Abstract
Objective: There are currently 39 FDA-approved metered-dose (MDI) or dry-powder inhalers (DPI) on the US market. Most are high cost with significantly more drug in the device than needed for a typical average length of stay in acute care hospitals, which leads to significant waste. The objective was to assess the financial impact and chronic obstructive pulmonary disease (COPD) outcomes of a comprehensive inhaler to nebulization protocol implemented in a large multi-state US health system.
Methods: The retrospective study evaluated respiratory drug costs at 28 hospitals in the health system after a phased implementation of the automatic inhaler to nebulization protocol. Purchasing data was collected for all respiratory medications impacted by the protocol for the twelve months preceding as well as the two subsequent twelve-month periods following implementation at each facility. COPD length of stay (LOS) and 30 day readmissions were also reviewed. An attempt was made to evaluate the impact on respiratory therapy (RT) department workload.
Results: Compared to pre-implementation, system-wide drug expenditures declined $1,561,011 (38.5%) and $1,646,411 (40.6%) in post-implementation year 1 (PY1) and post-implementation year 2 (PY2), respectively. COPD LOS and 30 day readmissions were not adversely affected and remained relatively stable in comparative periods. Objective impact on RT productivity and labor statistics was not ascertained due to complicated variables and multiple service lines.
Conclusions: In an era of increased drug costs incurred by hospitals, a comprehensive inhaler to nebulization protocol significantly decreased costs without incurring any negative observed trends in COPD LOS or readmissions.
Introduction
Patients with respiratory conditions including chronic obstructive pulmonary disease (COPD) and asthma are routinely treated with metered dose inhalers (MDI) and/or nebulized medications in the outpatient setting depending on insurance coverage and severity of disease. When patients are hospitalized this therapy is typically continued. However, there are currently 39 different inhalers on the US market () making it unrealistic to expect US hospitals to carry the majority of these from a cost-effective formulary standpoint. Unfortunately, drug price inflation continues to increase at an alarming rate and can incur a significant burden on both patients and hospitals. A recent report from NORC at the University of Chicago commissioned by the American Hospital Association and Federation of American Hospitals suggests that hospital inpatient drug spending increased an average of 23.4% (38.7% on a per admission basis) between 2013 and 2015. Over 90% of hospitals reported that inpatient drug price inflation incurred a moderate to severe effect on their ability to manage costs especially in the era of bundled paymentsCitation1. A 2018 GoodRx analysis of consumer cash prices for inhalers suggests an inflation rate of 35% since 2013Citation2, but specifics on whether health systems are absorbing similar increases in the respiratory medication space is not as well known. To understand this more clearly an internal evaluation of our health system’s group purchasing organization (GPO) Premier contracted prices for the 27 most common inhalers and strengths historically utilized including fluticasone/salmeterol (Advair Diskus/HFA), ipratropium (Atrovent HFA), ipratropium/albuterol (Combivent Respimat), fluticasone (Flovent Diskus/HFA), albuterol (ProAir HFA, Proventil HFA, Ventolin HFA), budesonide (Pulmicort Flexhaler), beclomethasone (Qvar Redihaler HFA), salmeterol (Serevent Diskus), budesonide/formoterol (Symbicort HFA) and tiotropium (Spiriva Handihaler) revealed a similar combined increase of 28.5% from 2014 to 2018.
Table 1. Current FDA-approved inhalers available on the US marketTable Footnotea.
Inhalers present a unique challenge for hospitals in that they are widely used for both exacerbations and maintenance of asthmatic patients and those with chronic obstructive pulmonary disease (COPD). Despite some recent improvements in the availability of institutional size inhalers, the vast majority still contain significantly more doses than are needed for a typical average LOS of 4 to 6 days for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD)Citation3,Citation4. Unfortunately, as illustrated by Sakaan et al., this discordance will likely result in significant waste; they found 87% of total doses dispensed of either a metered-dose inhaler (MDI) or dry-powder inhaler (DPI) remained unusedCitation5. A more recent assessment by another health system reported 90% of doses remaining unused, which correlated with the average LOSCitation6. Our own internal evaluation of inhaler waste which was previously reported suggested a similar level of wasted doses (89%) and supports these assessmentsCitation7. We additionally evaluated potential tiotropium (Spiriva Handihaler) waste more specifically since annual system costs exceeded $500,000 for this inhaler alone. It is a 5 day institutional size product and dispensed with only five 18 mcg tiotropium capsules, so waste should be greatly minimized. However, over a 4 month time frame from October 2015 through January 2016, 3,207 of these inhalers were dispensed system-wide with a total of 16,035 doses. Only 9,278 doses were documented on the medication administration record (MAR) as being given to the patients. Based on this, 6,757 doses (42%) should have been sent back to the pharmacy to be wasted. A significant contributor to inhaler waste, which can be difficult to quantify, is the high percentage of lost inhalers that can occur as patients transition from different levels of acuity. These then require subsequent replacement with another potentially high-cost inhaler that will likely only be partially used. A recent evaluation suggested that this could range from 15% to 27% of dispensed inhalersCitation8. The evolution and increasing number of unique inhalers on the market continues to exacerbate this overall issue in acute care. To control costs, preferred contracting and therapeutic substitutions of the majority of inhalers within a specified class can be considered. Our health system, which comprises 29 acute care hospitals (rural, urban and academic) and one behavioral health facility in six US states (Arizona, California, Colorado, Nebraska, Nevada and Wyoming) instituted an automatic therapeutic interchange of all inhaled corticosteroid (ICS) and inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) inhalers to GlaxoSmithKline (GSK)-preferred inhalers (Flovent Diskus/HFA and Advair Diskus/HFA, respectively) in 2012 to achieve an estimated $500,000 annual savings on inhaler costs. This was also successful in significantly reducing the number of inhalers stocked on formulary; however, lost inhalers and wasted doses were still very prevalent as stated previously despite being able to increasingly utilize the institutional size inhalers provided by GSK. Another option that many hospitals have entertained to curb inhaler costs and minimize waste is by instituting common canister (CC) protocols and although these can be successful they do require close attention to detail as it relates to infection control issues as well as associated processes to be sure certain patient populations are excludedCitation7. Despite implementing the system-approved preferred inhaler therapeutic interchange in 2012, three urban community hospitals in our health system still found inhaler costs and waste to be unacceptable. As a result, in 2013 and 2014 a CC protocol utilizing fluticasone/salmeterol (Advair HFA), fluticasone (Flovent HFA), albuterol HFA (Ventolin, Proventil), ipratropium/albuterol (Combivent MDI & Respimat) and ipratropium (Atrovent HFA) inhalers was implemented as part of their local individual facility-based optimization projects. The primary exclusions were intensive care units (ICUs) and isolation patients (i.e. positive culture results). On annual follow-up, the results showed a 51% to 81% reduction in inhaler purchases depending on the campus. Although the respiratory therapists (RTs) did not administer patient-specific inhalers at those campuses prior to implementing this protocol, it was reported that there was no increase in RT labor despite shifting this role away from nursing. Variations in the percentage reduction in inhaler purchases were thought to be related to the degree of protocol exclusion patients served at each campus, which is an important consideration. Common or shared canister protocols will not capture every patient, so depending on the populations served hospitals choosing this methodology may potentially still be dispensing significant numbers of patient-specific inhalers.
In aggregate our health system purchased approximately 54,000 inhalers with a total expenditure of $3.47 million in 2014. As a result, in 2015 there was a subsequent initiative to standardize delivery and reduce variations, waste and costs of respiratory medications at all campuses. To achieve this, a multi-disciplinary team was developed, which included representatives from pharmacy, respiratory therapy, informatics, infection prevention, supply chain, finance, clinical education, project management, process engineering and executive administration. Secondary to the perceived success of the common canister implementations, the team initially recommended considering this for all campuses in the system with estimated drug savings of $833,000. However, due to the concerns with infection control risks accompanying this method of drug delivery, the system pulmonary and infectious disease clinical consensus groups (CCGs) would not support approval as a system standardCitation7. As a result, the interdisciplinary team evaluated the alternative option of implementing an inhaler to nebulization protocol.
The American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology considers devices used for the delivery of bronchodilators to be equally efficacious if used properly and nebulized delivery of medications in the acute care setting is already an accepted and widespread practice in the USCitation9. Due to the significant number of inhalers on the market which require various techniques and skill sets, it is also recognized that inhalers are often not administered correctly in acute care settingsCitation10,Citation11. There is also increasing evidence that many hospitalized patients may have inadequate peak inspiratory flow rates (PIFRs) to appropriately use the inhalers they have been prescribedCitation12–15. As a result, it is likely worthwhile to assess function before indiscriminately prescribing expensive inhalers, especially in AECOPD. The added advantage of nebulized medications is that the patient can be dispensed and administered only the drug needed while hospitalized. Unit doses can be stocked in medication dispensing systems, such as Pyxis MedStations throughout the hospital negating the issues of lost inhalers during transitions of care.
Although most are poster presentations and abstracts, there have been numerous reports of implementing inhaler to nebulization protocols with success. These have shown significant cost savings, reduction of formulary medications stocked and reduction in the incidence of therapeutic duplications without incurring significant changes in RT labor, COPD LOS or COPD 30 day readmissionsCitation6,Citation8,Citation16–24. Small studies also support similar protocols in mechanically ventilated long-term care and intensive care unit (ICU) patients suggesting no significant changes in ICU LOS, ventilator days, in-hospital mortality or ventilator-associated pneumonia (VAP) ratesCitation25–29.
Protocol implementation
Initial development of the inhaler to nebulization protocol was based on existing unpublished protocols already implemented in other hospitals or health systems that were shared with the team. Due to the fact that there are limited numbers of nebulized medications and doses available on the US market most protocols were similar in dosing transition. It is also recognized that dose-ranging studies converting from inhalers to nebulization (or vice versa) across the spectrum of approved inhalers are not available in AECOPD. The amount of drug a patient receives from inhalers will be heavily influenced by technique and PIFR, so these conversions will always be empirical to a degree. Therefore, protocol development was based heavily on the routine and standard dosing already used by providers in practice. After development of the automatic inhaler to nebulization protocol (), it was approved by the system pulmonary, infectious disease, hospital medicine, and pharmacy and therapeutics (P&T) committees to proceed with implementation. Based on the conversion protocol and utilizing average lengths of stays for respiratory patients in the health system of 4 to 5 days, it was estimated that annual savings of $800,000 to $1.2 million could be achieved assuming the RT department would remain labor neutral. To be conservative, this also assumed that the common canister facilities would achieve no further decrease in drug expenditures (due to the complexities in predicting potential savings) and did not factor in potential savings for two newly acquired academic medical centers which had not yet been converted from EPIC to Cerner, the latter being the primary electronic health record (EHR) for the health system.
Table 2. Inhaler to nebulization protocol.
Due to the wide variance of acute care facilities in the health system in terms of size, location and populations served, it was important to understand the variances that may exist. The author’s institution shares the campus with the only dedicated children’s hospital who had recently implemented a system asthma initiative utilizing inhalers as an effort to reduce pediatric asthma readmissions. The primary target of this initiative was to utilize albuterol HFA rescue inhalers including in the emergency department (ED) where inexpensive 340B pricing could be utilized. To avoid impacting this initiative, pediatrics was excluded from the protocol system-wide. The one designated behavioral health facility was determined to not primarily serve respiratory patients and as a result did not have a significant annual inhaler spend. It also had longer average lengths of stay with the psychiatric population in general, which resulted in diminished cost saving estimates this protocol could offer. Additionally, three of the acute care hospitals also were determined to have designated inpatient psychiatric units and there was voiced concern that increased use of nebulization (neb) tubing in this population could theoretically increase the risk of patient self-harm. Although the tubing could be removed from the room after treatments to alleviate this risk by an established protocol, it was decided to exclude these specific inpatient psych units and behavioral health hospital from the initiative as well.
Pre-implementation assessment of system-wide neb utilization revealed that delivery of medications by nebulization was a wide-spread common practice with over 1 million neb deliveries annually. Interestingly, 1,037,154 neb deliveries were administered vs. 242,375 inhaler deliveries. This suggests that neb deliveries already accounted for 81.1% of total respiratory drug administrations. This percentage in favor of nebs over inhaler deliveries was consistent for all 26 campuses that data was available for and ranged from 60% as a low to 88.3% as a high. As a result, it was established that no facility needed any up-front technology capital expenditures. Five facilities did not have nebulized arformoterol (Brovana) and/or budesonide on their local formularies which were needed to implement the protocol. Small critical access hospitals in rural communities also communicated that they may lack 24/7 retail pharmacy access when patients were discharged at inopportune times. As a result, impacted facilities were allowed to retain small supplies of inhalers as deemed appropriate to avoid potential readmissions in select situations. The other areas of patient care that required retention of rescue albuterol HFA inhalers were procedural areas, such as the operating rooms (ORs) and interventional radiology/medical imaging where emergent adverse reactions to medications may require prompt administration of bronchodilators.
Of the 28 hospitals planned for implementation, RTs provided both inhaler and neb administration at five, including the three common canister facilities. At all the remainder, nurses provided inhaler administration while RTs provided neb treatments. At nine of the rural critical access facilities, RT coverage is not provided 24 hours per day. As a result, nursing assumes delivery of nebulized medications after normal RT hours, which was a pre-existing standard of practice. Despite widespread acceptance of the initiative by RT departments in general, some concern was voiced about the impact on RT labor. As a result, a phased system implementation plan was developed to allow for gradual feedback from multiple campuses. In addition, all facilities were notified well in advance of their planned go-live dates, so they could gradually reduce inventory of inhalers, update local formularies to match the nebulization protocol, and be sure all staff (i.e. pharmacists, nurses, RTs and providers) were educated and prepared.
The initial pilot (phase 1) at the author’s institution commenced on 5 January 2016. Full system-wide implementation was completed on 1 November 2016 (phase 6) after the more recently acquired academic facilities were converted to the Cerner EHR platform. Due to clinical informatics workload and time constraints, initial implementation of the protocol required pharmacists to manually convert all inhalers ordered by providers using computerized prescriber order entry (CPOE) to the appropriate neb regimen at order verification. The initial pilot facility also implemented the initial Cerner auto-substitution functionality beginning on 21 June 2016 as an informatics pilot. This was subsequently turned on for all existing facilities on 16 August 2016 when 18 additional hospitals (phase 5) implemented the protocol. The purpose of this retrospective study was to analyze a 2 year follow-up of the overall financial impact of this implementation on drug costs as well as any impact on the RT departments. COPD LOS and 30 day readmissions were additionally evaluated.
Methods
Utilizing purchasing data provided by the corporate supply chain director, net inhaler, nebulized medication and supply costs for all facilities was performed for the 12 months immediately prior as well as the two successive 12 month periods immediately post-implementation based on each hospital’s respective go-live dates. A 2 year follow-up was chosen to better understand the consistency of the protocol implementation. Drug costs included all inhalers in as well as the three inhalers formoterol (Foradil), flunisolide (Aerospan), and pirbuterol (Maxair) that have subsequently been taken off the US market. All corporate GSK quarterly market share rebates that the system received for each campus were deducted from their inhaler expenditures for each respective annual time frame. One hospital that is a specialized cancer center was excluded from the calculations after determining that their annual inhaler spend was negligible (i.e. <$200). Although pediatrics was excluded from the original protocol implementation, the children’s medical center was also included in the calculations for the original pilot facility due to combined pharmacy cost centers. Individual quantities of each inhaler purchased in all time frames was analyzed to better understand which inhalers were most prevalent. The following nebulized medication drug costs were also included: albuterol, arformoterol, formoterol, ipratropium, ipratropium–albuterol, levalbuterol and budesonide. Total quantities purchased and annual costs of arformoterol and budesonide nebulized solutions were specifically evaluated since it was anticipated that due to higher unit costs these would make up the majority of post-implementation expenditures. The supply costs included inhaler spacer costs, neb cups, tubing, kits, adapters, masks and mouthpieces needed to administer nebulized medications. Adjusted patient days were determined by utilizing the system finance sharepoint and the case mix index (CMI) for the COPD diagnosis related groups (DRGs) 190, 191, 192 were provided by health system financial analysis consultants. COPD LOS and 30 day readmission data were derived by utilizing the medical information data analysis system (MIDAS) and clinical performance assessment improvement (CPAI) specialists. This study was approved by the Banner Health Research Determination Committee (RDC) and determined to be not research per 45 CFR 46.102.
Results
Pharmacy purchasing data
In 2014, the health system spent a total of $4.25 million dollars on inhalers and nebulized medications combined ($3.47 million inhalers; $783,000 nebulized medications). The aggregate overall expenditure for the immediate 12 month periods preceding phased implementation of each facility was a similar $4,058,006 ($3,165,699 inhalers; $892,307 nebulized medications). This illustrates that inhalers, which only accounted for approximately 18.9% of respiratory drug deliveries pre-implementation incurred about 80% of the total drug costs. Overall drug expenses in post-implementation year 1 (PY1) were dramatically reduced to $2,496,995 ($322,741 inhalers; $2,174,253 nebulized medications), which yielded drug savings of $1,561,011 (38.5% lower). Observationally, despite showing similar percentage reductions to the system average, campuses 1, 2 and 3 () were noted to still have significant inhaler expenditures, which accounted for 77% of the remaining system inhaler usage post-conversion.
Table 3. Annual net drug expenditures and inhaler purchases of each facility: inhalers, nebulized medications and total combined.
At campus 1 ($81,071), this was almost exclusively due to pediatric exclusions at the children’s hospital. Further analysis revealed that $36,849 (45.5%) was secondary to fluticasone/salmeterol (Advair HFA) and fluticasone (Flovent HFA) inhaler use and $42,904 (52.9%) was from albuterol or levalbuterol HFAs. The rescue inhalers accounted for 3356 (87.7%) of the 3826 total inhalers still purchased by the campus. More specifically, 2288 (68.2%) were purchased under less expensive 340B pricing for patients classified as outpatient (emergency room or observation). Since the ICS/LABA and ICS HFA inhalers (n = 462) accounted for a small percentage (12%) of the remaining purchases by number yet accounted for almost 46% of the costs, this instigated a review of our pediatric asthma patients, which showed that the average LOS was less than 2 days. All the ICS/LABA and ICS HFA inhalers used in this population were also 60 or 120 dose inhalers, respectively, which was resulting in significant waste especially considering their higher costs. After discussion with the pediatric pulmonologists at the children’s hospital and further analysis of the pediatric asthma initiative, it was re-determined that the emphasis was being placed on rescue and not maintenance inhalers during inpatient or ED admissions. As a result, at the December 2016 local P&T committee a pediatric-specific inhaler to neb protocol was approved to fold pediatric ICS/LABA and ICS inhalers into the automatic conversion process. However, this was a local campus initiative only, so pharmacists started manually converting these specific pediatric asthma inhalers at order verification beginning late December 2016. Two variations to the pediatric protocol were implemented vs. adult patients: 1) ICS/LABA inhalers convert to budesonide + albuterol (not arformoterol due to limited information regarding nebulized LABA use in pediatric asthma) and 2) if patients were concomitantly receiving systemic corticosteroids (i.e. prednisone, prednisolone, methylprednisolone) then the budesonide neb component would not be ordered as this was considered a therapeutic duplication.
At campus 2, they also serve a pediatric population as well as inpatient psychiatric patients, which were both exclusions. It was additionally determined that when this campus initially implemented the protocol in January 2016 with manual pharmacy conversions, it deviated from the system-approved recommendation by not converting tiotropium (Spiriva Handihalers), which accounted for a significant $76,152 annual spend in the prior year for the facility. Although it is not the case currently with the more recent FDA approvals of glycopyrrolate inhalation solution (Lonhala Magnair) and revefenacin inhalation solution (Yupelri), an FDA-approved nebulized LAMA did not exist on the US market at the time of protocol implementation in early 2016. However, on this campus a small minority of pulmonologists desired retention of a LAMA inhaler, so an alteration in the protocol was made locally to accommodate. In August 2016, however, the health system activated the Cerner EHR functionality to automatically convert all inhalers, including LAMA inhalers. This forced the facility to come in line with the protocol. However, the campus still incurred an expenditure of $32,421 on Spiriva Handihalers in PY1 as a result of the initial deviation.
Secondary to the adjustments mentioned above, overall drug expenditures further declined to $2,411,594 ($208,410 inhalers; $2,203,184 nebulized medications) in post-implementation year 2 (PY2), which was an additional $85,401 (3.4%) reduction vs. PY1. The system realized a larger decrease in drug costs than originally projected, because the two more recently acquired EPIC EHR transition hospitals and three CC facilities were not included or were considered savings neutral in the estimates. However, those facilities decreased drug costs $378,630 and $382,125 combined in PY1 and PY2, respectively. All three CC facilities decreased drug costs after conversion. Campus 4 () achieved the most significant savings since they reported only decreasing inhaler purchases 51% with CC implementation, so they still had significant patient-specific inhaler usage and opportunity to further reduce costs.
Nebulized arformoterol and budesonide expenditures are shown in and make up the majority of the post-implementation spend. Of particular interest is the fact that budesonide nebs alone accounted for approximately 50% of total overall drug expenses in both years post-implementation. Further analysis showed that at only three of the 27 campuses did budesonide nebs account for 30% or less of their total expenditures. At all the rest, budesonide made up 42% to 62% of total campus drug expenditures and this occurrence was consistent in both PY1 and PY2 and transcended small, large, urban, rural and academic hospitals in all six states. One important consideration that needs to be addressed regarding the budesonide expenditure is that 99% of this is from the unit dosed (UD) Nephron Pharmaceuticals product. This is more expensive than alternative generic manufacturers; however, this UD product is individually wrapped and barcoded which greatly maximizes shelf-life vs. non-UD products. It also avoids the need for technicians to manually barcode, so it functions with bar-code medication administration (BCMA) scanners. Having noted our high budesonide expenditures, our system has now been able to re-negotiate contracting with Nephron in 2019 to reduce the price of this product by approximately 44%. Based on annual budesonide expenditures of $1.2 million, this should further reduce annual drug costs by another $500,000 going forward vs. what is being reported for PY1 and PY2 savings.
Table 4. Twelve-month arformoterol and budesonide nebulized medication expenditures: total costs and percentage of total overall system respiratory drug costs.
Inhaler breakdowns are shown in . Pre-implementation ICS, ICS/LABA and LAMA inhalers made up the majority of the overall inhaler purchases and combined were responsible for most of the expenditures incurred due to their higher unit costs. Post-implementation, although the total number of inhalers purchased still appears high at 12,224 in PY1 and 9272 in PY2, 78% (n = 9557) and 87% (n = 8090) were made up by albuterol HFA inhalers, respectively. Additionally, in PY2 5705 (70.5%) of the albuterol HFAs were purchased under 340B pricing for use by patients with outpatient classification (ED/observation) in which the inexpensive pricing can be utilized.
Table 5. Total system net inhaler purchases.
Supply costs
Unlike the medication protocol, standardizing respiratory supplies for neb delivery at all facilities was considered out of scope for the interdisciplinary team as it relates to this implementation since it was determined that all facilities routinely provided nebulized medications. Although no capital expenditures on equipment were required to implement this protocol system-wide, there are numerous variances in terms of what is carried by individual campuses throughout the health system. On review of available system supply chain data, it was noted that use of specific supplies also did not remain static and local campus adjustments were made during the study period that impacted results. For 23 campuses the aggregate expenditures did not vary much per time frames ($349,601 vs. $329,956 vs. $356,628), but for four other facilities the variation was large and deviated significantly from sister facilities of comparable bed size. It is not known whether there are other unknown local campus adjustments in preferred supplies that could have impacted results. As a result, the accuracy of the supply data is called into question despite repeated re-evaluation attempts.
Respiratory therapy impact
It was not possible to determine reliable objective data on the impact on RT labor although, to be clear, no additional labor was granted to RT departments as part of this implementation. Anecdotal feedback from multiple RT directors around the system were positive and there was a feeling that implementation of the protocol did not incur additional labor at either facilities in which RTs provided inhaler administration or those that did not. A consistent theme from campus feedback was that an increase in workload was noticeable in the first 4 hours of the RT shifts, which is understandable since, as per , ∼44% of pre-implementation inhalers were ICS or ICS/LABA maintenance inhalers. These are converted to twice daily scheduled budesonide or budesonide/arformoterol nebs, which are typically provided at 0900/2100 standard administration times. However, the feedback was that this could be addressed by adjusting RT staffing methodology vs. additional labor to handle any increased workloads on the front-end of shifts, which then decline later in the day. A more important consideration communicated by RT directors was that objective productivity and labor data was unreliable as it relates to this protocol, because data does not specifically carve out the impact of nebulization and/or inhalers on their overall work volumes and labor statistics. As an example, is provided to illustrate the vast roles the RT department provides at campus 1 as routine service lines, many of which were not static after implementation. Each service line can be impacted by numerous variables and all of these subsequently affect the department volumes which then impact overall productivity and labor statistics.
Table 6. Potential roles of respiratory therapists.
Patient volumes, respiratory readmissions, length of stay and case mix index
System-wide adjusted patient days were 56,162 (2.8%) higher in PY1 vs. pre-implementation. They were an additional 696 (0.03%) higher in PY2 vs. PY1. Overall system COPD 30 day readmissions declined from 15.7% to 14.7% in PY1 and 14.5% in PY2. Medicare-specific (age 65 and older) COPD 30 day readmissions, which would impact Centers for Medicare & Medicaid Services (CMS) penalties, declined from 15.1% to 13.6% and then rose slightly back to baseline at 15.2%. A slight 0.2 day increase year over year was noted in COPD LOS (); however, in evaluating overall system average LOS trends in both medical–surgical patients and acute Medicare patients during the same time frames, there was a similar increase from 4.3 to 4.7 days and 4.7 to 4.9 days, respectively. COPD-specific patient volumes and CMI were also higher in both years post-implementation ().
Table 7. Comparison of system patient volumes, case mix index, chronic obstructive pulmonary disease readmissions, and length of stay.
As previously mentioned, a pediatric-specific inhaler to nebulization protocol focusing on more expensive ICS and ICS/LABA inhalers was subsequently developed and implemented late December 2016 at the children’s hospital due to remaining high inhaler expenditures. Follow up evaluation of outcomes available in MIDAS for the pediatric asthma population did not show any significant deterioration in LOS or readmissions ().
Table 8. Campus 1 respiratory outcomes data.
Environmental impact and reduction of inhaler hazardous waste expense
Chlorofluorocarbon (CFC) inhalers have been phased out as of the end of 2013 and replaced by hydrofluoroalkane (HFA) inhalers due to the negative impact of CFCs on the ozone layer and global warming. HFAs lack chlorine and do not deplete the ozone; however, they are considered greenhouse gases and still have global warming potentialCitation30. They remain liquefied compressed gas and all package inserts for current FDA-approved HFA inhalers in warn that exposure to temperature above 120 °F may cause bursting. Under the US Environmental Protection Agency’s (EPA’s) Resource Conservation and Recovery Act (RCRA) regulations, to be RCRA compliant canisters that still contain product or gas at disposal must be treated as hazardous waste when their remaining content falls under any of the four D-code characteristics: ignitability (flash point <140 °F), corrosivity, reactivity or toxicityCitation31. Per Stericycle guidance, who manages our medical waste, aerosolized inhalers fall under the classification of ignitability and should be treated as incompatible hazardous waste to be disposed of in black bins. However, on closer evaluation of practice habits of pharmacy personnel it was revealed that most were also disposing of DPIs in these bins, which do not need to be. Quantification of overall disposal costs to the system incurred by inhalers specifically would be inaccurate due to likely variances in this practice, improper disposal in regular trash cans on the floors by non-pharmacy staff and sending inhalers home with patients at discharge despite the fact that the latter practice is not encouraged due to not meeting State Board of Pharmacy requirements necessitating appropriate labeling and counseling of patients. A small analysis of 10 different HFA inhalers with varying amounts of drug left in them weighed an average of 28.3 grams, which yields approximately 16 inhalers per pound of hazardous waste. At the time of protocol implementation it was communicated that our health system paid $2.50/lb to dispose of black bin hazardous waste. Therefore, 1000 aerosolized inhalers would cost approximately $156 to dispose of properly. A consistent stream of partially used inhalers coming back to the pharmacy for disposal is no longer an issue post-implementation. On a relative basis this appears insignificant vs. other savings; however, efforts to minimize pharmaceutical waste are worthwhile.
Discussion
The results of this retrospective, descriptive analysis illustrate the significant drug savings that a large health system can achieve by implementing a comprehensive inhaler to nebulization protocol. Extending the post-implementation evaluation period to two years is beneficial in that it also demonstrates consistency and ability to maintain those cost savings year-over-year especially in an era of current drug price inflation. Patient volumes and CMI for the annual time frames do not suggest that cost reductions were a result of treating less complicated patients. As stated previously, evaluating Premier GPO pricing for common inhalers utilized by our health system showed a 28% increase from 2014 to 2018. A narrower time-frame evaluation from 2017 to 2018 showed the inhaler inflation rate continuing to average 6% annually. The drug expenditure reductions in each of the post-implementation periods are based on actual costs and do not consider what could have been spent in those periods if the health system had retained and used similar quantities of inhalers as prior to the implementation. Other than arformoterol (Brovana), all other standard nebulized medications are generic with multiple manufacturers which holds prices down through competition. Premier GPO pricing evaluation for our health system from first quarter (QTR) 2016 to fourth QTR 2018 showed no price inflation with albuterol, ipratropium, albuterol/ipratropium, levalbuterol and budesonide nebulized medications. Despite being brand name only, as of May 2019 arformoterol (Brovana) has also not experienced a price increase for our health system since July 2017 through effective contracting with the pharmaceutical company. As a result, listed drug expenditure reductions likely underestimate actual drug savings based on the observed dichotomy in price increases noted between inhalers and nebulized medications. Projecting forward, both arformoterol (Brovana) and formoterol (Perforomist) will experience patent expiration in 2021, which should allow for further savings within an all-nebulization model in the US.
Although causality cannot be inferred from this analysis, no observational negative impact on overall system COPD LOS and 30 day readmissions was noted from significantly reducing inhaler usage during admission. Numerous variables can impact LOSCitation33,Citation34. A recent study in COPD Medicare patients reported only 50% of readmissions to be related to respiratory causesCitation35. Factors that may impact readmissions, for example, include comorbidities, severity of illness, discharge destinations to home vs. skilled nursing facilities and socioeconomic statusCitation36,Citation37. Specifics, such as these were outside of the scope of this evaluation.
There can be concern about not providing patient-specific inhalers in the hospital for patient education reasons, but unless most inhalers with varying device techniques are carried on formulary and the institution has routine comprehensive education for all the staff responsible for administering and teaching throughout the hospital stay then this model will still have inherent deficiencies and does not necessarily mean the drug is administered or taught correctlyCitation10,Citation11,Citation38,Citation39. A recent study suggests that a high percentage of pulmonologists may not even have the skill set to teach all the medications they are potentially prescribingCitation40. The other issue that confounds this is the fact that suboptimal PIFRs have been linked to COPD all-cause readmissionsCitation13. The prevalence of low PIFRs at discharge has been reported to be as high as 33%, so more attention to device selection may be prudent as wellCitation12,Citation14,Citation15. Any concern for the occasional individual patient desire to have an inhaler while admitted can be addressed through home medication use policies and procedures that should already be in place since US hospitals cannot carry every FDA-approved drug on the US market across pharmacologic classes. Follow-up with patient relations to assess whether there was any negative impact of this protocol in terms of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys did not reveal any issues. It was reported that there are no specific questions pertaining to inhalers on these surveys. However, it was also reported that in comment sections there had not been any observations of inhaler unavailability being an area of contention with patients.
Additionally, not to undermine the importance of inhaler education, discussions with various pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, GSK and Sunovion, allowed for the acquisition of a regular supply of free demo-inhalers for each RT department to stock and utilize if they determine a specific patient could use further education regarding inhaler technique. These companies also provided RT-specific demo-inhaler technique education system-wide as deemed necessary by the local RT directors. Utilizing a nebulized medication delivery model can offer an option to significantly reduce respiratory medication costs in US hospitals based on our results, but in the opinion of the author it should be part of a larger more comprehensive program to improve patient care in our era of bundled payments and CMS penaltiesCitation35,Citation36. Case management and RT disease management programs in the COPD arena have been shown to significantly decrease LOS and readmissions, for exampleCitation41,Citation42.
After the implementation of this inhaler to nebulization protocol, there has been further work with standardizing COPD caresets in the EHR along with development of clinical practices with specific guideline and evidence-based recommendations on how to appropriately manage COPD patients system-wide, but these have only recently been implemented and should not have impacted any results mentioned here. At individual campuses throughout the healthcare system there may have been unknown local campus initiatives implemented that could have impacted these reported COPD LOS and 30 day readmission results, which is a limitation of this study. At the author’s facility, for example, there have been specific efforts in this regard, which may speak to possible impact.
Due to size and location, campus 1 () typically treats more COPD patients in the system annually vs. sister facilities. Prior to implementation of the inhaler to neb protocol in January 2016, our campus had the second worst COPD 30 day readmission rates in the system. Overall and CMS-specific readmissions rates were 21% and 20.8%, respectively in 2015. Previous to protocol implementation we had already initiated a COPD-specific RT-driven process to improve patient assessment and education by running a daily COPD patient-specific report available in the Cerner EHR. One of the components of this is to also utilize the In-Check Dial to determine PIFRs and document that information in the EHRCitation15,Citation43. The RT considers current inhalers the patient may have been on at home along with this information to determine appropriateness. Medication recommendations for discharge based on this PIFR assessment and other needs are placed in an EHR communication to both case management and physicians. After implementation of the inhaler to neb protocol which keeps patients on nebs until discharge, we furthered our efforts to bridge interdisciplinary involvement with case management and physicians. More education and information was provided to the case management department regarding inhaler and nebulization medication patient affordability resources that could facilitate discharge. These medication resources, such as arformoterol 2 week free supply vouchers and various inhaler free trial and/or co-pay cards are also kept in the on-campus retail pharmacy that fills discharge prescriptions. Additionally, we discovered issues with case management utilizing durable medical equipment (DME) providers to fill nebulizers and medications who were not well versed in the respiratory space, including Medicare Part B billing when nebulized medications may be more appropriate for low PIFR patients. Medicare Part B will better cover nebulizers and nebulized medications, but not inhalers, so this option may be a useful alternative to assist patients who have deficient insurance coverage and cannot afford inhalers under their Medicare Part D plans. Although these efforts still need continual refinement and re-emphasis with key stakeholders in the process, our COPD outcomes () appear to have improved more than the system average and continue to be significantly lower despite not utilizing inhalers for over 3 years.
It was, unfortunately, not possible to reliably determine objective information on the impact of this implementation on RT labor throughout the system secondary to complex variables and numerous non-static service lines provided by the RT departments. RT department staffing as it relates to pre-existing work burden ratios (units of service/RT full time equivalents [FTEs]) and bed burden ratios (beds/RT FTE) are also not consistent throughout the system. However, following a phased implementation approach allowed for numerous campuses serving different populations and staffing models to provide gradual feedback before subsequent facility inclusion. Follow-up with numerous RT directors has provided consistent feedback that they felt protocol management did not incur additional labor. It was communicated that adjustments in their staffing models enabled their ability to appropriately deal with any increases in neb deliveries in the first 4 hours of a shift, which moderated later in the day. As a result, if RTs do not typically administer inhalers to patients, before conversion it is important to consider whether RT shift times may differ from nursing and then re-assess when standard medication administration times (i.e. Q12H, Q8H, Q6H, Q4H, etc.) are given to be sure they coincide with appropriate RT work flow. EHR systems generally should have functionality that allows for clinical informatics to adjust standard respiratory medication administration times that a facility or health system will use. Another issue that should be evaluated is BCMA technology, which is often utilized to ensure administration of medications to the correct patient. In our health system, medication dispensing cabinets are stationed throughout hospitals. System medication management policy previously allowed for only 60 minutes before and after a scheduled standard medication time on the electronic medication administration record (eMAR) for staff to pull and scan meds without issue. This was changed to 90 minutes to increase BCMA flexibility and work flow. Facility RT practice habits as they relate to mixing of nebulized medications should be ascertained as well. During our assessment, we determined that many RT departments were not maximizing their ability to combine nebulized solutions based on available published literatureCitation44–48. As a result, available information was provided to all RT directors in the system to facilitate improvements at their campus. Depending on contract prices, Misty Fast or NebuTech nebulizers have also been brought in by some facilities for COPD patients specifically, which can deliver nebulizations over 4 minutes vs. 8 minutes with Misty Max or Aeroclipse II. This may also improve efficiency of staff depending on the complexities of EHR documentation and patient education tasks performed.
The cost-effectiveness of this delivery model may be US centric or in countries where the majority of inhalers are brand name-only and tend to be much more costly relative to nebulized medications. In 2019 there have been several FDA-approved generic or branded-generic versions of albuterol, fluticasone and fluticasone–salmeterol inhalers that have come to the US market; however, none of these come in institutional sizes and all are more expensive to our health system than the branded alternatives. The introduction of generic inhalers in the US is welcomed and will likely make inhalers more affordable to patients in the outpatient environment, but at this time they appear to offer little economically to US hospitals.
It is also important to state that this inhaler to nebulization protocol does not undermine a provider’s ability to treat AECOPD in the hospital setting with recommended medications per GOLD 2019. It is directing the delivery method to curb drug costs and waste. GOLD 2019 is specific in stating there is no significant difference in FEV1 when comparing MDI or nebulizer routes of medication deliveryCitation32. A SABA with or without a SAMA is the recommended initial first line bronchodilator treatment for the management of exacerbations. Systemic corticosteroids have been shown to shorten recovery time, improve lung function, improve oxygenation, and reduce relapse and treatment failure as well as shorten hospitalization time. Nebulized budesonide remains an available ICS; however, recent information suggests blood eosinophils may be a better predictor of effectivenessCitation32. There is also limited information that questions whether concomitant inhaled and systemic corticosteroid use in AECOPD confers appreciable benefitCitation49,Citation50. GOLD 2019 does suggest that maintenance therapy with long-acting bronchodilators be continued or initiated as soon as possible prior to hospital discharge, but this statement comes with the caveat and acknowledgement that there are no clinical studies that have evaluated the use of a LABA or LAMA with or without ICS during an exacerbationCitation32. The only medication that our protocol does not provide is a LAMA since a nebulized version did not exist on the US market at time of implementation. Yet on observation our overall readmission rates have decreased without use. As an observational study this does not imply that a subset of patients may not benefit in the institutionalized setting, but rather we did not note any negative ramifications of non-use and perhaps more importantly that randomized controlled trials supporting this GOLD recommendation are needed. Nevertheless, at this time nebulized LAMAs are now available in the US; however, they are poorly priced for acute care compared to the institutional sized inhaler options.
Loborec et al. converted all ipratropium/albuterol (Combivent) inhalers provided by a CC model to an equivalent nebulized regimen at their 1242-bed urban academic health system. They achieved significant extrapolated savings of $145,806 in the first year and $257,936 in subsequent years with just one inhaler, ipratropium–albuterol (Combivent), conversion after deducting one RT full-time equivalent (FTE) and initial capital expenditures. However, they acknowledge that the actual impact on RT labor was possibly overestimated by their prediction by 31.6%. Although they deducted labor costs off total savings, the RT department was unable to quantify the actual percentage of FTE time allocated to the formulary substitutionCitation24.
Strozyk et al. did a full conversion of all inhalers to a nebulization model at their 541-bed regional referral center to reduce therapeutic duplications, decrease inhaler waste and streamline the hospital formulary. RTs delivered all respiratory medications in both time frames and comparing seasonally adjusted 6 month periods they found that post-implementation the total number of respiratory treatments decreased by 9% (93,285 vs. 84,735), which was attributed to a reduction in therapeutic duplications. There was also no significant change in total RT workload statistics per patient day. RT productivity remained similar for the two periods at 116% and 110%. Patient satisfaction reportedly improved in the nebulization period. COPD LOS (5.3 days vs. 5.1 days) and COPD 30 day readmission rates (11% vs. 12%) remained stable. The number of formulary medications was reduced from 15 to 3, inhaler waste was eliminated, and medication costs decreased $196,533 (59%)Citation18. More recent reports of full inhaler conversions have also suggested similar successCitation6,Citation8,Citation17,Citation20–22.
Conclusion
To the author’s knowledge, despite inhaler to neb protocols being fairly common in many US hospitals, this is the first publication to attempt to illustrate the results for a large health system. Through a multi-disciplinary effort, the health system was able to develop and implement a comprehensive inhaler to nebulization protocol as a standardized model to deliver respiratory medications. This has significantly reduced delivery variations and drug costs without any observed negative impact on respiratory outcomes. If inhaler prices continue to follow historical inflation trends especially as new devices gain FDA approval, implementing a similar delivery model based on hospital-specific economic assessments may become more attractive to US health systems in an effort to deliver cost-effective care. Following a phased-implementation approach can allow for gradual internal feedback to ensure that a successful transition is achieved.
Transparency
Declaration of funding
This manuscript received no funding.
Author contributions: T.L. was responsible for all aspects of this paper as it relates to conceptualization as well as data gathering and analysis. The author received no assistance in drafting, revisions or final approval of the published version.
Declaration of financial/other relationships
T.L. has disclosed that he provides consulting services to Sunovion Pharmaceuticals in assisting US health systems interested in implementing inhaler to nebulization protocols. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgements
Deep gratitude is extended to Kim Ury and Nathan Spence for provision of much of the raw data necessary for this paper to be completed.
Related Research Data
References
- NORC at the University of Chicago. Final report: trends in hospital inpatient drug costs: issues and challenges [Internet]. 2016 [cited 2018 Dec 7]. Available from: https://www.aha.org/system/files/2018-01/aha-fah-rx-report.pdf
- GoodRx: here’s why asthma inhalers are so expensive [Internet]. [cited 2019 Jan 31]. Available from: https://www.goodrx.com/blog/heres-why-asthma-inhalers-are-so-expensive/
- Ford ES. Hospital discharges, readmissions, and ED visits for COPD or bronchiectasis among US adults: findings from the nationwide inpatient sample 2001–2012 and Nationwide Emergency Department Sample 2006–2011. Chest. 2015;147:989–998.
- Jinjuvadia C, Jinjuvadia R, Mandapakala C, et al. Trends in outcomes, financial burden, and mortality for acute exacerbation of chronic obstructive pulmonary disease (COPD) in the United States from 2002 to 2010. COPD. 2017;14:72–79. Feb
- Sakaan S, Ulrich D, Luo J, et al. Inhaler use in hospitalized patients with chronic obstructive pulmonary disease or asthma: assessment of wasted doses. Hosp Pharm. 2015;50:386–390.
- Ware MD, Nguyen T. Strategy to eliminate waste with metered dose inhalers (MDIs) in adult chronic obstructive pulmonary disease (COPD) patients in an acute care community hospital. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Larson T, Gudavalli R, Prater D, et al. Critical analysis of common canister programs: a review of cross-functional considerations and health system economics. Curr Med Res Opin. 2015;31:853–860.
- Glick J, Gonzalez E. Therapeutic interchange protocol of orally inhaled medications to administration via nebulizer: impact on the incidence and cost of wasted doses. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127:335–371.
- Press VG, Arora VM, Shah LM, et al. Misuse of respiratory inhalers in hospitalized patients with asthma or COPD. J Gen Intern Med. 2011;26:635–642.
- Tratto KD, Gomez C, Ryan CJ, et al. Nurses knowledge of inhaler technique in the inpatient hospital setting. Clin Nurse Spec. 2014;28:156–160.
- Sharma G, Mahler DA, Mayorga VM, et al. Prevalence of low peak inspiratory flow rates at discharge in patients hospitalized for COPD exacerbation. J COPD F. 2017;4:217–224.
- Loh CH, Peters SP, Lovings TM, et al. Suboptimal inspiratory flow rates are associated with chronic obstructive pulmonary disease and all-cause readmissions. Annals ATS. 2017;14:1305–1311.
- Ghosh S, Ohar JA, Drummond MB. Peak inspiratory flow rate in chronic obstructive pulmonary disease: implications for dry power inhalers. J Aersol Med Pulm Drug Deliv. 2017;30:381–387.
- Mahler DA. Peak inspiratory flow rate as a criterion for dry powder inhaler use in chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2017;14:1103–1107.
- Wild D. Bright ideas for boosting savings – and patient care [Internet]. Pharm Pract News; February 2014. [cited 2019 Jan 31]. Available from: https://www.pharmacypracticenews.com/Operations-and-Management/Article/02-14/Bright-Ideas-for-Boosting-Savings—and-Patient-Care/25850
- Yoon J, Hebert N, Freeland H. Efficacy of a protocol to eliminate use of metered-dose inhalers in favor of nebulization therapy for inpatient respiratory care. Chest. 2014;146:551A. (4_MeetingAbstracts): doi:10.1378/chest.1973537
- Strozyk W, Norris C, Ryman M. Quality, productivity and economic results of a metered dose inhaler to nebulizer interchange in a large, regional referral medical center. Poster presentation at the American Society of Health-System Pharmacists 2014 Midyear Clinical Meeting; Ahaheim, CA.
- McDonough K, Gonzalez S, Sunnongmuang S, et al. Therapeutic substitution of long acting beta agonist/corticosteroid metered dose inhalers arformoterol and budesonide via nebulization at a 210-bed urban hospital. Poster presentation at the American Society of Health-System Pharmacists 2012 Midyear Clinical Meeting; Las Vegas, NV.
- Glick J, Gonzalez E. Therapeutic interchange protocol of orally inhaled medications to administration via nebulizer: financial impact. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Glick J. Gonzalez E. Therapeutic interchange protocol or orally inhaled medications to administration via nebulizer: impact on the incidence of therapeutic duplications. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Glick J, Gonzalez E. Therapeutic interchange protocol or orally inhaled medications to administration via nebulizer: effect on workload of respiratory therapists and registered nurses. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Pitts C. Knoblock A. Evaluating a formulary substitution of inhaled fluticasone to nebulized budesonide. Poster presentation at the American Society of Health-System Pharmacists 2018 Midyear Clinical Meeting; Ahaheim, CA.
- Loborec SM, Johnson SE, Keating EA. Financial effect of converting ipratropium–albuterol therapy from inhalers to nebulizer treatments at an academic health system. Am J Health Syst Pharm. 2016;73:121–125.
- Streepy KS, Dawson AM, Grigonis AM, et al. Conversion from metered dose inhalers to a vibrating mesh nebulizer in long term acute care hospitals: cost effectiveness and respiratory staff perception. Poster presentation at the American Society of Health-System Pharmacists 2013; Orlando, FL.
- Blake G, Yaklic J, Cobb J. Transition from ipratropium/albuterol inhaler to nebulizer on quality and cost savings in ventilated patients. Poster presentation at the American Society of Health-System Pharmacists 2013 Midyear Clinical Meeting; Orlando, FL.
- McDaniel C, Glynn B, Gudowski S, et al. Conversion of pressurized metered-dose inhaler to vibrating mesh nebulizer administered medications. Poster session presented at: Society of Critical Care Medicine 42nd Critical Care Congress, 2013 Jan 19–23; San Juan, Puerto Rico. Poster 404.
- Emberger JS, Brown JM, Killian L. Cost reduction using Aeroneb Solo in a medical ICU ventilator population. Poster presented at: American Association of Respiratory Care Congress; 2011 Nov 7; Tampa, FL.
- Dubosky MN, Chen YF, Henriksen ME, et al. Vibrating mesh nebulizer compared with metered-dose inhaler in mechanically ventilated subjects. Respir Care. 2017;62:391–395.
- Myrdal PB, Sheth P, Stein SW. Advances in metered dose inhaler technology: formulation development. AAPS Pharm Sci Tech. 2014;15:434–455.
- Marcoux RM, Vogenberg FR. Hazardous waste compliance in health care settings. PT. 2015;40:115–118.
- From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) [Internet]. 2019. [cited 2019 Jan 31]. Available from: http://goldcopd.org.
- Quintana JM, Unzurrunzaga A, Garcia-Gutierrez S, et al. Predictors of hospital length of stay in patients with exacerbations of COPD: a cohort study. J Gen Intern Med. 2015;30:824–831.
- Shanley LA, Lin H, Flores G. Factors associated with length of stay for pediatric asthma hospitalizations. J Asthma. 2015;52:471–477.
- Sha T, Churpek MM, Perraillon MC, et al. Understanding why patients with COPD get readmitted. A large national study to delineate the Medicare population for the readmission penalty expansion. Chest. 2015;147:1219–1226.
- Rinne ST, Castaneda J, Lindenauer PK, et al. Chronic obstructive pulmonary disease readmissions and other measures of hospital quality. Am J Respir Crit Care Med. 2017;196:47–55.
- Ohar JA. Risks may not be reasons for COPD readmissions. Ann Am Thorac Soc. 2015;12:1259–1260.
- Alismail A, Song CA, Terry MH, et al. Diverse inhaler devices: a big challenge for health-care professionals. Respir Care. 2016;61:593–599.
- Plaza V, Giner J, Rodrigo GJ, et al. Errors in the use of inhalers by health care professionals: a systematic review. J Allergy Clin Immunol Pract. 2018;6:987–995.
- Braman SS, Carlin BW, Hanania NA, et al. Results of a pulmonologist survey regarding knowledge and practices with inhalation devices for COPD. Respir Care. 2018;63:840–848.
- Alshabanat A, Otterstatter MC, Sin DD, et al. Impact of a COPD comprehensive case management program on hospital length of stay and readmission rates. COPD. 2017;12:961–971.
- Silver PC, Kollef MH, Clinkscale D, et al. A respiratory therapist disease management program for subjects hospitalized with COPD. Respir Care. 2017;62:1–9.
- Sanders MJ. Guiding inspiratory flow: development of the In-Check dial G16, a tool for improving inhaler technique. Pulm Med. 2017;2017:1.
- Kamin W, Erdnuss F, Kramer I. Inhalation solutions – which ones may be mixed? Physico-chemical compatibility of drug solutions in nebulizers – update 2013. J Cyst Fibros. 2014;13:243–250.
- Burchett DK, Darko W, Zahra J, et al. Mixing and compatibility guide for commonly used aerosolized medications. Am J Health System Pharm. 2010;67:227–230.
- Bonasia P, Cook C, Cheng Y, et al. Compatibility of arformoterol tartrate inhalation solution with three nebulized drugs. Curr Med Res Opin. 2007;23:2477–2483.
- Bonasia PJ, McVicar WK, Bill W, et al. Chemical and physical compatibility of levalbuterol inhalation solution concentrate mixed with budesonide, ipratropium bromide, cromolyn sodium, or acetylcysteine sodium. Respir Care. 2008;53:1716–1722.
- Akapo S, Gupta J, Martinez E, et al. Compatibility and aerosol characteristics of formoterol fumarate mixed with other nebulizing solutions. Ann Pharmacother. 2008;42:1416–1424.
- Steuber T, Shiltz D. Single-center retrospective evaluation of inhaled corticosteroid use for chronic obstructive pulmonary disease exacerbation patients receiving systemic corticosteroids. Hosp Pharm. 2016;51:841–846.
- Pearce JA, Shiltz DL, Ding Q. Effectiveness and safety comparison for systemic corticosteroid therapy with and without inhaled corticosteroids for COPD exacerbation management. Ann Pharmacother. 2018;52:1070–1077.