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1578 Background: Acute care visits (emergency department [ED] visits or inpatient admissions) for patients with cancer are growing disproportionately. Traditional oncology care models have not effectively identified and managed at-risk patients to prevent acute care. A next step is to harness advances in technology and mobile applications to enable patients to report symptoms any time, enabling “digital hovering” - intensive monitoring and management of high-risk patients. Our objective was to evaluate a digital platform that identifies and remotely monitors high-risk patients initiating intravenous antineoplastic therapy with the goal of preventing unnecessary acute care visits. Methods: This was a single-institution matched cohort quality improvement study conducted at an NCI-designated cancer center between January 1, 2019 and March 31, 2020. Eligible patients were those initiating intravenous antineoplastic therapy who were identified as high-risk for seeking acute care. Patients were identified as high-risk for an acute care visit by their oncologist with decision support from a web-based machine learning model. Enrolled patients’ symptoms were monitored using a digital platform. The platform is integrated into the EMR and includes: 1) a secure patient portal enabling communication and daily delivery of electronic patient-reported outcomes symptom assessments; 2) clinical alerts for concerning symptoms; and 3) a symptom trending application. A dedicated team of registered nurses and nurse practitioners managed reported symptoms. These clinicians acted as an extension of the primary oncology team, assisting with patient management exclusively through the platform. The primary outcomes evaluated were incidence of ED visits and inpatient admissions within six months of intravenous antineoplastic initiation. Results: Eighty-one high-risk patients from the intervention arm were matched by stage and disease with contemporaneous high-risk control patients. Matched cohorts had similar baseline characteristics, including age, sex, race, and treatment. ED visits and hospitalizations within six months of treatment initiation were analyzed using cumulative incidence analyses with a competing risk of death. The cumulative incidence of an ED visit for the intervention cohort was 0.27 (95% CI: 0.17, 0.37) at six months compared to 0.47 (95% CI: 0.36, 0.58) in the control group (p = 0.01). The cumulative incidence of an inpatient admission was 0.23 (95% CI: 0.14, 0.33) in the intervention group versus 0.41 (95% CI: 0.30, 0.51) in the control group (p = 0.02). Conclusions: The narrow employment of technology solutions to complex care delivery challenges in oncology can improve outcomes and innovate care. This program was a first step in using a digital platform and a remote team to improve symptom care in the home for high-risk patients.

Ambulatory surgery centers (ASC) serve an important role for hospital systems of increasing operating capacity and offloading patient volume. When seeking to perform more complex cancer surgeries at an ASC, a systematic approach with care pathways can yield success by facilitating quick recovery for patients and reducing complication rates. End-to-end patient engagement is a key component of patient-centered care at the Josie Robertson Surgery Center and begins the moment the decision to have surgery is made and extends to the postdischarge period to track recovery. Engagement includes comprehensive education, standardization of processes, and setting clear expectations for recovery and discharge.

PURPOSE: Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well-characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. METHODS: In 2016, electronic patient-reported symptom monitoring began at our institution’s ambulatory surgery center. We retrospectively reviewed patients treated with minimally-invasive RP, who were sent a daily questionnaire completed using a web-interface until postoperative day 10. Severe symptoms automatically generate a “yellow alert,” which messages the clinic, while very severe symptoms generate a “red alert,” additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30- or 90-d complications (≥grade 2) based on the presence of alert symptoms. RESULTS: Of 2266 men undergoing RP, 1942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea, and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-d complications, but rates were low and differences between groups were non-significant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3%−3.5%; p = 0.3). Results were similar examining 90-d complications. CONCLUSIONS: While symptoms are common after RP, substantial improvements occur over the first 10 d. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.

Objective To evaluate the feasibility of an electronic symptom-tracking platform for patients recovering from ambulatory surgery. Method We assessed user response to an electronic system designed to self-report symptoms. Endpoints included compliance, postoperative symptoms, patient satisfaction. An 8-item symptom inventory (pain, nausea, vomiting, shortness of breath, fever, swelling, discharge, redness) was developed and made available on postoperative days (POD) 2–6. Responses exceeding defined thresholds of severity triggered alerts to healthcare providers. Symptoms, alerts, actions taken, urgent care center (UCC) visits, hospital admissions were tracked until POD 30. Patient satisfaction was evaluated on POD 7. A patient was defined as “responder” if at least 5/8 items on at least 3 PODs were completed. The assessment method was deemed successful if 64/100 patients responded. Results 97/102 patients were evaluable; 65 met “responder” criteria (67% responder rate; 95% CI 57–76%). 321 surveys were completed (median 4/patient), 248 (77%) in ≤2 min. Involving caregivers and allowing additional symptom-reporting improved the responder rate to 72% (95% CI 58–84%). Most commonly-reported moderate, severe, very severe symptoms were pain, nausea, swelling; 71% reported moderate to very severe pain on POD 2. Phone calls and adjustment of medications adequately addressed most symptoms. Two patients (2%) presented at UCC before, 6 (6%) after, POD 6; 1 (1%) was admitted. Most agreed or strongly agreed that electronic symptom-tracking was helpful, easy to use, and would recommend it to others. Conclusion Electronic symptom-tracking is feasible for patients undergoing ambulatory gynecologic cancer surgery. Symptom burden is high in the early postoperative period. Addressing patient-reported symptoms in a timely, automated manner may prevent severe downstream adverse events, reduce UCC visits and admission rates, and improve outcomes., Highlights • This study assessed user response of an electronic system designed to self-report symptoms. • Electronic postoperative symptom-tracking is feasible for patients undergoing ambulatory gynecologic cancer surgery. • Symptom burden is high in the early postoperative period. • Electronic patient-reported symptom-tracking reduces adverse events and urgent care/readmission rates and improves outcomes.

BACKGROUND: Whether routinely prescribed opioids are necessary for pain control after discharge among lumpectomy/sentinel node biopsy (Lump/SLNB) patients is unclear. We hypothesized that Lump/SLNB patients could be discharged without opioids with a failure rate of

Minimally invasive operative techniques and enhanced recovery after surgery (ERAS) protocols have transformed clinical practice and made it possible to perform increasingly complex oncologic procedures in the ambulatory setting, with recovery at home after a single overnight stay. Capitalizing on these changes, Memorial Sloan Kettering Cancer Center's Josie Robertson Surgery Center (JRSC), a freestanding ambulatory surgery facility, was established to provide both outpatient procedures and several surgeries that had previously been performed in the inpatient setting, newly transitioned to this ambulatory extended recovery (AXR) model. However, the JRSC core mission goes beyond rapid recovery, aiming to be an innovation center with a focus on superlative patient experience and engagement, efficiency, and data-driven continuous improvement. Here, we describe the JRSC genesis, design, care model, and outcome tracking and quality improvement efforts to provide an example of successful, patient-centered surgical care for select patients undergoing relatively complex procedures in an ambulatory setting.

Background and objectives Remifentanil infusion is used as an intraoperative anesthetic for thyroidectomy, but has been associated with acute opioid tolerance and hyperalgesia. A national shortage of remifentanil provided an opportunity to study postoperative pain in patients undergoing thyroidectomy. Methods Retrospective review of prospectively collected data from an outpatient surgery center. Primary analysis compared patients treated before and after remifentanil shortage. Results Median postoperative opioid consumption was 20 morphine milligram equivalents (MMEs) among those treated in the high-dose period and 15 MMEs in the low-dose period. Remifentanil/weight received was a significant predictor of requiring a postoperative narcotic (P = .006). Total non-remifentanil narcotics administered were equivalent but patients in the low dose period received higher amounts of intraoperative long-acting narcotics. Conclusions Remifentanil infusion for thyroid surgery is associated with higher postoperative pain and postoperative narcotics requirement. While a hyperalgesia state is possible, shifting of longer-acting narcotics from intraoperative to postoperatively is also supported.

BACKGROUND: In the short-stay surgery setting, where patients remain in hospital for a single overnight at most, it is unclear as to whether postoperative length of stay is a good surrogate for assessing rapidity of recovery. We hypothesized that length of stay would be a function of time of surgery and would be a poorer marker of recovery than time of discharge. METHODS: A cohort of 891 mastectomy and 538 prostatectomy patients had a planned single overnight stay after surgery at an ambulatory surgical hospital during 2016. The relationship between surgical start time and postoperative length of stay or discharge time was assessed. RESULTS: For both mastectomy and prostatectomy patients, 75% of patients were discharged between 10 AM and 12 noon and the median postoperative length of stay was 20 hours. There was a strong association between time of surgery and calculated length of stay. For mastectomies, having a surgery which begins at 6 PM vs 8 AM results in an estimated decrease of 8.8 hours (95% CI, 8.3–9.3) in postoperative length of stay but only 1.2 hours (95% CI, 0.77–1.6) later time of discharge. For prostatectomies, the estimated difference is a decrease of 6.9 hours (95% CI, 6.4–7.4) for postoperative length of stay and 2.5 hours (95% CI, 2.0–3.0) later discharge time. CONCLUSIONS: Postoperative length of stay is a poor outcome measure in a short-stay setting. When assessing rapidity of recovery for single overnight stay patients, we advocate the use of discharge time with adjustment for surgery start time. The effect of surgery start time on both postoperative length of stay and discharge time should be investigated to ascertain which is best to assess rapidity of recovery in other ambulatory care settings where recovery involves a single overnight stay. (Anesth Analg 2019;129:1007–13)

Electronic patient-reported outcomes (ePROs) may have the potential to improve cancer care delivery by enhancing patient quality of life, reducing acute care visits, and extending overall survival. However, the optimal cadence of ePRO assessments is unknown.To determine patient response preferences and the clinical value associated with a daily cadence for ePROs for patients receiving antineoplastic treatment.This quality improvement study of adult patients undergoing antineoplastic treatment assessed a remote monitoring program using ePROs that was developed to manage cancer therapy-related symptoms. ePRO data submitted between October 16, 2018 to February 29, 2020, from a single regional site within the Memorial Sloan Kettering Cancer Center network were included. Data were analyzed from April 2020 to January 2022.While undergoing active treatment, patients received a daily ePRO assessment that, based on patient responses, generated yellow (moderate) or red (severe) symptom alerts that were sent to clinicians.The main outcomes assessed included patient response rate, symptom alert frequency, and an analysis of the clinical value of daily ePROs.A total of 217 patients (median [range] age, 66 [31-92] years; 103 [47.5%] women and 114 [52.5%] men) initiating antineoplastic therapy at high risk for symptoms were monitored for a median (range) of 91 (2-369) days. Most patients had thoracic (59 patients [27.2%]), head and neck (48 patients [22.1%]), or gastrointestinal (43 patients [19.8%]) malignant neoplasms. Of 14 603 unique symptom assessments completed, 7349 (50.3%) generated red or yellow symptom alerts. Symptoms commonly generating alerts included pain (665 assessments [23.0%]) and functional status (465 assessments [16.1%]). Most assessments (8438 assessments [57.8%]) were completed at home during regular clinic hours (ie, 9 am-5 pm), with higher response rates on weekdays (58.4%; 95% CI, 57.5%-59.5%) than on weekend days (51.3%; 95% CI, 49.5%-53.1%). Importantly, 284 of 630 unique red alerts (45.1%) surfaced without a prior yellow alert for the same symptom within the prior 7 days; symptom severity fluctuated over the course of a week, and symptom assessments generating a red alert were followed by an acute care visit within 7 days 8.7% of the time compared with 2.9% for assessments without a red alert.These findings suggest that daily ePRO assessments were associated with increased insight into symptom management in patients undergoing antineoplastic treatment and symptom alerts were associated with risk of acute care.

PURPOSE: Early detection and management of symptoms in patients with cancer improves outcomes. However, the optimal approach to symptom monitoring and management is unknown. InSight Care is a mobile health intervention that captures symptom data and facilitates patient-provider communication to mitigate symptom escalation. PATIENTS AND METHODS: Patients initiating antineoplastic treatment at a Memorial Sloan Kettering regional location were eligible. Technology supporting the program included the following: a predictive model that identified patient risk for a potentially preventable acute care visit; a secure patient portal enabling communication, televisits, and daily delivery of patient symptom assessments; alerts for concerning symptoms; and a symptom-trending application. The main outcomes of the pilot were feasibility and acceptability evaluated through enrollment and response rates and symptom alerts, and perceived value evaluated on the basis of qualitative patient and provider interviews. RESULTS: The pilot program enrolled 100 high-risk patients with solid tumors and lymphoma (29% of new treatment starts v goal of 25%). Over 6 months of follow-up, the daily symptom assessment response rate was 56% (the goal was 50%), and 93% of patients generated a severe symptom alert. Patients and providers perceived value in the program, and archetypes were developed for program improvement. Enrolled patients were less likely to use acute care than were other high-risk patients. CONCLUSION: InSight Care was feasible and holds the potential to improve patient care and decrease facility-based care. Future work should focus on optimizing the cadence of patient assessments, the workforce supporting remote symptom management, and the return of symptom data to patients and clinical teams.

Background Overprescribing of opioids after surgery contributes to long-term abuse. Evaluating opioid prescription patterns and patient-reported opioid use offers an evidence-based method to identify potential overprescription. This quality improvement initiative aimed to reduce and standardize opioid prescriptions upon discharge from an ambulatory oncologic surgery center and evaluate the effect of this change on patients’ subsequent opioid use and reported pain. Methods Between March 2018 and January 2019, consecutive opioid-naive patients aged ≥ 18 years who underwent robotic or laparoscopic hysterectomy, radical prostatectomy, or partial nephrectomy, or total mastectomy with or without immediate reconstruction were surveyed 7–10 days postoperatively. Data collected in the pre- (n = 551) and post-standardization (n = 480) cohorts included perception of pain relief, opioids prescribed (verified by electronic medical record review) and consumed, and refills received. Results Pre-standardization, the median opioid prescription at discharge was 20 pills (interquartile range [IQR] 20–28) or 140 oral morphine milligram equivalents (MME) (IQR 100–150). Median opioid consumption was 2 pills (IQR 0–7) or 10 MME (IQR 0–40) among all services. Opioid prescriptions were later standardized to 7, 8, and 10 pills (35, 40, and 75 MME), in the gynecology, urology, and breast services, respectively. The change was not associated with an increase in reported pain. Refill requests increased postintervention across all surgeries from 4.4% to 7.7%, with the largest increase among patients who underwent breast surgery. Conclusion The number of opioid pills given at discharge to patients undergoing ambulatory or short-stay cancer surgery can safely be reduced.

PURPOSE To create a risk prediction model that identifies patients at high risk for a potentially preventable acute care visit (PPACV). PATIENTS AND METHODS We developed a risk model that used electronic medical record data from initial visit to first antineoplastic administration for new patients at Memorial Sloan Kettering Cancer Center from January 2014 to September 2018. The final time-weighted least absolute shrinkage and selection operator model was chosen on the basis of clinical and statistical significance. The model was refined to predict risk on the basis of 270 clinically relevant data features spanning sociodemographics, malignancy and treatment characteristics, laboratory results, medical and social history, medications, and prior acute care encounters. The binary dependent variable was occurrence of a PPACV within the first 6 months of treatment. There were 8,067 observations for new-start antineoplastic therapy in our training set, 1,211 in the validation set, and 1,294 in the testing set. RESULTS A total of 3,727 patients experienced a PPACV within 6 months of treatment start. Specific features that determined risk were surfaced in a web application, riskExplorer, to enable clinician review of patient-specific risk. The positive predictive value of a PPACV among patients in the top quartile of model risk was 42%. This quartile accounted for 35% of patients with PPACVs and 51% of potentially preventable inpatient bed days. The model C-statistic was 0.65. CONCLUSION Our clinically relevant model identified the patients responsible for 35% of PPACVs and more than half of the inpatient beds used by the cohort. Additional research is needed to determine whether targeting these high-risk patients with symptom management interventions could improve care delivery by reducing PPACVs.

Purpose The purpose of this paper is to determine the impact of having a patient-designated caregiver remain overnight with ambulatory extended recovery patients on early postoperative clinical outcomes. Design/methodology/approach This was a retrospective cohort study of patients undergoing surgery requiring overnight stay in a highly resourced free-standing oncology ambulatory surgery center. Postoperative outcomes in patients who had caregivers stay with them overnight were compared with outcomes in those who did not. All other care was standardized. Primary outcomes were postoperative length of stay, hospital readmission rates, urgent care center (UCC) visits within 30 days and perioperative complication rates. Findings Among patients staying overnight, 2,462 (57 percent) were accompanied by overnight caregivers. In this group, time to discharge was significantly lower. Readmissions (though rare) were slightly higher, though the difference was not statistically significant (p=0.059). No difference in early ( Originality/value This study is unique in its evaluation of the clinical impact of having a caregiver stay overnight with ambulatory surgery patients. Little research has focused on the direct impact of the caregiver on patient outcomes, especially in the ambulatory setting. With increased adoption of minimally invasive surgical techniques and enhanced recovery pathways, a larger number of patients are eligible for short-stay ambulatory surgery. Factors that impact discharge and early postoperative complications are important.

Although a deficiency of surfactant protein B (SFTPB) has been associated with lung injury, SFTPB expression has not yet been linked with nicotinamide phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB expression and lung inflammation were investigated in a LPS-induced ALI mouse model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression, achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing epithelial-specific transgene Cre or by the use of epithelial-specific expression of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI. Knockdown of Nampt expression was accompanied by lower levels of bronchoalveolar lavage (BAL) neutrophil infiltrates, total protein and TNF-α levels, as well as lower lung injury scores. Notably, Nampt knockdown was also associated with significantly increased BAL SFTPB levels relative to the wild-type control mice. Down-regulation of NAMPT increased the expression of SFTPB and rescued TNF-α-induced inhibition of SFTPB, whereas overexpression of NAMPT inhibited SFTPB expression in both H441 and A549 cells. Inhibition of NAMPT up-regulated SFTPB expression by enhancing histone acetylation to increase its transcription. Additional data indicated that these effects were mainly mediated by NAMPT nonenzymatic function via the JNK pathway. This study shows that pulmonary epithelial cell-specific knockdown of NAMPT expression attenuated ALI, in part, via up-regulation of SFTPB expression. Thus, epithelial cell-specific knockdown of Nampt may be a potential new and viable therapeutic modality to ALI.-Bi, G., Wu, L., Huang, P., Islam, S., Heruth, D. P., Zhang, L. Q., Li, D.-Y., Sampath, V., Huang, W., Simon, B. A., Easley, R. B., Ye, S. Q. Up-regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell-specific NAMPT knockdown.

STUDY OBJECTIVE: An increasing number of overweight and obese patients are presenting for ambulatory surgical procedures and may be at risk of complications including longer surgeries, longer length of stay (LOS), and possible increase in unanticipated return visits or hospital admissions. DESIGN: Observational study using prospectively-collected data. SETTING: Freestanding and hospital-based ambulatory surgery facilities. PATIENTS AND INTERVENTIONS: 13,957 patients underwent ambulatory cancer surgery procedures at the Josie Robertson Surgery Center (JRSC) since opening in 2016, and 4591 patients eligible for ambulatory surgery at JRSC underwent surgery at the main hospital during the same timeframe. MEASUREMENTS: We assessed whether BMI was associated with increased operative time, post-operative LOS, hospital transfer after surgery, or hospital readmission or urgent care center visits within 30 days. Using multivariable logistic regression, we assessed whether BMI was associated with decision to do surgery at JRSC controlling for age, ASA score and surgical service. MAIN RESULTS: While higher BMI was associated with a higher rate of transfer out of JRSC (p=0.014), the difference in rate was small (mean risk 0.8% for BMI 25 vs 1.3% for BMI 40, difference in risk 0.52%, 95% CI 0.05%, 1.0%). We found no evidence that higher BMI increased the risk of urgent care visits or readmissions within 30 days or outpatient LOS (p=0.7 for all). There was a statistically but not clinically significant difference in operative time for outpatient procedures (p =

BACKGROUND. Although ketorolac is an effective adjunct for managing pain in the perioperative period, it is associated with a risk of postoperative bleeding. This study retrospectively investigated the association between ketorolac use and both reoperation and postoperative opioid use among mastectomy patients. METHODS. The study identified all women undergoing mastectomy (unilaterally or bilaterally) at our ambulatory surgery cancer center from January 2016 to June 2019. The primary outcome was reoperation for bleeding on postoperative day 0 or 1, and the secondary outcome was postoperative opioid use. The association between ketorolac and outcomes was assessed using multivariable regression models. The covariates were age, body mass index, breast reconstruction, bilateral surgery, peripheral nerve block, and preoperative antiplatelet and/or anticoagulation medication. RESULTS. A cohort of 3469 women were identified. Ketorolac was given to 1549 (45 %) of the women, with 922 women (60 %) receiving 30 mg and 627 women (40 %) receiving 15 mg. The overall reoperation rate for bleeding was 3.1 % (1.8 % without ketorolac vs 4.8 % with ketorolac). In the multivariable analysis, ketorolac was associated with a higher risk of reoperation (odds ratio [OR], 2.43; 95 % confidence interval [CI], 1.60–3.70; P < 0.0001). Ketorolac also was associated with a lower proportion of patients receiving any postoperative narcotic within 24 h (15 mg: OR, 0.73; 95 % CI, 0.57–0.94; P = 0.014 vs 30 mg: OR, 0.52; 95 % CI, 0.42–0.66; P < 0.0001). CONCLUSIONS. Ketorolac use decreased postoperative opioid use, but this benefit was outweighed by the increased risk of bleeding requiring reoperation. This finding led to a change in practice at the authors’ center, with ketorolac no longer administered in the perioperative care of the mastectomy patient.

Purpose: The Centers for Medicare & Medicaid Services (CMS) identifies suboptimal management of treatment toxicities as a care gap and proposes the measurement of hospital performance on the basis of emergency department visits for 10 common symptoms. Current management strategies do not address symptom co-occurrence. Methods: We evaluated symptom co-occurrence in three patient cohorts that presented to a cancer hospital urgent care center in 2016. We examined both the CMS-identified symptoms and an expanded clinician-identified set defined as symptoms that could be safely managed in the outpatient setting if identified early and managed proactively. The cohorts included patients who presented with a CMS-defined symptom within 30 days of treatment, patients who presented within 30 days of treatment with a symptom from the expanded set, and patients who presented with a symptom from the expanded set within 30 days of treatment start. Symptom co-occurrence was measured by Jaccard index. A community detection algorithm was used to identify symptom clusters on the basis of a random walk process, and network visualizations were used to illustrate symptom dynamics. Results: There were 6,429 presentations in the CMS symptom-defined cohort. The network analysis identified two distinct symptom clusters centered around pain and fever. In the expanded symptom cohort, there were 5,731 visits and six symptom clusters centered around fever, emesis/nausea, fatigue, deep vein thrombosis, pain, and ascites. For patients who newly initiated treatment, there were 1,154 visits and four symptom clusters centered around fever, nausea/emesis, fatigue, and deep vein thrombosis. Conclusion: Uncontrolled symptoms are associated with unplanned acute care. Recognition of the complexity of symptom co-occurrence can drive improved management strategies.

IntroductionAn increasing proportion of cancer surgeries are ambulatory procedures requiring a stay of 1 day or less in the hospital. Providing patients and their caregivers with ongoing, real-time support after discharge aids delivery of high-quality postoperative care in this new healthcare environment. Despite abundant evidence that patient self-reporting of symptoms improves quality of care, the most effective way to monitor and manage this self-reported information is not known.Methods and analysisThis is a two-armed randomised, controlled trial evaluating two approaches to the management of patient-reported data: (1) team monitoring, symptom monitoring by the clinical team, with nursing outreach if symptoms exceed normal limits, and (2) enhanced feedback, real-time feedback to patients about expected symptom severity, with patient-activated care as needed.Patients with breast, gynaecologic, urologic, and head and neck cancer undergoing ambulatory cancer surgery (n=2750) complete an electronic survey for up to 30 days after surgery that includes items from a validated instrument developed by the National Cancer Institute, the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Information provided to patients in the Enhanced Feedback group is procedure-specific and based on updated PRO-CTCAE data from previous patients. Qualitative interviews are also performed. The primary study outcomes assess unplanned emergency department visits and symptom-triggered interventions (eg, nursing calls and pain management referrals) within 30 days, and secondary outcomes assess the patient and caregiver experience (ie, patient engagement, patient anxiety and caregiver burden).Ethics and disseminationThis study is approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center. The relationships between the study team and stakeholders will be leveraged to disseminate study findings. Findings will be relevant in designing future coordinated care models targeting improved healthcare quality and patient experience.Trial registration numberNCT03178045

OBJECTIVE Modern health care systems may be inadequately prepared for mass casualty respiratory failure requiring mechanical ventilation. Current health policy has focused on the "stockpiling" of emergency ventilators, though little is known about the performance of these ventilators under conditions of respiratory failure in adults and children. In this study, we seek to compare emergency ventilator performance characteristics using a test lung simulating pediatric lung injury. DESIGN Evaluation of ventilator performance using a test lung. SETTING Laboratory. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Six transport/emergency ventilators capable of adult/child application were chosen on the basis of manufacturer specifications, Autovent 3000, Eagle Univent 754, EPV 100, LP-10, LTV 1200, and Parapac 200D. Manufacturer specifications for each ventilator were reviewed and compared with known standards for alarms and functionality for surge capacity ventilators. The delivered tidal volume, gas flow characteristics, and airway pressure waveforms were evaluated in vitro using a mechanical test lung to model pediatric lung injury and integrated software. Test lung and flow meter recordings were analyzed over a range of ventilator settings. Of the six ventilators assessed, only two had the minimum recommended alarm capability. Four of the six ventilators tested were capable of being set to deliver a tidal volume of less than 200 mL. The delivered tidal volume for all ventilators was within 8% of the nominal setting at a positive end expiratory pressure of zero but was reduced significantly with the addition of positive end expiratory pressure (range, ±10% to 30%; p < .01). All ventilators tested performed comparably at higher set tidal volumes; however, only three of the ventilators tested delivered a tidal volume across the range of ventilator settings that was comparable to that of a standard intensive care unit ventilator. CONCLUSIONS Multiple ventilators are available for the provision of ventilation to children with respiratory failure in a mass casualty scenario. Few of these ventilators possess the minimum alarm functionality and consistently deliver the prescribed tidal volume that allows for safe and effective ventilation of critically ill pediatric patients. These findings will help clinicians understand the performance and limitations of available ventilators intended for use in children.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Advances in the treatment of patients with chronic pulmonary hypertension have greatly improved their functional status and longevity, and increasing numbers of these complex patients are presenting for elective noncardiac surgery. In this communication we will briefly review the classification and pathophysiology of pulmonary hypertension, summarize outpatient pharmacotherapy approaches, and discuss the perioperative preparation and management of these complex patients. With an understanding of the underlying pathophysiology of the disease and pharmacology of these new therapies, combined with careful perioperative planning and care, these patients can safely undergo elective surgical procedures.

Acute lung injury (ALI) in combination with acute kidney injury carries a mortality approaching 80% in the intensive care unit. Recently, attention has focused on the interaction of the lung and kidney in the setting of ALI and mechanical ventilation (MV). Small animal models of ALI and MV have demonstrated changes in inflammatory mediators, water channels, apoptosis, and function in the kidney early in the course of injury. The purpose of this investigation was to test the hypothesis that ALI and injurious MV cause early, measurable changes in kidney structure and function in a canine HCl aspiration model of ALI when hemodynamics and arterial blood gas tensions are carefully controlled. Intratracheal HCl induced profound ALI as demonstrated by increased shunt fraction and airway pressures compared with sham injury. Sham-injured animals had similar mean arterial pressure and arterial Pco2 and HCO3 levels compared with injured animals. Measurements of renal function including renal blood flow, urine flow, serum creatinine, glomerular filtration rate, urine albumin-to-creatinine ratio, and kidney histology scores were not different between groups. With maintenance of hemodynamic parameters and alveolar ventilation, ALI and injurious MV do not alter kidney structure and function early in the course of injury in this acid aspiration canine model. Kidney injury in large animal models may be more similar to humans and may differ from results seen in small animal models.

The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, the MIF gene and protein expression were examined in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. MIF gene expression and protein levels were significantly increased in each ALI model, with serum MIF levels significantly higher in patients with either sepsis or ALI compared with healthy controls (African- and European-descent). The association of 8 MIF gene polymorphisms (single-nucleotide polymorphisms (SNPs)) (within a 9.7-kb interval on chromosome 22q11.23) with the development of sepsis and ALI in European-descent and African-descent populations was studied next. Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3' end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.

The study of lung mechanics has progressed from global descriptions of lung pressure and volume relationships to the high-resolution, three-dimensional, quantitative measurement of dynamic regional mechanical properties and displacements. X-ray computed tomography (CT) imaging is ideally suited to the study of regional lung mechanics in intact subjects because of its high spatial and temporal resolution, correlation of functional data with anatomic detail, increasing volumetric data acquisition, and the unique relationship between CT density and lung air content. This review presents an overview of CT measurement principles and limitations for the study of regional mechanics, reviews some of the early work that set the stage for modern imaging approaches and impacted the understanding and management of patients with acute lung injury, and presents evolving novel approaches for the analysis and application of dynamic volumetric lung image data.

Venegas, José G., R. Scott Harris, and Brett A. Simon.A comprehensive equation for the pulmonary pressure-volume curve. J. Appl. Physiol. 84(1): 389–395, 1998.—Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and may lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = a + b[1 +[Formula: see text]]−1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs ( n = 9), oleic acid-induced acute respiratory distress syndrome ( n = 2), and mechanically ventilated patients with acute respiratory distress syndrome ( n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, cto the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient ( R 2) of 0.997 ± 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V − a)/ bvs. (P − c)/ d, they collapsed into a single and tight relationship ( R 2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters.

We report the use of high-frequency oscillatory ventilation in the operating room during repair of multiple bronchopleural fistulae in a 9-year-old boy. In addition, we used principles of permissive hypercapnia to further minimize barotrauma. There were no cardiovascular consequences due to either the high-frequency ventilation or the permissive hypercapnia. Our goals in employing this strategy were to minimize barotrauma, minimize gas flow through the fistulae, and optimize the surgical results.

This review provides a summary of pulmonary functional imaging approaches for determining pulmonary ventilation, with a specific focus on multi-detector x-ray computed tomography and magnetic resonance imaging (MRI). We provide the important functional definitions of pulmonary ventilation typically used in medicine and physiology and discuss the fact that some of the imaging literature describes gas distribution abnormalities in pulmonary disease that may or may not be related to the physiological definition or clinical interpretation of ventilation. We also review the current state-of-the-field in terms of the key physiological questions yet unanswered related to ventilation and gas distribution in lung disease. Current and emerging imaging research methods are described, including their strengths and the challenges that remain to translate these methods to more wide-spread research and clinical use. We also examine how computed tomography and MRI might be used in the future to gain more insight into gas distribution and ventilation abnormalities in pulmonary disease.

Objective: The Sensormedics 3100A and 3100B are widely used to provide high-frequency oscillatory ventilation in clinical practice. Infants and children 35 kg with the 3100B. This study compares the effect of ventilator and patient parameters on delivered tidal volume during high-frequency oscillatory ventilation of a test lung with these devices. Design: Laboratory-based study. Subjects: Test lung and Sensormedics 3100A and 3100B highfrequency oscillators. Interventions: A previously validated hot-wire flowmeter (Florian) was placed in series with either a 3100A (n 3) or 3100B (n 3) ventilator and a Michigan test lung. Tidal volumes were measured over a range of mean airway pressure, inspiratory:expiratory ratio, frequency, pressure amplitude, and endotracheal tube internal diameter. Measurements and Main Results: The 3100A and 3100B delivered similar tidal volumes across a range of ventilator parameters for an inspiratory:expiratory ratio of 1:1, differing by

A difficult airway caused by mechanical obstruction from dislodged spinal hardware in a patient undergoing revision surgery for a cervical chordoma is presented. Due to the logical, sequential multidisciplinary airway and patient management by the anesthesiology, neurosurgery, and otolaryngology teams working together in an environment of clear communication, a potential life-threatening crisis was averted with successful outcome for the patient.

OBJECTIVEThe purpose of this study was to determine the applicability, safety, and normal parameters of a xenon-enhanced CT technique to quantify maxillary sinus ventilation.PATIENTS AND METHODSNine healthy subjects inhaled a xenon-oxygen-air mixture through their noses while repeated CT scans were performed through the same section of their sinuses. Images were obtained every 1 to 3 minutes and analyzed to measure the density of the gas in the maxillary sinus as a function of time.RESULTSIndividual nasal cavity time constants ranged from 0.5 to 18 minutes. Studies performed after decongestion showed poorer sinus ventilation.CONCLUSIONSThe xenon-CT washin/washout technique is safe, effective, and gives representative data.

a) Characterize how ventilator and patient variables affect tidal volume during high-frequency oscillatory ventilation; and b) measure tidal volumes in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation.Observational study.Research laboratory and medical intensive care unit.Test lung and patients with acute respiratory distress syndrome.Using a previously validated hot wire anemometer placed in series with a Sensormedics 3100B high-frequency ventilator, an endotracheal tube, and a test lung, tidal volume was measured at different combinations of frequency (4, 6, 8, 10, and 12 Hz), pressure amplitude (50, 60, 70, 80, and 90 cm H2O), mean airway pressure (20, 30, and 40 cm H2O), test lung compliance (10, 30, and 50 mL/cm H2O), endotracheal tube internal diameter (6, 7, and 8 mm), bias flow (20, 30, and 40 L/min), and inspiratory/expiratory ratio (1:2 and 1:1). In patients, tidal volume was measured at baseline ventilator settings and at baseline frequency +/-2 Hz and baseline pressure amplitude +/-10 cm H2O.Measured tidal volumes were 23-225 mL during high-frequency oscillatory ventilation of the test lung. A 2-Hz increase in frequency and a 10-cm H2O increase in pressure amplitude caused a 21.3% +/- 4.1% decrease and 21.4% +/- 3.4% increase in tidal volume, respectively. Decreasing endotracheal tube internal diameter from 8 mm to 7 mm and from 7 mm to 6 mm caused a 15.3% +/- 1.7% and 18.9% +/- 2.1% reduction in tidal volume, respectively. Increasing bias flow from 20 L/min to 30 L/min increased tidal volume by 11.2% +/- 3.9%. Further increases in bias flow, changes in compliance, and changes in mean airway pressure had little effect. Tidal volumes measured in acute respiratory distress syndrome patients were 44-210 mL. A 2-Hz increase in frequency was associated with a 23.1% +/- 6.3% decrease in tidal volume. In contrast to the test lung data, a 10-cm H2O increase in pressure amplitude resulted in only a 5.6% +/- 4.5% increase in tidal volume.Tidal volumes are not uniformly small during high-frequency oscillatory ventilation. The primary determinant of tidal volume in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation with the Sensormedics 3100B is frequency. Test lung findings suggest that endotracheal tube internal diameter is also an important determinant of tidal volume.

Objective Assess the accuracy of four different methods of measuring tidal volume during simulated high-frequency oscillatory ventilation. Design In vitro study. Setting Research laboratory. Subjects Three differential pressure pneumotachometers, a modified Pitot tube, an ultrasound flowmeter, and an adult hot wire anemometer. Interventions Each device was placed in series with a Sensormedics 3100B high-frequency ventilator and an 8.0-mm endotracheal tube attached to a 48.9-L plethysmograph. Inspiratory/expiratory ratio was fixed at 1:1 and mean airway pressure at 10 cm H2O. Tidal volumes were calculated at each combination of frequency (f: 3, 4, 6, 8, 10, 12 Hz) and pressure amplitude (DeltaP: 30, 60, 90 cm H2O) by digital integration of the sampled flow signals from each device and compared with those calculated from pressure changes within the plethysmograph. The protocol was repeated after incorporation of frequency-specific calibrations to the flow-measuring algorithm of each device. The hot wire anemometer was further evaluated at Fio2 of 1.0, 37 degrees C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. Measurements and main results Tidal volumes were 36-305 mL. Bland-Altman analysis demonstrated that each device exhibited systematic bias before frequency-specific adjustment. After frequency-specific adjustment of the flow-measuring algorithm, the two most accurate and precise devices were the Hans Rudolph pneumotachometer, which exhibited a mean error of 0.2% (95% confidence interval, -3.0% to 3.4%), and the hot wire anemometer, which had a mean error of -1.1% (95% confidence interval, -5.5% to 3.3%). The hot wire anemometer remained accurate at Fio2 1.0, 37 degrees C, 80% humidity, mean airway pressure of 20 cm H2O, and an inspiratory/expiratory ratio of 1:2. Conclusions Tidal volume can be measured during high-frequency oscillatory ventilation using a variety of techniques. Frequency-specific calibration improves the accuracy and precision of tidal volume measurements. Hot wire anemometry exhibits stable performance characteristics across the range of temperature, humidity, Fio2, and inspiratory/expiratory ratios encountered clinically, has a small deadspace, is unaffected by mean airway pressure, and is therefore suitable for clinical applications.

During our previous attempt to search for the candidate genes to acute lung injury (ALI), we unexpectedly identified PBEF as the most highly upregulated gene in a canine model of ALI by crosshybridizing canine lung cRNA to the Affymetrix human gene chip HG-U133A. The result suggested that PBEF may be a potential biomarker in ALI. To extend and translate that finding, we have performed the molecular cloning and characterization of canine PBEF cDNA in this study. Deduced amino acid sequence alignment revealed that the PBEF gene is evolutionarily highly conserved, with the canine PBEF protein sequence 96% identical to human PBEF and 94% identical to both murine and rat PBEF counterparts. Canine PBEF protein was successfully expressed both by in vitro transcription coupled with translation in a cell-free system and by transfection of canine PBEF cDNA into the human lung type II alveolar adenocarcinoma cell line A549. The expressed canine PBEF protein was visualized by either an anti-V5 tag peptide polyclonal antibody or an anti-canine PBEF peptide polyclonal antibody. RT-PCR assay indicates that canine PBEF is expressed in canine lung, brain, heart, liver, spleen, kidney, pancreas, and muscle, with liver showing the highest expression,followed by muscle. Isolation of the canine PBEF cDNA and expression of its recombinant protein may provide molecular tools to study the molecular mechanism of ALI in the canine model and to elucidate the potential role of PBEF as an ALI biomarker.

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.

Background Genomic approaches in large animal models (canine, ovine etc) are challenging due to insufficient genomic information for these species and the lack of availability of corresponding microarray platforms. To address this problem, we speculated that conserved interspecies genetic sequences can be experimentally detected by cross-species hybridization. The Affymetrix platform probe redundancy offers flexibility in selecting individual probes with high sequence similarities between related species for gene expression analysis. Results Gene expression profiles of 40 canine samples were generated using the human HG-U133A GeneChip (U133A). Due to interspecies genetic differences, only 14 ± 2% of canine transcripts were detected by U133A probe sets whereas profiling of 40 human samples detected 49 ± 6% of human transcripts. However, when these probe sets were deconstructed into individual probes and examined performance of each probe, we found that 47% of human probes were able to find their targets in canine tissues and generate a detectable hybridization signal. Therefore, we restricted gene expression analysis to these probes and observed the 60% increase in the number of identified canine transcripts. These results were validated by comparison of transcripts identified by our restricted analysis of cross-species hybridization with transcripts identified by hybridization of total lung canine mRNA to new Affymetrix Canine GeneChip®. Conclusion The experimental identification and restriction of gene expression analysis to probes with detectable hybridization signal drastically increases transcript detection of canine-human hybridization suggesting the possibility of broad utilization of cross-hybridizations of related species using GeneChip technology.

Efforts to establish a quantitative approach to the computed tomography (CT)-based character ization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function.Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging.Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching.With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment–derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [18F]fluoro-2-deoxy-D-glucose.

Disease of the paranasal sinuses is a common and costly condition. Evaluation of the efficacy of either medical or surgical methods of treatment is limited by the lack of quantitative methods to characterize sinus ventilation, which may be an important determinant of the baseline physiological state of the sinuses. Xenon-enhanced computed tomography (Xe-ct) measurement of sinus ventilation provides a noninvasive method of quantifying maxillary sinus ventilation using the nonradioactive, radiodense gas Xe as a tracer. Study subjects breathed a mixture of Xe gas and oxygen through a close-fitting nasal mask during serial ct imaging of a single radiographic plane through the maxillary sinuses — a generally well-tolerated protocol. Analysis of the sinus density–time curves allowed calculation of first-order exponential time constants from which specific ventilation rates could be determined for individual sinuses. Previously developed data analysis techniques were used to assess the statistical significance of the data and determine confidence intervals, allowing examination of the effects of noise in the data, and to demonstrate areas for further study protocol refinement. We conclude that Xe-ct measurement of sinus ventilation is a potentially valuable noninvasive technique for the diagnostic imaging of the human maxillary sinus.

Heterogeneity of regional lung mechanics is an important determinant of the work of breathing and may be a risk factor for ventilator associated lung injury. The ability to accurately assess heterogeneity may have important implications for monitoring disease progression and optimizing ventilator settings. Inverse modeling approaches, when applied to dynamic pulmonary impedance data (Z(L)), are thought to be sensitive to the detection of mechanical heterogeneity with the ability to characterize global lung function using a minimal number of free parameters. However, the reliability and bias associated with such model-based estimates of heterogeneity are unknown. We simulated Z(L) spectra from healthy, emphysematous, and acutely injured lungs using a computer-generated anatomic canine structure with asymmetric Horsfield branching and various predefined distributions of stochastic lung tissue heterogeneity. Various inverse models with distinct topologies incorporating linear resistive and inertial airways with parallel tissue viscoelasticity were then fitted to these Z(L) spectra and evaluated in terms of their quality of fit as well as the accuracy and reliability of their respective model parameters. While all model topologies detected appropriate changes in tissue heterogeneity, only a topology consisting of lumped airway properties with distributed tissue properties yielded accurate estimates of both mean lung tissue stiffness and the spread of regional elastances. These data demonstrate that inverse modeling approaches applied to noninvasive measures of Z(L) may provide reliable and accurate assessments of lung tissue heterogeneity as well as insight into distributed lung mechanical properties.