POSITIVE AIRWAY PRESSURE THERAPIES AND HOSPITALIZATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Abstract

Background

Hospitalization of patients with chronic obstructive pulmonary disease (COPD) places a huge healthcare burden. Positive airway pressure (PAP) therapy is sometimes used in COPD patients, but the possible impact on hospitalization risk remains controversial. We studied the hospitalization risk of COPD patients before and after initiation of various PAP therapies in a “real-world” bioinformatics study.

Methods

We performed a retrospective analysis of administrative claims data of hospitalizations in patients with COPD who received or did not receive PAP therapy – continuous PAP, bilevel PAP, and non-invasive positive pressure ventilation using a home ventilator (NIPPV).

Results

The vast majority of 1,881,652 patients with COPD (92.5%) were not receiving any form of PAP therapy. Prescription of bilevel-PAP (1.5%), CPAP (5.6%), and NIPPV (<1%) in patients with COPD demonstrated geographic, sex, and age-related variability. After adjusting for confounders and propensity score, NIPPV (Odds ratio [OR] 0.19 (95% confidence interval [95%CI] 0.13, 0.27)), bilevel PAP (OR 0.42; 95%CI 0.39, 0.45) and CPAP (OR 0.70; 95%CI 0.67, 0.72) were individually associated with lower hospitalization risk in the six months post-treatment when compared with the six months pre-treatment but not when compared with the baseline period between 12 and six months prior to treatment initiation. Stratified analysis suggests that comorbid sleep-disordered breathing, chronic respiratory failure, heart failure, and age < 65 years were associated with greater benefits from PAP therapy.

Conclusion

Initiation of PAP therapy was associated with reduction in hospitalization among patients with COPD but the causality needs to be determined by randomized controlled trials.

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States^1,2. Nearly 12.7 million U.S. adults were estimated to have COPD 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^3,4. The 30-day readmission rate for re-hospitalization of COPD patients is very high and ranges from 20 to 39%^5–7. In an effort to reduce hospitalization in patients with COPD, Medicare currently penalizes hospitals for 30-day readmission of patients with COPD^8,9. Although various medication-based strategies are being developed to reduce hospitalization in patients with COPD, there is an expressed need for studies to evaluate different and non-medication approaches¹⁰.

Observational studies from a multi-center European study and a single-center US study suggest that positive airway pressure (PAP) therapy treatments -- such as continuous positive airway pressure therapy (CPAP) or non-invasive positive pressure ventilation delivered by home ventilators (NIPPV) -- are associated with lower hospitalizations in patients with COPD^11,12. Moreover, in two European randomized controlled trials, bilevel positive airway pressure therapy (bilevel PAP) has been shown to reduce mortality in stable severe COPD patients but not hospitalizations^13,14. Consequently, it is unclear as to whether PAP therapy is an effective intervention that can reduce hospitalization in patients with COPD in the U.S.¹⁵.

We aimed to study the hospitalization risk of COPD patients before and after initiation of various PAP 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 trials¹⁶.

METHODS

Study Design and Population

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 two COPD-related claims (≥ 1 day apart) during this time period were included. COPD-related claims were defined using the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes (e-Table 1). Individuals with claims for a Bilevel PAP, CPAP, or NIPPV device during this time period based upon Current Procedural Terminology (CPT) codes (e-Table 2) were included if they were > 40 years of age 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. Additionally, “medication only” (control) groups who did not receive any form of PAP therapy were identified for each of the three treatment groups. The index date for each control was defined as a date of a COPD-related claim. The medication only groups were frequency matched for similar healthcare utilization, i.e., similar median number of COPD claims in the previous 12 months of the index date as compared to 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 based on three time periods referenced to the index date: The first time period (“baseline”) occurred −360 days to −181 days; the “pre-treatment” 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 COPD-related hospitalization was defined as any hospitalization with a primary diagnosis of COPD.

Covariates and propensity score

Potential confounders that were considered include demographics, co-morbidities, and COPD-related prescriptions. Demographics included age, sex, region (Northeast, Midwest, South, West), and insurance type at the index date (Table 1). Twenty-two common co-morbidities (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. In order to account for baseline characteristics that may have influenced the prescription of PAP device, a propensity score was developed using sleep-disordered breathing (SDB), chronic respiratory failure, and restrictive thoracic disorder to predict treatment assignment (e-Table 3).

Table 1.

Patient Characteristics

	BILEVEL- PAP N=9,156	CPAP N=39,385	NIPPV N=315	p- value*	No PAP treatment N=464,684	p-value†
	N (%)
Age Category‡				<0.001		<0.001
40–49	688 (7.5%)	4,805 (12.2%)	15 (4.8%)		57,053 (12.3%)
50–59	2,248 (24.6%)	11,719 (29.8%)	57 (18.1%)		117,272 (25.2%)
60–69	3,150 (34.4%)	12,665 (32.2%)	95 (30.2%)		120,994 (26.0%)
70–79	2,161 (23.6%)	7,515 (19.1%)	102 (32.4%)		90,270 (19.4%)
80+	909 (9.9%)	2,681 (6.8%)	46 (14.6%)		79,095 (17.0%)
Sex				<0.001		<0.001
Males	5,880 (64.2%)	21,617 (54.9%)	161 (51.1%)		204,828 (44.1%)
Females	3,276 (35.8%)	17,768 (45.1%)	154 (48.9%)		259,856 (55.9%)
Health Plan   Type				<0.001		<0.001
Comprehensive	2,741 (29.9%)	9,147 (23.2%)	118 (37.5%)		134,647 (29.0%)
EPO§	50 (0.6%)	244 (0.6%)	0 (0.0%)		3,487 (0.8%)
POS‖	556 (6.1%)	2,959 (7.5%)	21 (6.7%)		27,332 (5.9%)
CDHP**	181 (2.0%)	1,063 (2.7%)	9 (2.9%)		10,505 (2.3%)
HDHP††	76 (0.8%)	475 (1.2%)	2 (0.6%)		5,138 (1.1%)
PPO‡‡	5,552 (60.6%)	25,497 (64.7%)	165 (52.4%)		283,575 (61.0%)
Region				<0.001		<0.001
Northeast§§	1,448 (15.8%)	5,667 (14.4%)	32 (10.2%)		87,022 (18.7%)
Midwest‖‖	3,399 (37.1%)	13,135 (33.4%)	55 (17.5%)		153,314 (33.0%)
South***	3,163 (34.6%)	15,187 (38.6%)	186 (59.1%)		162,447 (35.0%)
West†††	1,073 (11.7%)	5,002 (12.7%)	40 (12.7%)		57,915 (12.5%)
Missing	73 (0.8%)	394 (1.0%)	2 (0.6%)		3,986 (0.9%)

^*p-value from χ² test for difference across treatments

^†p-value from χ² test for difference between treated vs. non-treated groups

^‡Age on first claim for device;

^§EPO- Exclusive Provider Organization;

^‖POS- Non-Capitated Point-of-Service;

^**CDHP- Consumer Driven Health Plan;

^††HDHP- High Deductible Health Plan;

^‡‡PPO;

^§§Mid Atlantic, New England;

^‖‖East North Central, West North Central;

^***East South Central, South Atlantic, West South Central;

^†††Mountain, Pacific.

Table 2.

Baseline co-morbidities

	BILEVEL-PAP N=9,156	CPAP N=39,385	NIPPV N=315	p- value*	No PAP treatment N=464,684	p- value†
	N (%)
Cancers
Cancer (breast, colorectal, lung, and prostate)	573 (6.3%)	2,315 (5.9%)	30 (9.5%)	0.011	31,827 (6.9%)	<0.001
Lung cancer	149 (1.6%)	484 (1.2%)	12 (3.8%)	<0.001	8,438 (1.8%)	<0.001
Cardiovascular
Atrial fibrillation	1,660 (18.1%)	4,454 (11.3%)	65 (20.6%)	<0.001	39,079 (8.4%)	<0.001
Congestive heart failure	2,567 (28.0%)	4,956 (12.6%)	110 (34.9%)	<0.001	43,073 (9.3%)	<0.001
Coronary heart disease	2,766 (30.2%)	9,302 (23.6%)	104 (33.0%)	<0.001	82,282 (17.7%)	<0.001
Hypercholesterolemia	1,186 (13.0%)	5,061 (12.9%)	35 (11.1%)	0.627	48,608 (10.5%)	<0.001
Hyperlipidemia	2,929 (32.0%)	12,741 (32.4%)	75 (23.8%)	<0.001	121, 483 (26.1%)	<0.001
Hypertension	5,858 (64.0%)	23,413 (59.5%)	195 (61.9%)	<0.001	228,094 (49.1%)	<0.001
Ischemic heart disease	547 (6.0%)	1,637 (4.2%)	15 (4.8%)	<0.001	14,683 (3.2%)	<0.001
Chronic kidney disease	1,794 (19.6%)	4,496 (11.4%)	66 (21.0%)	<0.001	43,007 (9.3%)	<0.001
Cerebrovascular
Stroke	917 (10.0%)	3,074 (7.8%)	33 (10.5%)	<0.001	34,541 (7.4%)	<0.001
Mental
Alzheimer’s disease and related dementia	138 (1.5%)	382 (1.0%)	7 (2.2%)	<0.001	10,274 (2.2%)	<0.001
Anxiety disorders	682 (7.5%)	2,960 (7.5%)	48 (15.2%)	<0.001	30,748 (6.6%)	<0.001
Bipolar disorder (manic depression)	121 (1.3%)	443 (1.1%)	5 (1.6%)	<0.001	3,636 (0.8%)	<0.001
Depression	937 (10.2%)	3,851 (9.8%)	48 (15.2%)	<0.001	32,616 (7.0%)	<0.001
Schizophrenia and other psychotic disorders	26 (0.3%)	60 (0.2%)	0 (0%)	0.019	786 (0.2%)	0.725
Metabolic
Diabetes	3,859 (42.2%)	13,406 (34.04%)	94 (29.8%)	<0.001	95,552 (20.6%)	<0.001
Musculoskeletal/Connective Tissue
Osteoporosis	213 (2.3%)	746 (1.9%)	22 (7.0%)	<0.001	15,073 (3.2%)	<0.001
Rheumatoid arthritis and related disease	298 (3.3%)	1,168 (3.0%)	7 (2.2%)	<0.001	11,378 (2.5%)	<0.001
Osteoarthritis	4,899 (17.8%)	19,680 (16.7%)	29 (9.2%)	<0.001	60,829 (13.1%)	<0.001
Respiratory
Asthma	1,889 (20.6%)	8,734 (22.3%)	69 (21.9%)	0.006	65,794 (14.2%)	<0.001
Sleep
Sleep disordered breathing	5,410 (59.1%)	22,616 (57.4%)	64 (20.3%)	<0.001	14,840 (3.2%)	<0.001
Chronic respiratory failure	551 (6.0%)	448 (1.1%)	89 (28.3%)	<0.001	1,655 (0.4%)	<0.001
Hypoxemia	1,512 (16.5%)	3,005 (7.6%)	95 (30.2%)	<0.001	17,664 (3.8%)	<0.001
Insomnia	727 (7.9%)	3,854 (9.8%)	23 (7.3%)	<0.001	16,049 (3.5%)	<0.001
Morbid Obesity	1,030 (11.3%)	2,870 (7.3%)	22 (7.0%)	<0.001	7,179 (1.5%)	<0.001
Restrictive thoracic disorder	307 (3.4%)	469 (1.2%)	32 (10.2%)	<0.001	5,771 (1.2%)	<0.001
Acute Respiratory Failure	2,019 (22.1%)	2,484 (6.3%)	178 (56.5%)	<0.001	21,316 (4.6%)	<0.001

^*p-value from Chi-2 test for difference across treatments

^†p-value from Chi-2 test for difference between treated vs. non-treated groups

Table 3.

Association between Various PAP therapies and Hospitalizations with Matched Medication only (control) Groups

	Any Hospitalization*		COPD-Related Hospitalization*
	N	OR (95% CI), p	N	OR (95% CI), p
BILEVEL-PAP	298,792		298,792
Treatment Group	9,156	0.40 (0.37, 0.43), <0.001	9,156	0.45 (0.38, 0.52), <0.001
Medication only (control) Group	289,636	0.47 (0.46, 0.48), <0.001	289,636	0.39 (0.38, 0.40), <0.001
CPAP	504,069		504,069
Treatment Group	39,385	0.67 (0.65, 0.70), <0.001	39,385	0.52 (0.47, 0.59), <0.001
Medication only (control) Group	464,684	0.51 (0.51, 0.52), <0.001	464,684	0.36 (0.35, 0.37), <0.001
NIPPV	80,952		80,952
Treatment Group	315	0.21 (0.15, 0.30), <0.001	315	0.29 (0.18, 0.47), <0.001
Medication only (control) Group	80,637	0.59 (0.58, 0.60), <0.001	80,637	0.58 (0.56, 0.60), <0.001

^*Adjusted for the propensity score, age, sex, region, insurance type, acute respiratory failure, Alzheimer’s and related dementia, anxiety or bipolar disorder, asthma, atrial fibrillation, chronic kidney disease, coronary heart disease, congestive heart failure, depression, diabetes, hypercholesterolemia or hyperlipidemia, hypertension, hypoxemia, insomnia, ischemic heart disease, lung cancer, morbid obesity, osteoarthritis, osteoporosis or rheumatoid arthritis and related disease, schizophrenia and other psychotic disorders, stroke, SABA or LABA, SAMA or LAMA, SABA+ACS, methylxanthines, ICS, ICS+LABA, oral prednisone, smoking cessation, and oxygen

Statistical analysis

Differences in baseline characteristics and co-morbidities across PAP groups and between PAP treated versus medication only groups were assessed using the χ² 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 two main models of interest investigated the relationship between the treatment devices and any hospitalization (primary end-point) or COPD-related hospitalizations (secondary end-point). Additionally, we examined the effect of each device as compared to their matched medication-only control group for any and COPD-related hospitalizations, for a total of six additional models after adjusting for various covariates included the propensity score. Linear contrasts were used to test for differences in the hospitalization risk in the six months post treatment (period 3) when compared with the six months pre-treatment (period 2) across PAP 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 were additionally stratified by subjects with and without sleep disordered breathing, congestive heart failure, age < or > 65 years, and chronic respiratory failure. Statistical analyses were performed with Stata version 14.0 (Statacorp LP, College Station, TX, USA).

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 two COPD-related claims (≥ 1day apart) of whom 28,774 enrollees were initiated on Bilevel-PAP therapy; 112,119 enrollees on CPAP therapy; and 1,011 enrollees on NIPPV therapy. After excluding subjects who did not meet the continuous enrollment or age criteria, there were a total of 9,156 subjects on Bilevel-PAP, 39,385 subjects on CPAP, and 315 subjects on NIPPV who were included in the analysis. The medication only groups that were generated after matching for the median COPD-related claims were as follows: There were 289,636 subjects in the matched Bilevel-PAP control group with median number of 5 (inter-quartile range [IQR] of 3, 10) COPD claims/year that was comparable to COPD claims/year for Bilevel-PAP treated group (median 5; IQR 1, 17). Similarly, the COPD claims/year for the 464,684 subjects in the matched CPAP control group (median 3; IQR 2, 5) were comparable to that in the CPAP treated group (median 2; IQR 0, 8). Also, the COPD claims/year for the 80,637 subjects in the matched NIPPV control group (median 27; IQR 18, 37) were comparable to that in the NIPPV treated group (median 27; IQR 7, 54).

Figure 1.

Flow chart of patients with chronic obstructive pulmonary disease (COPD) who received various forms of positive airway pressure (PAP) therapy such as Bilevel-PAP therapy, continuous positive airway pressure (CPAP) therapy and home ventilators that delivered non-invasive positive pressure ventilation (NIPPV) therapy. Enrollees with hospital admission discharge status of “died” that occurred within 6 months of treatment initiation were as follows: Bilevel-PAP (N=108 [0.39%]), CPAP (N=106 [0.1%]), NIPPV (N=16 [1.69%]), Non-treated frequency-matched controls for CPAP (N=672 [0.05%]), frequency-matched controls for Bilevel-PAP (N=3,192 [1.1%]), frequency-matched controls for NIPPV (N=1,502 [1.86%]).

The vast majority of patients with COPD (92.5%) were not receiving any form of PAP therapy (Figure 1) with a significant minority receiving PAP therapy: CPAP (5.6%), bilevel-PAP (1.5%), and NIPPV therapy (<1%). There was significant geographical, sex, and age-related variability with regards to the type of PAP therapy prescribed to patients with COPD (e-Figure 1 and Table 1). Patients receiving NIPPV were older and resided in the southern region than patients who received bilevel-PAP or CPAP therapy (Table 1).

Comorbidities are shown by each treatment in Table 2 and the corresponding ICD9 codes are available in e-Table 4. In general, there were more co-morbidities in the patients receiving NIPPV than those receiving Bilevel-PAP or CPAP therapy (Table 2) and cardiovascular disease was the most common comorbidity for all three groups of patients^17,18. In particular, acute and chronic respiratory failure were more common in patients receiving NIPPV than in the other two groups. Prescription of any medication for COPD grouped by drug mechanism of action was determined (e-Table 5). 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 NIPPV therapy in the 12 months prior to NIPPV being issued. Such medication prescription data combined with worse comorbidities and other baseline characteristics (such as age) in the NIPPV group indicates the possibility of confounding by indication for the level of support rendered by the type of PAP therapy with progressively greater degree of respiratory muscle unloading accomplished by CPAP, bilevel PAP and NIPPV 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 three time periods in e-Figure 2 for any hospitalization and for COPD-related hospitalization (e-Table 6). For all periods, crude hospitalization rates were highest in the NIPPV group. For all treatment groups, hospitalization rates peaked in the pre-treatment period and in the post-treatment period the hospitalizations returned to levels during the baseline period. After adjusting for various covariates and propensity score, PAP therapy was associated with the reduction of any hospitalizations or COPD-related hospitalizations (Figure 2) in the post-treatment period when compared to the pre-treatment period (e-Table 7). For any hospitalizations, the observed reduction was greater in patients receiving NIPPV than those receiving CPAP (p<0.001) or bilevel PAP therapy (p<0.001). For COPD-related hospitalizations, the observed reductions in patients receiving NIPPV therapy were greater than those receiving CPAP therapy (p=0.01).

Figure 2.

Longitudinal associations (adjusted odds ratios) for any and chronic obstructive pulmonary disease (COPD) -related hospitalization in patients with COPD comparing 6 months post device treatment (+1 to +180 days) to 6 months pre device treatment (−180 days to 0 days) periods.

Considering that PAP therapy initiation in an ambulatory setting may be different than that in recently hospitalized patients, we stratified the data by whether the PAP device was initiated within ±12 days of a hospitalization (e-Tables 8 and 9). Such stratification did not materially change the results. Crude hospitalization rates and adjusted odds ratios for both the PAP treatment and corresponding matched medication only groups are provided in e-Table 10 and Table 3, respectively. In general, patients receiving PAP treatment suffered greater hospitalizations in the pre-treatment period than in the post-treatment period (e-Figure 2; e-Table 6; P<0.0001). A similar trend was seen for medication-only group, which had a higher hospitalization risk in the six months preceding the index date as compared with the six months following the index date. Also, stratification by the presence or absence of comorbid sleep disordered breathing did not appear to materially modify results (e-Tables 11 and 12) and suggest that comorbid sleep disordered breathing in patients with COPD may be associated with greater reduction in hospitalization. In patients with COPD and comorbid sleep disordered breathing, NIPPV appeared to be associated with greater reductions in any- and in COPD-related hospitalizations (e-Table 12). Similarly, comorbid chronic respiratory failure (e-tables 13 and 14), age < 65 years (e-tables 15 and 16), and comorbid congestive heart failure (e-tables 17 and 18) were associated with greater reduction in hospitalizations in patients with COPD (figure 3).

Figure 3.

Longitudinal associations (adjusted odds ratios) for any and chronic obstructive pulmonary disease (COPD) -related hospitalization in patients with COPD comparing 6 months post device treatment (+1 to +180 days) to 6 months pre device treatment (−180 days to 0 days) periods after stratification by patients with and without sleep-disordered breathing (SDB; left upper panel); with and without chronic respiratory failure (right upper panel); age < 65 or > 65 years (left lower panel) and with and without heart failure (right lower panel).

DISCUSSION

In this “real-world” study derived from administrative claims data, PAP therapy was generally prescribed to older COPD patients with greater comorbidities and greater health care utilization with significant geographical variability in such practice. Among COPD patients who received PAP therapy, initiation of treatment was associated with a reduction in hospitalization risk in the subsequent six months as compared with the six months that preceded PAP initiation and this improvement was particularly strong in the NIPPV 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 PAP therapy or a more powerful PAP 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 six-month period preceding initiation of PAP therapy, suggesting that the prescription of the PAP device may have been a component of a broader management strategy and may have been accompanied by other types of therapeutic interventions possibly impacting risk for subsequent hospitalizations. This possibility is also supported by the observation of similar improvements in hospitalization risk occurring among medication only (control) groups despite these patients not receiving any PAP therapy. Nevertheless, NIPPV 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 PAP therapy devices such as NIPPV, we cannot determine from our observational data whether these effects are actually related to the PAP therapy or any other interventions and/or factors that took place at the time of PAP initiation and whether the baseline differences in comorbidities across the three treatment groups may have contributed to some of the observed effects. Lastly, 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 systematic difference in such loss of insurance coverage in one 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 PAP therapies in patients with COPD and provide preliminary data for performing sample size estimations.

Initiation of bilevel-PAP therapy in patients with severe stable COPD with significant hypercapnia (PaCO₂ > 52 mmHg) has been shown to reduce mortality, but have no effect on hospitalization¹³. There is, however, prospective observational data from a large European study that CPAP therapy is associated with reduction of a composite outcome of hospitalization and mortality in patients with COPD and coexistent sleep disordered breathing¹¹. However, the use of any PAP therapy in patients with COPD regardless of presence of sleep disordered breathing is uncommon in the U.S. with a majority of patients with COPD (92.5%) not receiving any form of PAP therapy. In contrast, recent data suggests that 30% of European patients with COPD received prescription for NIPPV¹⁹. Such geographic variability suggests that an implementation gap in COPD patients transitioning from hospital to home²⁰. A recent review of 30-day readmission for patients with COPD found significant differences in readmission rates in US hospitals suggesting that there are differences in quality of care²¹. In the same review, PAP therapy was not considered for risk-adjustment²¹. To our knowledge, there are no prior reports of “real-world” studies of national level data on PAP therapy and subsequent hospitalization risk in patients with COPD.

A 2013 Cochrane review of NIPPV in patients with COPD recommended that future research should focus on ventilator settings, training and length of ventilation amongst other variables.²² Whilst our study is responsive to the call for comparative-effectiveness of various PAP therapy settings such as CPAP, bilevel-PAP and home ventilators with NIPPV in patients with COPD, 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 PAP therapy for reduction of hospitalizations and thereby improvement of health-related quality of life in patients with COPD. Recently, we have shown that, in a single-center retrospective cohort study of a quality improvement initiative, a multi-faceted intervention that involved initiation of NIPPV, respiratory therapist led care, medication reconciliation, appropriate oxygen therapy initiation, and patient education was associated with a similar and significant (97%) reduction in rehospitalization¹². In a prior study, hospital admissions significantly worsened the health-related quality of life of patients with COPD²³. We believe that our current study of the association between PAP therapy and reductions in hospitalization could translate into significant and meaningful improvements in health-related quality of life of patients with COPD if confirmed by prospective randomized controlled trials. For our study, we chose any- and COPD-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^9,21,24. Moreover, it appears that the reduction in hospitalizations may be greater in patients with than without comorbidities such as sleep disordered breathing, chronic respiratory failure, and congestive heart failure (Figure 3). Such data is in line with recent observations that sleep disordered breathing may be an independent risk factor for hospital readmissions²⁵. Previous reports had not considered the relation of PAP devices to hospitalizations in patients with COPD.²¹ In sum, our study adds to a developing body of literature that suggests that initiation of PAP therapy was independently associated with the reduction in hospitalization of patients with COPD. Whether this association is causal cannot be determined from our observational data and warrants future intervention studies.

Clinical Significance.

• Initiation of positive airway pressure therapy was associated with reduction in hospitalization among patients with chronic obstructive pulmonary disease.

• Only 7.5% of 1,881,652 patients with chronic obstructive pulmonary disease were receiving some form of positive airway pressure therapy.

• Comorbid sleep-disordered breathing and chronic respiratory failure were associated with greater benefits from positive airway pressure therapy.

Abbreviation list

ACS

Anticholinergic bronchodilators

Bilevel PAP

Bilevel positive airway pressure therapy

CI

Confidence interval

COPD

Chronic obstructive pulmonary disease

CPAP

Continuous positive airway pressure

CPT

Current Procedural Terminology

ICD-9

International Classification of Diseases, Ninth Revision

ICS

Inhaled corticosteroids

IQR

Inter-quartile range

LABA

Long acting beta agonists

LAMA

Long acting muscarinic antagonists

NIPPV

Non-invasive positive pressure ventilation delivered by home-ventilators

OR

Odds ratio

PAP

Positive airway pressure

SABA

short acting beta agonists

SAMA

short acting muscarinic antagonists