Nebulized caffeine alleviates airway hyperresponsiveness in a murine asthma model.

The clinical definition of "difficult asthma" has expanded recently to include an ever-growing subset of patients with symptoms that cannot be controlled by conventional means, forcing the medical community to develop innovative therapeutics. Beneficial effects of coffee for subjects with asthma, primarily the effect of methylxanthine components, have long been described. Methylxanthines, including theophylline and caffeine, inhibit phosphodiesterases and downstream cAMP signaling to prevent mast cell degranulation while promoting immunomodulation (Peleman RA, Kips JC, Pauwels RA. Clin Exp Allergy 28: 53-56, 1998; Deshpande DA, Wang WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK, Liggett SB. Nat Med 16: 1299-1304, 2010). Caffeine is also a bitter taste receptor agonist, binding to taste-sensing type 2 receptors (TAS2R) before releasing calcium to hyperpolarize airway smooth muscle membranes, inducing bronchodilation (Workman AD, Palmer JN, Adappa ND, Cohen NA. Curr Allergy Asthma Rep 15: 72, 2015; Devillier P, Naline E, Grassin-Delyle S. Pharmacol Ther 155: 11-21, 2015). Theophylline is conventionally used to treat asthma, whereas, according to the literature, the dosage required for orally administered caffeine has yielded modest improvement (Alfaro TM, Monteiro RA, Cunha RA, Cordeiro CR. Clin Respir J 12: 1283-1294, 2018). We sought to determine whether aerosolization of ultrafine caffeine particles (2.5-4 µm) directly to the lungs of susceptible A/J mice challenged with methacholine would improve pulmonary function via forced oscillation technique. In addition, we assessed whether nebulization of caffeine leads to changes in lung pathophysiology and bronchoalveolar lavage cell profiles. We found that mice that received aerosolized caffeine had statistically significant decreases in maximum airway resistance [6.3 vs. 3.9 cmH2O·s/mL at 62.5 mg/mL caffeine; confidence interval (CI) = -4.3, -0.4; P = 0.02] and significant delays in the time required to reach maximum resistance compared with that of controls (64.7 vs. 172.1 sec at 62.5 mg/mL caffeine, CI = 96.0, 118.9; P < 0.0001). Nebulized caffeine yielded a consistent effect on airway hyperresponsiveness at a range of doses without evidence of significant pathology relative to vehicle control.NEW & NOTEWORTHY For decades, coffee has been shown to improve symptoms in patients with asthma. One component, theophylline, is conventionally used to treat asthma, whereas the dosage required for orally administered caffeine has yielded modest improvement. We sought to determine whether aerosolization of caffeine directly to the lungs of susceptible A/J mice challenged with methacholine would alter pulmonary function via forced oscillation technique. We found nebulized caffeine yielded a consistent improvement on murine AHR.

The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR.

The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated OR2W3 caused increases in [Ca2+]i and relaxation of ASM cells. Of note, OR2W3-evoked [Ca2+]i mobilization and ASM relaxation required Ca2+ flux through the store-operated calcium entry (SOCE) pathway and accompanied plasma membrane depolarization. This chemosensory odorant receptor response was not mediated by adenylyl cyclase (AC)/cyclic nucleotide-gated (CNG) channels or by protein kinase A (PKA) activity. Instead, ASM olfactory responses to the monoterpene nerol were predominated by the activity of Ca2+-activated chloride channels (TMEM16A), including the cystic fibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum. These findings demonstrate compartmentalization of Ca2+ signals dictates the odorant receptor OR2W3-induced ASM relaxation and identify a previously unrecognized E-C coupling mechanism that could be exploited in the development of therapeutics to treat obstructive lung diseases.

Pediatric Difficult Airway Response Team Utilization in the Emergency Department: A Case Series.

OBJECTIVES: A multidisciplinary pediatric difficult airway team was created at our institution to respond to hospital-wide airway emergencies. We report the characteristics, indications, and outcomes of these activations that occur in the pediatric emergency department (PED). METHODS: Retrospective, single-center cohort study comprised all difficult airway team activations occurring in the PED from the program's inception in 2008 to 2018. Ages of ≤18 years were included. For each case, detailed information was abstracted, including patient factors, PED context and milieu, airway interventions, and airway outcomes. RESULTS: There were 15 difficult airway response team activations in the PED during the study period, or 1.4 activations per year. The most common indications for activation were contaminated airways (n = 7; 47%) and history of difficult intubation (n = 4; 27%). Definitive airway management was successful in all cases, except for a single case where intervention was unnecessary. The most commonly performed definitive airway intervention was direct laryngoscopy (n = 6; 40%). There were no instances of emergency front-of-neck access. CONCLUSIONS: Difficult airways in the PED were uncommon. Most cases were resolved with familiar equipment including direct laryngoscopy, video laryngoscopy, and supraglottic airways.

Age-Related Changes in Upper Airway Anatomy Via Ultrasonography in Pediatric Patients.

PURPOSE: Ultrasonography is a portable, noninvasive tool that may be used to evaluate the upper airway. The purpose of our study was to present a systematic approach to identify salient features of the pediatric airway and determine whether ultrasonography can identify anatomical changes that occur with growth and development. METHODS: We present a prospective, observational trial where patients included were between 1 day and 10 years of age presenting for elective surgery who had no known history of unfavorable airway pathology. We sequentially obtained 5 ultrasound views under anesthesia: (1) sagittal sternal notch view of the trachea, (2) sagittal longitudinal view of trachea (LT), (3) axial view at the level of the vocal cords (AVC), (4) axial view at the level of the cricoid membrane (AC), and (5) sagittal longitudinal submental space view (SM). A broadband linear array transducer was used to identify airway structures and perform measurements. RESULTS: Eighty-four percent of enrolled patients underwent airway imaging and were analyzed using multiple regression and Spearman correlation (ρ). In view 1, tracheal diameter via sagittal sternal notch view was immeasurable because of air disturbance. In the LT view, the distance from the skin to the cricothyroid membrane (LT1) did not statistically increase with age in days (P = 0.06); however, the distance from the cricoid to thyroid cartilage (LT2) did correlate to age (P < 0.001; 99% confidence interval [CI], 1.8 × 10-5, 7.7 × 10-5; ρ = 0.77, P = 0.001). We found a statistically significant relationship between age and the distance between the anterior and posterior commissures (AVC2; P < 0.001; 99% CI, 1.0 × 10-4, 1.7 × 10-4; ρ = 0.80, P < 0.001), the distance from the skin to the posterior commissure (AVC3; P < 0.001; 99% CI, 9.6 × 10-5, 2.0 × 10-4; ρ = 0.73, P < 0.001), the distance to the cricoid cartilage (AC; P < 0.001; 99% CI, 2.0 × 10-5, 7.7 × 10-5; ρ = 0.66, P < 0.001), and the distance from the tongue base to the soft palate (SM2; P < 0.001; 9% CI, 1.8 × 10-4, 3.9 × 10-4; ρ = 0.85, P < 0.001). There were no significant relationships between age and AVC1 (P = 0.16) and SM1 (P = 0.44). CONCLUSIONS: Airway ultrasound is a feasible tool to evaluate the pediatric airway in children younger than 10 years; however, the detection of age-related changes of certain structures is limited to select measurements.

Laryngoscopy Grade Improvement and Difficult Airway Resolution in Infants With Robin Sequence Undergoing Mandibular Distraction Osteogenesis: A Multi-Institutional Study.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) aims to relieve tongue-based airway obstruction in Robin Sequence (RS). We investigated direct laryngoscopy grade (DLG) improvement and difficult airway (DA) resolution following MDO. DESIGN: Retrospective cohort analysis. SETTING: Three tertiary care institutions. PATIENTS: Sixty-four infants with RS who underwent a single MDO procedure in their first year of life were identified from January 2010 to January 2019. MAIN OUTCOME MEASURES: The primary outcome was DLG pre- and post-MDO. Secondary outcomes included DA designation, pre- and post-MDO polysomnographic assessment for obstructive sleep apnea (OSA), length of stay, need for gastrostomy, and major/minor adverse events. RESULTS: Median DLG improved from II pre-MDO to I at the time of distractor removal (n = 43, P < .001). No significant change was seen in patients with a third recorded time point (eg, palatoplasty; n = 78, P = .52). Twenty-six (47%) of 55 patients were designated as DA pre-MDO, and 10 (18%) of 55 patients retained the label post-MDO (P < .01). Five (50%) of these 10 patients appeared to be inappropriately retained. Median obstructive apnea-hypopnea index improved from 38.6 (range 31.2-62.8) pre-MDO to 2.9 (range 1-3.9) post-MDO (n = 12; P = .002). CONCLUSION: Mandibular distraction osteogenesis allowed for DLG improvement that was stably maintained as well as functional improvement in OSA, with minimal morbidity. Difficult airway designation persisted in the electronic record of some infants despite clinical resolution.

Effects of Obstructive Sleep Apnea and Obesity on Morphine Pharmacokinetics in Children.

BACKGROUND: Obesity increases susceptibility to chronic pain, increases metabolism, and is associated with obstructive sleep apnea syndrome (OSAS), all which can complicate perioperative pain management of patients. In addition, obesity and OSAS can cause elevation of the adipose-derived hormone leptin, which increases metabolism. We hypothesized that obesity along with sleep apnea and leptin independently enhance morphine pharmacokinetics. METHODS: Children 5-12 years of age who were presenting for surgery were administered a morphine dose of 0.05 mg/kg. Blood was collected at baseline and at subsequent preset times for pharmacokinetic analysis of morphine and its metabolites. Three groups were studied: a nonobese group with severe OSAS, an obese group with severe OSAS, and a control group. RESULTS: Thirty-four patients consisting of controls (n = 16), nonobese/OSAS (n = 8), and obese/OSAS (n = 10) underwent analysis. The obese/OSAS group had a higher dose-adjusted mean maximum morphine concentration (CMAX) over 540 minutes compared to the controls (P < .001) and those with only OSAS (P = .014). The obese/OSAS group also had lower volume of distribution (Vd) when compared to OSAS-only patients (P = .007). In addition, those in the obese/OSAS group had a higher morphine 3-glucuronide (M3G) maximum concentration (P = .012) and a higher ratio of M3G to morphine than did the control group (P = .011). Time to maximum morphine 6-glucuronide (M6G) concentration was significantly lower in both nonobese/OSAS and obese/OSAS groups than in the control group (P < .005). C-reactive protein (CRP), interleukin (IL)-10, and leptin were all higher in the obese/OSAS group than in controls (P = .004, 0.026, and <0.001, respectively), and compared to OSAS-only patients, CRP (P = .013) and leptin (P = .002) levels were higher in the obese/OSAS group. CONCLUSIONS: The combination of obesity and OSAS was associated with an increase in morphine metabolism compared with that in normal-weight controls. Our previous study in mice demonstrated that obesity from leptin deficiency decreased morphine metabolism, but that metabolism normalized after leptin replacement. Leptin may be a cause of the increased morphine metabolism observed in obese patients.

Impact of Clinical Guidelines on Revisits After Ambulatory Pediatric Adenotonsillectomy.

BACKGROUND: Pediatric adenotonsillectomies are common and carry known risks of potentially severe complications. Complications that require a revisit, to either the emergency department or hospital readmission, increase costs and may be tied to lower reimbursements by federal programs. In 2011 and 2012, recommendations by pediatric and surgical organizations regarding selection of candidates for ambulatory procedures were issued. We hypothesized that guideline-associated changes in practice patterns would lower the odds of revisits. The primary objective of this study was to assess whether the odds of a complication-related revisit decreased after publication of guidelines after accounting for preintervention temporal trends and levels. The secondary objective was to determine whether temporal associations existed between guideline publication and characteristics of the ambulatory surgical population. METHODS: This study employs an interrupted time series design to evaluate the longitudinal effects of clinical guidelines on revisits. The outcome was defined as revisits after ambulatory tonsillectomy for privately insured patients. Data were sourced from the Truven Health Analytics MarketScan database, 2008-2015. Revisits were defined by the most prevalent complication types: hemorrhage, dehydration, pain, nausea, respiratory problem, infection, and fever. Time periods were defined by surgeries before, between, and after guidelines publication. Unadjusted odds ratios estimated associations between revisits and clinical covariates. Multivariable logistic regression was used to estimate the impact of guidelines on revisits. Differences in revisit trends among pre-, peri-, and postguideline periods were tested using the Wald test. Results were statistically significant at P < .005. RESULTS: A total of 326,993 surgeries met study criteria. The absolute revisit rate increased over time, from 5.9% (95% confidence interval [CI], 5.8-6.0) to 6.7% (95% CI, 6.6-6.9). The proportion of young children declined slightly, from 6.4% to 5.9% (P < .001). The proportion of patients having a tonsillectomy in an ambulatory surgery center increased (16.5%-31%; P < .001), as did the prevalence of obstructive sleep apnea (7.0%-14.0%; P < .001) and sleep-disordered breathing (20.6%-35.0%; P < .001). In a multivariable logistic regression model adjusted for age, sex, comorbidities, and surgical location, odds of a revisit increased during the preguideline period (0.4% increase per month; 95% CI, 0.24%-0.54%; P < .001). This monthly increase did not continue after guidelines (P = .002). CONCLUSIONS: While odds of a postoperative revisit did not decline after guideline publication, there was a significant difference in trend between the pre- and postguideline periods. Changes in the ambulatory surgery population also suggest at least partial adherence to guidelines.

Perioperative outcomes and management in midface advancement surgery: a multicenter observational descriptive study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND/AIMS: The evolution of Le Fort III and Monobloc procedures with utilization of distraction devices has resulted in shortened surgical times, greater facial advancements, and decreased transfusion requirements. The aim of this observational study was to utilize data from the multicenter Pediatric Craniofacial Surgery Perioperative Registry to present and compare patient characteristics and outcomes in children undergoing midface advancement with distraction osteogenesis. METHODS: We queried the Pediatric Craniofacial Surgery Perioperative Registry for children undergoing midface advancement involving distractor application from June 2012 to September 2016. Data extracted included demographics, perioperative management, complications, fluid and transfusion volumes, and length of stay. The extracted patient characteristics and perioperative variables were summarized and compared. RESULTS: The query yielded 72 cases from 11 institutions: 49 children undergoing Le Fort III and 23 undergoing Monobloc procedures. Monobloc patients were younger, weighed less, and more likely to have tracheostomies along with elevated intracranial pressure. Greater transfusion was observed in the Monobloc group for nearly all of the transfusion outcomes evaluated. Median ICU and hospital length of stay were 2 and 3 days longer, respectively, in the Monobloc group. Perioperative complications were not uncommon, occurring in 18% of patients in the Le Fort III group and 30% in the Monobloc group. CONCLUSION: Monobloc procedures were associated with greater transfusion and longer ICU and hospital length of stay. Perioperative complications were more prevalent in the Monobloc group.

Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model.

BACKGROUND: Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. METHODS: Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy. WT mice received several dosing regimens of morphine. Obese mice (30 g) received one 80 mg/kg bolus of morphine. Blood was collected at fixed times after morphine injection for quantification of plasma morphine and morphine 3-glucuronide (M3G) levels. PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2). PK parameters were compared between mouse groups by the use of 1-way analysis of variance, with P values less than .05 considered significant. RESULTS: DIO compared with WT mice had significantly decreased morphine metabolism with lower M3G-to-morphine ratio (mean difference [MD]: -4.9; 95% confidence interval [CI]: -8.8 to -0.9) as well as a decreased Cl/F (MD: -4.0; 95% CI: -8.9 to -0.03) Ob/ob compared with WT mice had a large increase in morphine exposure with a greater AUC150 (MD: 980.4; 95% CI: 630.1-1330.6), CMAX (MD: 6.8; 95% CI: 2.7-10.9), and longer T1/2 (MD: 23.1; 95% CI: 10.5-35.6), as well as a decreased Cl/F (MD: -7.0; 95% CI: -11.6 to -2.7). Several PK parameters were significantly greater in ob/ob compared with DIO mice, including AUC150 (MD: 636.4; 95% CI: 207.4-1065.4), CMAX (MD: 5.3; 95% CI: 3.2-10.3), and T1/2 (MD: 18.3; 95% CI: 2.8-33.7). When leptin was replaced in ob/ob mice, PK parameters began to approach DIO and WT levels. LR compared with ob/ob mice had significant decreases in AUC150 (MD: -779.9; 95% CI: -1229.8 to -330), CMAX (MD: -6.1; 95% CI: -11.4 to -0.9), and T1/2 (MD: -19; 95% CI: -35.1 to -2.8). Metabolism increased with LR, with LR mice having a greater M3G-to-morphine ratio compared with DIO (MD: 5.3; 95% CI: 0.3-10.4). CONCLUSIONS: Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.

Are nocturnal hypoxemia and hypercapnia associated with desaturation immediately after adenotonsillectomy?

BACKGROUND: Children who undergo adenotonsillectomy for sleep-disordered breathing frequently have postoperative oxygen desaturations. Nocturnal hypoxia has been shown to predict postoperative respiratory complications; however, other gas exchange abnormalities detected on polysomnography (PSG) have not been evaluated. AIM: We sought to determine whether hypercapnia seen on preoperative nocturnal PSG can predict postoperative hypoxemia. METHODS: We conducted a retrospective review of 319 children who underwent polysomnography before adenotonsillectomy. Saturation levels were recorded for at least 2 h postoperatively, and the primary outcome was desaturation (<90%). RESULTS: The median patient age was 5 years (range, 5 months-17 years). Patients who desaturated postoperatively had higher median peak endtidal CO2 (EtCO2 ) levels (55.5 vs 52 mmHg; P = 0.02), lower saturation nadirs (80.5% vs 88%; P = 0.048), and were younger (2 vs 6 years; P < 0.001) than those without desaturation. Age was significantly correlated with peak EtCO2 (r = -0.16), respiratory disturbance index (RDI; r = -0.23), and oxygen saturation nadir (r = 0.25; all P < 0.01). In unadjusted analysis, age <3 years compared to ≥9 years (odds ratio [OR] = 10.09; 95% confidence interval [CI] = 2.13-96.26), peak EtCO2  > 55 mmHg (OR = 3.38; 95% CI = 1.21-9.47), and RDI ≥ 10 (OR = 2.89; 95% CI = 1.05-8.42) were associated with increased odds of desaturation. Multivariable logistic regression on age, race, sex, peak EtCO2 , RDI, opioid use, and saturation nadir showed that only age was significantly associated with postoperative desaturation. Patients 0-2 years old were 10.43 (95% CI = 1.89-110.9) times more likely to have desaturation than patients 9-17 years old. CONCLUSION: Patients <3 years of age are most likely to have postoperative hypoxemia after adenotonsillectomy. Gas exchange abnormalities did not correlate with postoperative desaturations, although age and peak EtCO2 did strongly correlate.

ACE2 and TAS2R38 receptor expression in pediatric and adult patients in the nasal and oral cavity.

Objective: To investigate differences in angiotensin-converting-enzyme-2 (ACE2) and bitter taste receptor (TAS2R38) expression between patient age groups and comorbidities to characterize the pathophysiology of coronavirus 19(COVID-19) pandemic. ACE2 is the receptor implicated to facilitate SARS-CoV-2 infections and levels of expression may correlate to the severity of COVID-19 infection. TAS2R38 has many non-gustatory roles in disease, with some evidence of severe COVID-19 disease in certain receptor phenotypes. Methods: We conducted a prospective cohort study and collected nasal and lingual tissue from healthy pediatric (n = 22) and adult (n = 25) patients undergoing general anesthesia for elective procedures. RNA isolation and qPCR were performed with primers targeting ACE2 and TAS2R38. Results: A total of 25 adult (52% male; 44% obese) and 22 pediatric (50% male; 36% obese) patients were enrolled, pediatric tissue had 43% more nasal ACE2 RNA expression than adults with a median fold change of 0.69 (IQR 0.37, 0.98) in adults and 0.99 (IQR 0.74, 1.43) in children (p < .05). There were no differences between the age groups in ACE2 expression of lingual tissue (p = .14) or TAS2R38 expression collected from either nasal (p = 049) or lingual tissue (p = .49). Stratifying for obesity yielded similar differences between nasal ACE2 expression between adults and children with median fold change of 0.56 (IQR 0.32, 0.87) in adults and 1.0 (IQR 0.82, 1.52) in children (p < .05). Conclusions: ACE2 receptor expression is higher in nasal tissue collected from children compared to adults, suggesting COVID-19 infectivity is more complicated than ACE2 and TAS2R38 mRNA expression. Level of Evidence: NA.

Computer-aided design and manufacturing in craniosynostosis surgery.

BACKGROUND: Considerable operative time is expended during the planning, shaping, and reconfiguring of the cranial vault in the pursuit of symmetry during open craniosynostosis surgery. Computer-aided design and manufacturing has recently been implemented in orthognathic surgery and complex craniomaxillofacial reconstruction as a means of optimizing operative accuracy and efficiency. In this report, we highlight our growing experience with this promising modality for the preoperative planning and intraoperative execution of cranial vault remodeling in patients with both simple and complex forms of craniosynostosis. METHODS: Computer-assisted surgical planning begins with acquisition of high-resolution computed tomography scans of the craniofacial skeleton. An Internet-based teleconference is then held between the craniofacial and biomedical engineering teams and provides a forum for virtual manipulation of the patient's preoperative three-dimensional computed tomography with real-time changes and feedback. Through virtual surgical planning, osteotomies are designed and calvarial bones reconfigured to achieve the desired cranial vault appearance. Cutting and positioning guides are manufactured to transform the virtual plan into a reality. RESULTS: From February to March 2012, 4 children (aged 9 months to 6 years) with craniosynostosis underwent computer-assisted simulation and surgery. Diagnoses included metopic, unicoronal (n = 2), and multisutural synostoses (sagittal and left unicoronal). Open craniofacial repairs were performed as virtually planned, including front o-orbital remodeling, fronto-orbital advancement, and anterior two-thirds calvarial remodeling, respectively. Cutting and final positioning guides demonstrated excellent fidelity and ease of use. CONCLUSIONS: Computer-aided design and manufacturing may offer a platform for optimizing operative efficiency, precision, and accuracy in craniosynostosis surgery, while accelerating the learning curve for future trainees.

Factors Associated With Pediatric Emergency Airway Management by the Difficult Airway Response Team.

Background The goal of this study was to determine if difficult airway risk factors were similar in children cared for by the difficult airway response team (DART) and those cared for by the rapid response team (RRT). Methods In this retrospective database analysis of prospectively collected data, we analyzed patient demographics, comorbidities, history of difficult intubation, and intubation event details, including time and place of the emergency and devices used to successfully secure the airway. Results Within the 110-patient cohort, median age (IQR) was higher among DART patients than among RRT patients [8.5 years (0.9-14.6) versus 0.3 years (0.04-3.6); P < 0.001]. The odds of DART management were higher for children ages 1-2 years (aOR, 43.3; 95% CI: 2.73-684.3) and >5 years (aOR, 13.1; 95% CI: 1.85-93.4) than for those less than one-year-old. DART patients were more likely to have craniofacial abnormalities (aOR, 51.6; 95% CI: 2.50-1065.1), airway swelling (aOR, 240.1; 95% CI: 13.6-4237.2), or trauma (all DART managed). Among patients intubated by the DART, children with a history of difficult airway were more likely to have musculoskeletal (P = 0.04) and craniofacial abnormalities (P < 0.001), whereas children without a known history of difficult airway were more likely to have airway swelling (P = 0.04). Conclusion Specific clinical risk factors predict the need for emergency airway management by the DART in the pediatric hospital setting. The coordinated use of a DART to respond to difficult airway emergencies may limit attempts at endotracheal tube placement and mitigate morbidity.

Postoperative respiratory complications and disposition in patients with type 1 laryngeal clefts undergoing injection or repair - A single institution experience.

OBJECTIVE: Identify incidence and factors associated with respiratory complications after type 1 cleft repair. METHODS: Retrospective chart review of patients who underwent cleft repair over a 5-year period performed by a single surgeon. Primary endpoint was respiratory complications (oxygen desaturation <90%). Fisher's exact test was used to identify differences between repair types (endoscopic carbon dioxide laser-assisted repair and injection laryngoplasty). Logistic regression was used to identify predictors of respiratory events. RESULTS: Fifty-five patients were included. Thirty-four (62%) patients underwent endoscopic carbon dioxide laser-assisted repair and 21 (38%) underwent injection laryngoplasty. Average hospital stay for each group was 1.6 days (SD = 3.1) and 0.6 days (SD = 0.9), respectively. Desaturations occurred in three patients (9%) in the laser-assisted repair group and one patient (4%) in the injection group. All occurred within 3 h after surgery and resolved with supplemental oxygen, oral airway placement, and/or mask ventilation. Two affected patients had comorbid diagnosis of asthma (one had poor medication compliance), and one had a history of developmental delay and hypotonia. In the injection group, desaturations occurred in one patient with a history of tracheal stenosis and double aortic arch. No correlation existed between repair type and desaturation (p = 0.57). No variables were significant predictors of events. CONCLUSIONS: In this cohort, respiratory events after type 1 laryngeal cleft repair occurred early in the postoperative period, in children with cardiac and pulmonary comorbidities. This suggests postoperative admission may only be necessary for a select group of patients undergoing type 1 cleft repair. However, further research is needed to determine criteria for same-day discharge.

Cystic fibrosis transmembrane conductance regulator function, not TAS2R38 gene haplotypes, predict sinus surgery in children and young adults with cystic fibrosis.

BACKGROUND: Chronic rhinosinusitis symptomatology begins in early childhood individuals with cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to sinus development and disease. Genetic variants of the bitter taste receptor TAS2R38 have been suggested to contribute to sinus disease severity in individuals without CF. Our objective was to explore whether functional TAS2R38 haplotypes and CFTR function are associated with sinus disease or the need for sinus surgery in individuals with CF. METHODS: We conducted a retrospective study using prospectively collected data from the CF Twin-Sibling Study. The function of CFTR was assessed via chloride conductance. Genotyping of the TAS2R38 gene identified patients who were homozygous for the functional haplotype, heterozygous, or homozygous for nonfunctional haplotypes. Clustered multivariate logistic regression was performed, controlling for sex and family relationship. RESULTS: A total of 1291 patients were evaluated. Patients with ≤1% CFTR function were 1.56 times more likely to require sinus surgery than those with >1% CFTR function (p = 0.049). CFTR function did not correlate significantly with the presence of sinus disease (p = 0.30). In addition, there were no statistically significant differences in diagnosis of sinus disease or need for sinus surgery between patients with functional and nonfunctional TAS2R38 haplotypes. CONCLUSION: CFTR function correlates with need for sinus surgery, whereas TAS2R38 function does not appear to contribute to sinus disease or the need for sinus surgery in patients with CF.