Abstract
Objective:
Quantify the rates influenza vaccination and RSV prophylaxis for children with airway stenosis and/or other disorders and assess impact on resource utilization.
Methods:
This was a retrospective study with data extracted from Duke Enterprise Data Unified Content Explorer (DEDUCE) between January 1, 2006 and December 1, 2017. Children aged 18 years and younger with at least one diagnosis code for airway stenosis and/or disorders were included. The index date was defined as the first date of airway stenosis/disorders diagnosis. Each patient was followed for up to one year after the index date. Influenza vaccination or RSV prophylaxis documented within one year of index date were included. We defined emergency department (ED) visits and/or hospital admissions related to respiratory diagnoses as the primary outcome of increased resource utilization.
Results:
A total of 2718 patients were included. In our institution, our results have indicated that there are fairly low vaccination documentation rates of influenza vaccination, RSV prophylaxis, or both provided to children with airway stenosis/disorders, 14.1% (389/2718), 1.1% (30/2718), and 0.6% (17/2718), respectively, within the first year after diagnosis. Around 5% (139/2718) and 10% (269/2718) experienced ED visits or hospitalizations related to respiratory issues within the first year after diagnosis, respectively. Among 139 and 269 patients with ED visits or hospitalizations, 34 (25%) and 54 (20%) had multiple visits, respectively. Very few patients had documented influenza vaccination (11/139, 0.4%) or RSV prophylaxis (5/269, 0.18%) before ED visits or hospitalization.
Conclusions:
There is little available evidence at this time for strategies to prevent adverse events or complications in children with airway stenosis/disorders. In our institution, our results have indicated that there are fairly low documented rates of influenza vaccination, RSV prophylaxis, or both provided to children with airway stenosis/disorders in the first year after diagnosis. This is an area of significant clinical interest for potentially limiting adverse events and optimizing resource utilization for children with airway stenosis/disorders.
Keywords: influenza, subglottic stenosis, airway disorders, pediatric, RSV, palivizumab
Introduction
Airway disorders are a complex and challenging problem to manage in children and places a significant burden on health care resource utilization. For example, in 2003 alone, using a US national database registry for childrens’ hospitals, there were over two thousand admissions for subglottic stenosis and 10 deaths.1 And although it is a relatively rare disease, it is associated with high costs of treatment and management. The mean total charge of hospital admission for subglottic stenosis in 2003 was $53,787 with a mean total length of stay of 11.6 days. Predictors of high resource utilization for subglottic stenosis were patients who were emergently admission, under 1 year or age, longer hospital length of stay, increased number of procedures performed, among others.1 The clinical symptoms may range from a lack of any clinical symptomatology to dyspnea on exertion, activity limitations, respiratory distress, stridor, and/or tracheostomy dependency.
Limited data are available to quantify the resource utilization for areas of upper airway stenosis and disorders in the inpatient or outpatient setting. Pathology affecting this area may include acquired issues, such as subglottic stenosis from prolonged intubation or may also result from congenital problems such as tracheobronchomalacia. Clinical symptoms of airway disorders in children often are dictated by the severity the airway compromise, underlying comorbidities, such as neuromuscular and developmental delays, and the age of the patient. This is more clinically pronounced in children, especially newborns and infants, given the smaller diameter of their airways. Symptomatic patients may struggle with a number of respiratory issues, including tracheostomy dependence, recurrent hospitalizations, and/or feeding difficulties. Feeding difficulties and respiratory compromise may result in failure to thrive in newborns in infants, resulting in significant developmental delay and a lifetime of chronic medical issues.
Given these children’s underlying chronic airway issues, they may be susceptible to complications related to acute viral infections, which may precipitate acute on chronic respiratory failure. A number of viral infections may predispose children to acute respiratory failure resulting in endotracheal intubation or mechanical ventilation and subsequent further exacerbation of airway pathology. Respiratory syncytial virus (RSV) and influenza are two common pathogens that may result in acute respiratory failure. Children with airway stenosis or disorders may be at risk for significant clinical complications related to contracting one or both of these viral pathogens. Consequently, our study objective was to investigate the prevalence of vaccination for influenza and RSV prophylaxis within one year of diagnosis of an airway disorder in a cohort of children cared for at our academic, tertiary-care children’s hospital and assess resource utilization trends for these children.
Methods
This retrospective study utilized data extracted from Duke Enterprise Data Unified Content Explorer (DEDUCE) between January 1, 2006 and December 1, 2017. Children aged 18 years and younger with at least one of the diagnosis codes for airway stenosis and/or disorders (ICD-9-CM diagnosis codes 460 – 519; ICD-10-CM: J38.1, J38.6, J39.8, J98.09, Q31.1, Q31.3, Q31.8, Q32.1, and Q32.4) were included. An index date was created and defined as the first date of airway stenosis/disorders diagnosis. We defined the upper respiratory viral season from September to the following March, and looked at that time period for children who received influenza or/and RSV prophylaxis. The effect of the vaccination was presumed to last for one year until the next viral season. We only considered vaccination after and within one year of the index date. Influenza vaccination or RSV prophylaxis documented within one year of index date were assessed, along with post-vaccination or RSV prophylaxis ED visits or hospitalizations related to respiratory diagnoses. Diagnosis and CPT codes were used to identify patients who received influenza vaccination. (Appendix 1) Propensity matched non-vaccinated patients were compared with vaccinated patients within the same year. Suppose a patient was vaccinated at month 3 after index date, this vaccinated patient was matched with one or multiple non-vaccinated patients who did not have ED visits and hospitalization before month 3. This allowed the two groups to be comparable and have equal length of follow-up.
Patient characteristics, such as gender, age, race/ethnicity, year of diagnosis, and comorbidities (endocrine, nutritional, and metabolic disease; disease of the blood and blood-forming organs; diseases of the nervous system and sense organs; diseases of the digestive system, disease of genitourinary system, diseases of the musculoskeletal system and connective tissue; congenital anomalies; cardiopulmonary disease; asthma; obesity; and weight loss) were collected from electronic health records on the same date of index date. Duke University Medical Center Institutional Review Board (IRB) approval was obtained prior to our investigation.
The primary outcome of increased resource utilization was defined as emergency department (ED) visits and/or hospital admissions related to respiratory diagnoses (ICD-9-CM: 460 – 519; ICD-10-CM: J00-J99) within one year of the index date. The numbers of patients with airway stenosis/disorders for each year were plotted. The frequency and calendar month of influenza vaccination and RSV prophylaxis were tabulated. We then assessed those children during the calendar time period in which they would be at risk for influenza infection and may have been vaccinated, which was from September to the following March. All analyses were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC).
Results
A total of 2718 children were identified with airway stenosis/disorders. (Figure 1) The demographic characteristics of the cohort are reported in Table 1. The mean age at first SGS diagnosis was 2.1 years old (SD 4.2) and the median age was 0 years old, indicating that most patients had the diagnosis of airway stenosis/disorders when they were infants. A majority of the patients (58.4%) were male. Our cohort had a high proportion of patients with digestive system disease (40.7%) and congenital anomalies (83.3%). Figure 2 depicts the trend of airway stenosis/disorders diagnosis over the calendar year.
Fig. 1.
Children identified with diagnosis of airway stenosis or disorder.
Table 1.
Patient demographic information by vaccination groups
| No documentation of influenza or RSV vaccine (N=2282) | Had both influenza and RSV vaccine documented (N=17) | Only documentation of influenza vaccine (N=389) | Only documentation of RSV vaccine (N=30) | Total (N=2718) | |
|---|---|---|---|---|---|
| Patient gender | |||||
| Female | 957 (41.9%) | 6 (35.3%) | 158 (40.6%) | 11 (36.7%) | 1132 (41.6%) |
| Male | 1325 (58.1%) | 11 (64.7%) | 231 (59.4%) | 19 (63.3%) | 1586 (58.4%) |
| Age at first SGS diagnosis (years) | |||||
| Mean (SD) | 2.3 (4.4) | 0.0 (0.0) | 0.8 (2.4) | 0.2 (0.6) | 2.1 (4.2) |
| Median (Q1, Q3) | 0 (0.0, 2.0) | 0 (0.0, 0.0) | 0 (0.0, 0.0) | 0 (0.0, 0.0) | 0 (0.0, 2.0) |
| Patient Race | |||||
| Black/African American | 748 (32.8%) | 11 (64.7%) | 170 (43.7%) | 12 (40.0%) | 941 (34.6%) |
| Caucasian/White | 1165 (51.1%) | 3 (17.6%) | 137 (35.2%) | 11 (36.7%) | 1316 (48.4%) |
| Other or Unknown | 369 (16.2%) | 3 (17.6%) | 82 (21.1%) | 7 (23.3%) | 461 (17.0%) |
| Endocrine/Nutritional/Metabolic/Immunity Disease | 528 (23.1%) | 14 (82.4%) | 62 (15.9%) | 23 (76.7%) | 627 (23.1%) |
| Blood and Blood-Forming Organs Diseases | 269 (11.8%) | 10 (58.8%) | 32 (8.2%) | 18 (60.0%) | 329 (12.1%) |
| Nervous System and Sense Organs Diseases | 540 (23.7%) | 14 (82.4%) | 77 (19.8%) | 18 (60.0%) | 649 (23.9%) |
| Digestive System Diseases | 935 (41.0%) | 16 (94.1%) | 131 (33.7%) | 25 (83.3%) | 1107 (40.7%) |
| Genitourinary System Diseases | 271 (11.9%) | 9 (52.9%) | 32 (8.2%) | 18 (60.0%) | 330 (12.1%) |
| Musculoskeletal/Connective Tissue Diseases | 135 (5.9%) | 4 (23.5%) | 21 (5.4%) | 6 (20.0%) | 166 (6.1%) |
| Congenital Anomalies | 1898 (83.2%) | 16 (94.1%) | 321 (82.5%) | 28 (93.3%) | 2263 (83.3%) |
| Congestive heart failure | 130 (5.7%) | 2 (11.8%) | 6 (1.5%) | 7 (23.3%) | 145 (5.3%) |
| Valvular Disease | 100 (4.4%) | 5 (29.4%) | 14 (3.6%) | 7 (23.3%) | 126 (4.6%) |
| Pulmonary circulation disorder | 67 (2.9%) | 2 (11.8%) | 8 (2.1%) | 4 (13.3%) | 81 (3.0%) |
| Cardiopulmonary disease | 226 (9.9%) | 7 (41.2%) | 22 (5.7%) | 13 (43.3%) | 268 (9.9%) |
| Asthma | 358 (15.7%) | 0 (0.0%) | 26 (6.7%) | 3 (10.0%) | 387 (14.2%) |
| Obesity | 10 (0.4%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 10 (0.4%) |
| Weight Loss | 40 (1.8%) | 0 (0.0%) | 1 (0.3%) | 1 (3.3%) | 42 (1.5%) |
Fig. 2.
Calendar distribution of airway stenosis or disorder diagnosis
A majority of the identified patients, 2282 (86.96%) did not have documentations of either influenza vaccination or RSV prophylaxis within one year of diagnosis of airway stenosis. 390 (14.4%) of those children had an ED visit or hospitalization within first year after index date. 389 (14.3%) patients had only documented influenza vaccination but not RSV prophylaxis within the first year after diagnosis of airway stenosis. 30 (1.1%) children only had RSV prophylaxis documentation but not influenza vaccination within the first year after diagnosis of airway stenosis. Lastly, only 17 (0.6%) children with airway stenosis/disorders had both influenza vaccination and RSV prophylaxis documentations within the first year after diagnosis. We found a seasonal trend of influenza vaccination demonstrating that most, 87% (536/616), were between September and January (Figure 2b). Similarly, most RSV prophylaxis (96.7%, 58/60) were provided from October to March (Figure 2c).
The majority of patients with both documented influenza vaccination and RSV prophylaxis were African American, 64.7% (11/17), whereas only 32.8% (748/2282) of patients without documented vaccination were African American (Table 1). Compared to patients without documented vaccination, patients with documented RSV prophylaxis with or without influenza vaccination were sicker in terms of comorbidities on the index date. These included a higher proportion of patients with endocrine/nutritional/metabolic/immunity disease (82.4% and 76.7% vs. 23.1%), blood and blood-forming organs diseases (58.8% and 60% vs. 11.8%), nervous system and sense organs diseases (82.4% and 60% vs. 23.7%), digestive system diseases (94.1% and 83.3% vs. 41%), genitourinary system diseases (52.9% and 60% vs. 11.9%), musculoskeletal/connective tissue diseases (23.5% and 20% vs. 5.9%), congenital anomalies (94.1% and 93.3% vs. 83.2%), congestive heart failure (11.8% and 23.3% vs. 5.7%), valvular disease (29.4% and 23.3% vs. 4.4%), pulmonary circulation disorder (11.8% and 13.3% vs. 2.9%), and cardiopulmonary disease (41.2% and 43.3% vs. 9.9%).
Most patients, 2579 (95%), did not have any ED visits within one year after index date. For 139 patients who had ED visits within one year, most patients, 105 (75.54%), had a single ED visit and 34 (24.46%) had multiple ED visits. Most patients, 2449 (90.10%), were not hospitalized within one year after the index date. For 269 patients who were hospitalized within one year, 215 (79.93%) had a single hospitalization and 54 (20.07%) had multiple hospitalizations.
Among 389 patients with documented influenza vaccination but not RSV prophylaxis within one-year of index date, 8 (2.1%) of them were noted to have an ED visit and/or hospitalization related to a primary respiratory diagnosis after vaccination. Eight out of 30 (26.7%) children with documented RSV prophylaxis but not influenza vaccination were noted to have an ER visit and/or hospitalization related to a primary respiratory diagnosis after vaccination. None of the 17 children with both documented influenza and RSV prophylaxis were hospitalized or had an ED visit in the year following.
Discussion
Our current understanding of optimal care of children with airway stenosis/disorders is far from complete. There are no guidelines or best practice models available to help guide clinicians manage children with airway stenosis/disorders. When approaching surgical care for children with airway disorders, the focus has been on improving clinical outcomes through developing innovative surgical and procedural options for managing these patients. It is possible that we are missing an opportunity to highlight and investigate other adjunctive options that may have a positive impact on the overall health of this medically fragile patient population. One such opportunity lies in the question: what is the role of influenza vaccination and/or RSV prophylaxis for these children? These children are clearly at increased risks for respiratory complications related to infection. With upper respiratory viral infections, such as RSV and influenza, they may cause acute exacerbations in the airway of children with airway disorders who are already at risk for respiratory failure. Currently, a recombinant, monoclonal antibody, palivizumab, is available for infants and children at high risk for complications related to this infection. Guidelines for those who would benefit can be found in Table 2.2 Notably absent is any recommendation for children with airway stenosis and/or other airway disorders. Current evidence is insufficient to support more expanded indications for cost-effectiveness; however, sub-groups of children with multiple risk factors apart from gestational age and birth age may benefit from RSV prophylaxis. The authors recommend that future study investigate larger, better powered and reported studies to derive more accurate estimates of the risk factor effect sizes of which include children with airway stenosis and/or other airway disorders.3
Table 2.
Selected recommendations from the 2014 American Academy of Pediatrics (AAP) RSV immunoprophylaxis guide for children at increased risk of hospitalization for RSV infection.
| Population | 2014 AAP Policy |
|---|---|
| ≤28 weeks gestational age | Recommended |
| 29 – 31 weeks gestational age | Not recommended unless other qualifying conditions |
| 32 – 34 weeks gestational age | Not recommended unless other qualifying conditions |
| 35 weeks gestational age | Not recommended unless other qualifying conditions |
| Chronic lung disease | • ≤12 mo chronological age since birth at RSV season start • 12 – 24 mo chronological age since birth and requiring medical therapy within 6 mo of RSV season start |
| Congenital heart disease | ≦12 mo CA at RSV season start with noncyanotic heart disease |
Annual influenza vaccination is recommended to all children, but this may be especially prudent in children with airway stenosis/disorders to try to prevent and avoid associated respiratory complications. Inactivated quadrivalent influenza vaccine (QIV) has been demonstrated to be effective in preventing influenza in children.4 A systematic review of influenza vaccination programs has also demonstrated cost-effectiveness in children, and the authors recommend targeting and evaluating high risk populations.5 Furthermore, compared to other childhood vaccinations, influenza vaccination may offer an even more cost effective strategy when compared with human papilloma virus (HPV) varicella, rotavirus, hepatitis B, meningococcal disease, pneumococcal disease.6 Our current investigation appears to suggest that from documentation, influenza vaccination is far from complete.
Little evidence and research has been presented on ways to prevent complications in children with airway stenosis/disorders. Specifically, there are no prior investigations looking at the potential benefit that palivizumab or influenza vaccination may have on resource utilization, as a preventative measure to limit resource utilization and improve measures of quality of care, such as hospitalizations, increased operative interventions, costs, and/or mortality. It is unclear at this time if palivizumab may be of benefit for children with airway disorders, although one group has suggested that there may be some potential benefit in optimizing perioperative surgical outcomes for pediatric airway reconstruction.7 There is no available evidence at this time for the potential impact of influenza vaccination on resource utilization for children with airway disorders.
Unfortunately, we were unable to provide any conclusive evidence to answer this clinical question. However, our investigation does raise some very interesting insights and clinical questions that may benefit from further inquiry. First, in our institution, our results have indicated that there are fairly low rates of influenza vaccination, RSV prophylaxis, or both influenza vaccination and RSV prophylaxis documented for children with airway stenosis/disorders, 14.1%, 1.1%, and 0.6%, respectively, within the first year after diagnosis. Of clinical significance, we have also demonstrated that a number of children, around 5% and 10%, with airway stenosis/disorders experience ED visits or hospitalizations, respectively, related to respiratory issues within the first year after diagnosis. Of those that did have ED visits, it is of concern that approximately one-fourth of them had multiple visits; and one-fifth of them had multiple hospitalizations within the first year after diagnosis. These may be future areas to focus and investigate quality improvement and resource optimization strategies. It would be interesting to investigate if increased rates of influenza vaccination or RSV prophylaxis were able to affect resource utilization and/or improve quality of care. As there is a distinct and important temporal relationship between influenza vaccination or RSV prophylaxis administration, this may be best suited for database investigation and/or prospective study.
Our investigation has several and significant limitations inherent to a retrospective review, including accuracy and completeness of coding and charting. Problems such as, failure to document vaccination or the child received at an outside facility, may have played a role in our results. A significant challenge in this investigation was the insufficient number of children with airway disorders who received either influenza vaccination and/or RSV prophylaxis prior to first ED visit and/or hospitalization within the first year after the index date to perform. As a result, a logistic regression was not able to be performed, and we were not able to draw any specific conclusions. Another significant limitation included the potential for loss of follow up after diagnosis of airway stenosis/disorder and discharge from the hospital. Our institution is a regional referral hospital, and it is possible that children were lost to follow up because of distance and location. We also did not look at potential medical or insurance factors that may have prohibited or medically contraindicated children with airway stenosis/disorders from receiving influenza vaccination and/or RSV prophylaxis.
Conclusions
There is little available evidence at this time for non-surgical, adjunctive strategies to limit adverse events or complications in children with airway stenosis/disorders. One particular area that has not been investigated is the potential impact of influenza vaccination and/or RSV prophylaxis on resource utilization or optimizing preventative strategies for children with airway stenosis/disorders. We were unable to provide any conclusive evidence with our current investigation. In our institution, our results have indicated that there are fairly low documented rates of influenza vaccination, RSV prophylaxis, or both provided to children with airway stenosis/disorders in the first year after diagnosis. A significant number of these children experience multiple ED visits and hospitalizations. This is an area of significant clinical interest for potentially limiting adverse events and optimizing resource utilization for children with airway stenosis/disorders.
Acknowledgments
Funding sources: Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002553. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Appendix 1
Influenza vaccination:
ICD-9-CM: 99.52, v04.81
ICD-10-CM: Z23
CPT: 90653, 90654, 90655, 90656, 90657, 90658, 90659, 90660, 90661, 90662, 90672, 90673, 90674, 90682, 90685, 90686, 90687, 90688, 90724, and 90756
RSV prophylaxis:
ICD9: V04.82
ICD10: Z29.11
CPT: 90378 and 90379
Footnotes
Conflicts of interest: none.
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