to adjust for indication bias through the use of propensity scores and matched medication only (control) groups. Our study has other limitations, such as the use of administrative data and not performance of chart reviews, and the retrospective nature of the analyses. Nevertheless, such data support the need for clinical trials to test positive airway pressure therapy for reduction of hospitalizations and thereby improvement of health-related quality of life in patients with chronic obstructive pulmonary disease. In a single-center retrospective cohort study of a quality-improvement initiative, we recently showed that a multifaceted intervention that involved initiation of noninvasive positive pressure ventilation, respiratory therapist–led care, medication reconciliation, appropriate oxygen therapy initiation, and patient education was associated with a similar and significant (97%) reduction in rehospitalization.
In a prior study, hospital admissions significantly worsened the health-related quality of life of patients with chronic obstructive pulmonary disease.
We believe that our current study of the association between positive airway pressure therapy and reductions in hospitalization could translate into significant and meaningful improvements in health-related quality of life of patients with chronic obstructive pulmonary disease if confirmed by prospective randomized controlled trials. For our study, we chose any and chronic obstructive pulmonary disease–related hospitalization as the primary and secondary end points considering that these are the quality metrics that are factored when considering hospital performance and are impactful clinical events.
Moreover, it seems that the reduction in hospitalizations may be greater in patients with comorbidities than without comorbidities, such as sleep-disordered breathing, chronic respiratory failure, and congestive heart failure (Figure 3). Such data are in line with recent observations that sleep-disordered breathing may be an independent risk factor for hospital readmissions.
Exploring novel Medicare readmission risk variables in chronic obstructive pulmonary disease patients at high risk of readmission within 30 days of hospital discharge.
Previous reports had not considered the relation of positive airway pressure devices to hospitalizations in patients with chronic obstructive pulmonary disease.
Our study adds to a developing body of literature that suggests the initiation of positive airway pressure therapy was independently associated with the reduction in hospitalization of patients with chronic obstructive pulmonary disease. Whether this association is causal cannot be determined from our observational data and warrants future intervention studies.
Trends in chronic bronchitis and emphysema. Morbidity and Mortality. American Lung Association Epidemiological and Statistics unit Research and Program Services 2013; Available at: http://www.lung.org/assets/documents/research/copd-trend-report.pdf. Accessed November 23, 2016.
A propensity-matched retrospective analysis to identify predictors of rehospitalization for patients with chronic obstructive pulmonary disease (COPD). C51. Hospitalization and readmission in chronic obstructive pulmonary disease:.
Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.
Exploring novel Medicare readmission risk variables in chronic obstructive pulmonary disease patients at high risk of readmission within 30 days of hospital discharge.
Funding: Funding support and access to Truven Health MarketScan Database were provided by Philips-Respironics, Inc. The funding institution did not have any role in the design, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. SP was supported by National Institutes of Health Grants (HL095799, HL095748, and CA184920) during the preparation and writing of this manuscript. Research reported in this manuscript was partially funded through a Patient-Centered Outcomes Research Institute Award (IHS-1306-02505, EAIN #3394-UoA, and PPRND-1507-31666). The statements in this article are solely the responsibility of the authors and do not necessarily represent the views of Patient-Centered Outcomes Research Institute, its Board of Governors, or Methodology Committee.
Conflict of Interest: SP reports grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (HL095799 and HL095748), grants from Patient-Centered Outcomes Research Institute (IHS-1306-2505, EAIN #3394-UoA, and PPRND-1507-31666), grants from the US Department of Defense, grants from the NIH (National Cancer Institute; R21CA184920), grants from Johrei Institute, personal fees from American Academy of Sleep Medicine, personal fees from American College of Chest Physicians, nonfinancial support from National Center for Sleep Disorders Research of the NIH (National Heart, Lung, and Blood Institute), personal fees from UpToDate Inc, Philips-Respironics, Inc, and Vaopotherm, Inc, and grants from Younes Sleep Technologies, Ltd, Niveus Medical Inc, and Philips-Respironics, Inc, outside the submitted work. SP also has a patent: UA 14-018 U.S.S.N. 61/884,654; PTAS 502570970 (Home Breathing Device). The conflicts including the patent are unrelated to the topic of this article.
Authorship: All authors had access to the data and played a role in writing this manuscript.
The abstract from this article has been accepted as late breaking abstract at the American Thoracic Society 2016 conference, May 13-18, 2016, San Francisco, California.
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