Anesthetic considerations in children with asthma.

Due to the high prevalence of asthma and general airway reactivity, anesthesiologists frequently encounter children with asthma or asthma-like symptoms. This review focuses on the epidemiology, the underlying pathophysiology, and perioperative management of children with airway reactivity, including controlled and uncontrolled asthma. It spans from preoperative optimization to optimized intraoperative management, airway management, and ventilation strategies. There are three leading causes for bronchospasm (1) mechanical (eg, airway manipulation), (2) non-immunological anaphylaxis (anaphylactoid reaction), and (3) immunological anaphylaxis. Children with increased airway reactivity may benefit from a premedication with beta-2 agonists, non-invasive airway management, and deep removal of airway devices. While desflurane should be avoided in pediatric anesthesia due to an increased risk of bronchospasm, other volatile agents are potent bronchodilators. Propofol is superior in blunting airway reflexes and, therefore, well suited for anesthesia induction in children with increased airway reactivity.

Impact of climate variability on exercise-induced bronchospasm in adolescents living in a semi-arid region.

OBJECTIVE: To examine the impact of climate variability on the occurrence of exercise-induced bronchospasm in the rainy and dry seasons of a Brazilian semi-arid region. METHODS: This sample comprised 82 adolescents aged 15 to 18 years, who were submitted to exercise-induced bronchospasm assessment on a treadmill and outdoors, during the rainy and the dry season. Anthropometric variables, sexual maturity and forced expiratory volume in the first second were analyzed. Air temperature and humidity, decline in forced expiratory volume in the first second (%) and frequency of bronchospasm were compared between seasons using the independent Student's t test, the Wilcoxon and McNemar tests, respectively. The level of significance was set at p<0.05. RESULTS: The mean age was 15.65±0.82 years. Air temperature, air humidity and decline in forced expiratory volume in the first second (%) differed between seasons, with higher air temperature and humidity in the rainy season (29.6ºC±0.1 and 70.8%±0.6 versus 28.5ºC±0.2 and 48.5%±0.6; p<0.05). The decline in forced expiratory volume in the first second (%) was greater in the dry season (9.43%±9.97 versus 12.94%±15.65; p<0.05). The frequency of bronchospasm did not differ between seasons. CONCLUSION: The dry season had a negative impact on forced expiratory volume in the first second in adolescents, with greater decrease detected during this period. Findings of this study suggested bronchospasm tends to be more severe under low humidity conditions.

Paradoxical bronchospasm in U.S. military veterans with COPD or asthma at a tertiary VA medical center in Chicago, Illinois.

Inhaled short-acting ß2-adrenergic agonists can rarely elicit paradoxical bronchospasm (PB), which may be fatal. The purpose to this study was to determine whether post-bronchodilator PB is reported in spirometry test results of veterans with Chronic Obstructive Pulmonary Disease (COPD) or asthma followed at the Jesse Brown Veterans Affairs (VA) Medical Center in Chicago between 2017-2020. Eighteen of 1,150 test reports reviewed were identified with post-bronchodilator PB (1.5%).12 out of the 18 identified patients with PB had COPD, 4 hadasthma and 2 had asthma/COPD. No report alluded to post-bronchodilator PB. Among the identified PB patients, there were 17 males and one female, 14 African Americans, 3 Caucasian and one Latinx, aged 67±8 years (mean±SD) with BMI 28±5 kg/m2. Thirteen were ex-tobacco smokers, 4 current smokers and one never smoked. Most recent chest CT revealed emphysema in 8 veterans with COPD and bronchial wall thickening in 3. Chest radiographs of 4 veterans with asthma were unremarkable. All veterans were treated with inhaled ß2-adrenergic agonists. Five were treated with cardio selective beta1 blockers and 10 for gastroesophageal reflux disease. Eleven veterans were diagnosed with obstructive sleep apnea. In 12 veterans, inhaled albuterol (4 actuations)-induced decrease in FEV1 was 22±8% and 367±167 mL from baseline. In 6 veterans, only FVC decreased significantly from baseline (14±3% and 448±179 mL). No veteran reported respiratory symptoms during or after spirometry testing. Two veterans died during follow-up. Based on spirometry test reports, inhaled ß2-adrenergic agonists were discontinued in 2 veterans with COPD and asthma. We propose that post-bronchodilator PB observed during spirometry testing of veterans should be recognized and reported, and its possible clinical implications addressed accordingly.

Impact of climate variability on exercise-induced bronchospasm in adolescents living in a semi-arid region / Influência de alterações climáticas sobre a ocorrência do broncoespasmo induzido por exercício em adolescentes de uma região semiárida

ABSTRACT Objective: To examine the impact of climate variability on the occurrence of exercise-induced bronchospasm in the rainy and dry seasons of a Brazilian semi-arid region. Methods: This sample comprised 82 adolescents aged 15 to 18 years, who were submitted to exercise-induced bronchospasm assessment on a treadmill and outdoors, during the rainy and the dry season. Anthropometric variables, sexual maturity and forced expiratory volume in the first second were analyzed. Air temperature and humidity, decline in forced expiratory volume in the first second (%) and frequency of bronchospasm were compared between seasons using the independent Student's t test, the Wilcoxon and McNemar tests, respectively. The level of significance was set at p<0.05. Results: The mean age was 15.65±0.82 years. Air temperature, air humidity and decline in forced expiratory volume in the first second (%) differed between seasons, with higher air temperature and humidity in the rainy season (29.6ºC±0.1 and 70.8%±0.6 versus 28.5ºC±0.2 and 48.5%±0.6; p<0.05). The decline in forced expiratory volume in the first second (%) was greater in the dry season (9.43%±9.97 versus 12.94%±15.65; p<0.05). The frequency of bronchospasm did not differ between seasons. Conclusion: The dry season had a negative impact on forced expiratory volume in the first second in adolescents, with greater decrease detected during this period. Findings of this study suggested bronchospasm tends to be more severe under low humidity conditions.

RESUMO Objetivo: Verificar a influência das alterações climáticas sobre o broncoespasmo induzido por exercício, nos períodos chuvoso e seco de uma região do semiárido brasileiro. Métodos: Foram submetidos à avaliação do broncoespasmo em esteira ergométrica, em ambiente externo, nos períodos chuvoso e seco, 82 adolescentes, com idades de 15 a 18 anos. Foram avaliadas as variáveis antropométricas, a maturação sexual e o volume expiratório forçado no primeiro segundo. Para comparação da temperatura e umidade, queda do volume expiratório forçado no primeiro segundo (%) e frequência do broncoespasmo entre os períodos, foram utilizados o teste t de Student independente, o teste de Wilcoxon e o teste de McNemar, respectivamente. O nível de significância adotado foi p<0,05. Resultados: A média de idade foi 15,65±0,82 anos. A temperatura, a umidade e a queda do volume expiratório forçado no primeiro segundo (%) diferiram entre os períodos, com valores de temperatura e umidade maiores no período chuvoso (29,6ºC±0,1 e 70,8%±0,6 versus 28,5ºC±0,2 e 48,4%±0,6; p<0,05). A queda do volume expiratório forçado no primeiro segundo (%) foi maior no período seco (9,43%±9,97 versus 12,94%±15,65; p<0,05), e não foi encontrada diferença da frequência do broncoespasmo entre os períodos. Conclusão: O período seco influenciou negativamente no volume expiratório forçado no primeiro segundo de adolescentes, observando maior percentual de queda dessa variável nesse período. De acordo com os achados, propõe-se uma maior gravidade do broncoespasmo induzido por exercício em condições de baixa umidade.

Determining airway complications during anaesthesia induction: a prospective, observational, cross-sectional clinical study.

BACKGROUND: Although postoperative early airway complications are rarely observed, when they do develop, fatal results such as brain damage and cardiac arrest may occur. The Royal College of Anaesthetists and Difficult Airway Society investigated airway complications developing during anaesthesia over a period of 12 months within the context of the Fourth National Audit Project (NAP4) study. Inspired by that multicentre research project, this study aims to identify early airway complications that can develop in relation to anaesthesia induction in our hospital. METHODS: After our proposed study received approval from the Ethical Council, adult patients undergoing general anaesthesia at our operating theatres within the period of January-July 2018 were included in it. Demographic data, ventilation, American Society of Anesthesiologists (ASA) grade, Cormack-Lehane scores, tools that are used in airway management, and complications were recorded. RESULTS: Out of 909 patients in total, 752 were intubated; a laryngeal mask was placed on 157 of these patients. The complication rate was 5%, and the 3 most frequently observed complications were desaturation, bronchospasm and pharyngeal injuries. In the group having complications, the body mass index value, Cormack-Lehane, Mallampati, and ventilation scores were significantly higher than those with no complications. CONCLUSIONS: During routine general anaesthesia induction at our clinic, major or minor airway complications have developed with a frequency of 5%, and it was determined that desaturation was the most frequent reversible cause.

Obesity is a risk factor for exercise-induced bronchospasm in asthmatic adolescents.

INTRODUCTION: Exercise-induced bronchospasm (EIB) is common in young asthmatics and obesity is becoming an epidemic in this population. Both conditions can give rise to or worsen respiratory symptoms upon exercise and may interfere with recreational and sports activities. OBJECTIVE: To investigate the association between obesity and the risk and severity of EIB in asthmatic children and adolescents. METHODS: This study included data from asthmatic patients aged between 7 and 19 years undergoing treadmill running tests to evaluate EIB, defined as a reduction greater than or equal to 10% in forced expiratory volume in the first second (FEV1 ) compared to baseline. Eutrophic, obese, and overweight individuals were categorized according to body mass index z-score (eutrophic, -0.5 < z ≤ 1; overweight, 1 < z < 2; and obese, z ≥ 2). RESULTS: Of the 156 individuals studied (42% female), 58% were eutrophic, 22% overweight, and 19% obese. Seventy-three individuals (47%) presented with EIB, with higher risk among obese (OR, 2.86; 95% CI, 1.00-8.14; P = .05). Asthma severity was another independent risk factor for EIB (OR, 2.95; 95% CI, 1.36-6.42; P = .006). The number of patients in whom FEV1 returned to baseline values (difference less than 10% from baseline) at the 13th minute after challenge was lower in obese individuals compared to eutrophic and overweight ones (P = .04). Baseline FEV1 , gender, or age were not found to be risk factors for EIB in any of the groups. CONCLUSION: Obese youngsters with asthma present a greater risk for EIB with slower recovery than their nonobese peers. Clinicians should be aware of this association, especially in those with more severe disease, for adequate recognition and treatment.

Broncoespasmo y flushing tras la vacunación con neumococo polisacárida de 23 serotipos en pacientes crónicos / Bronchospasm and flushing after vaccination with 23 serotype pneumococcal polysaccharide in chronic patients

Objetivos: Describir las características clínico-epidemiológicas en una serie de casos de sospecha de reacciones adversas sistémicas registradas tras la administración de la vacuna frente a neumococo polisacárida de 23 serotipos (PNEUMOVAX23(R)). Calcular la incidencia acumulada de dicha reacción y conocer si se han descrito casos similares y/o compatibles en la literatura científica o en Farmacovigilancia. Métodos: Estudio observacional retrospectivo realizado entre 01/12/2015 y 30/09/2017 en la Unidad de Vacunas de un hospital autonómico de referencia. Se calculó la incidencia acumulada de la reacción adversa sistémica para esa vacuna. Se consultó la base de datos del Sistema Español de Farmacovigilancia (FEDRA). Resultados: Se registraron 9 sospechas de reacciones adversas sistémicas inmediatas (flushing + broncoespasmo + SatO2<95%). La incidencia acumulada fue 1,036%. El desenlace fue recuperado/resuelto para todos. No se encontraron casos similares y/o compatibles. Conclusiones: Las reacciones descritas no constan en la ficha técnica de PNEUMOVAX23(R). Epidemiológicamente no se puede establecer ninguna relación causal entre la aparición de los síntomas y las variables estudiadas. Esta información podría ser la base de investigaciones más amplias que supusieran la posible modificación de la ficha técnica

Objectives: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23(R)). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance. Methods: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted. Results: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found. Conclusions: The reactions described do not appear in the PNEUMOVAX23(R) data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet

[Bronchospasm and flushing after vaccination with 23 serotype pneumococcal polysaccharide in chronic patients]. / Broncoespasmo y flushing tras la vacunación con neumococo polisacárida de 23 serotipos en pacientes crónicos.

OBJECTIVE: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23®). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance. METHODS: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted. RESULTS: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found. CONCLUSIONS: The reactions described do not appear in the PNEUMOVAX23® data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet.

Incidence of severe critical events in paediatric anaesthesia in the United Kingdom: secondary analysis of the anaesthesia practice in children observational trial (APRICOT study).

The anaesthesia practice in children observational trial of 31,127 patients in 261 European hospitals revealed a high (5.2%) incidence of severe critical events in the peri-operative period and wide variability in practice. A sub-analysis of the UK data was undertaken to investigate differences compared with the non-UK cohort in the incidence and nature of peri-operative severe critical events and to attempt to identify areas for quality improvement. In the UK cohort of 7040 paediatric patients from 43 hospitals, the overall incidence of peri-operative severe critical events was lower than in the non-UK cohort (3.3%, 95%CI: 2.9-3.8 vs. 5.8%, 95%CI: 5.5-6.1, RR 0.57, p < 0.001). There was a lower rate of bronchospasm (RR 0.22, 95%CI: 0.14-0.33; p < 0.001), stridor (RR 0.42, 95%CI: 0.28-0.65; p < 0.001) and cardiovascular instability (RR 0.69, 95%CI: 0.55-0.86; p = 0.001) than in the non-UK cohort. The proportion of sicker patients where less experienced teams were managing care was lower in the UK than in the non-UK cohort (10.4% vs. 20.4% of the ASA physical status 3 and 9% vs. 12.9% of the ASA physical status 4 patients). Differences in work-load between centres did not affect the incidence and outcomes of severe critical events when stratified for age and ASA physical status. The lower incidence of cardiovascular and respiratory complications could be partly attributed to more experienced dedicated paediatric anaesthesia providers managing the higher risk patients in the UK. Areas for quality improvement include: standardisation of serious critical event definitions; increased reporting; development of evidence-based protocols for management of serious critical events; development and rational use of paediatric peri-operative risk assessment scores; implementation of current best practice in provision of competent paediatric anaesthesia services in Europe; development of specific training in the management of severe peri-operative critical events; and implementation of systems for ensuring maintenance of skills.

[Diving and asthma: Literature review]. / Plongée sous-marine et asthme : revue de littérature.

INTRODUCTION: Scuba diving has long been contraindicated for asthmatics. Recommendations are evolving towards authorisation under certain conditions. Our objective was to review the literature on the risks associated with scuba diving among asthmatics and about recommendations on this subject. MATERIALS AND METHODS: We used the MEDLINE and LiSSa databases, until June 2018, in French, English or Spanish language, with the keywords "asthma AND diving" and "asthme plongée" respectively. References to the first degree were analyzed. RESULTS: We have included 65 articles. Risk of bronchospasm is well documented, particularly in cold and/or deep water, or in the event of exposure to allergens (compressor without filter). Nonasthmatic atopic divers may be at greater risk of developing bronchial hyper-reactivity. Although the theoretical risk exists, epidemiological studies do not seem to show an over-risk of barotrauma, decompression sickness or arterial gas embolism in asthmatics. French, British, American, Spanish and Australian societies agreed on the exclusion of patients with moderate to severe persistent asthma, FEV1<80%, active asthma in the last 48hours, exercise/cold asthma and poor physical fitness. CONCLUSION: A diver's examination should include a triple assessment: asthma control, number of exacerbations and treatment compliance. Homogenizing the recommendations would improve the framework for the practice of diving among asthmatics and allow larger studies in this population. Communicating the current recommendations remains important to divers, dive instructors and doctors in the context of the development of scuba diving.

[Occurrence of delayed symptoms after a challenge test with methacholine]. / Survenue de symptômes tardifs après un test de provocation par la méthacholine.

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

Impact of upper respiratory tract infections on perioperative outcomes of children undergoing therapeutic cardiac catheterisation.

BACKGROUND: Recent upper respiratory tract infection (URI) is associated with increased incidence of perioperative complications in children undergoing open heart surgery. As a result, surgery is often postponed. However, the effect of recent URI on the incidence of perioperative complications in children undergoing therapeutic cardiac catheterisation is unknown. We investigated the perioperative outcomes of congenital heart disease (CHD) children with recent URI who underwent elective therapeutic catheterisation. METHODS: We prospectively included children treated for CHD. Before surgery, parents or legal guardians were interviewed to complete a questionnaire on the child's demographics, history of asthma and passive smoking, and URI symptoms. Recorded perioperative respiratory adverse events (PRAEs) included laryngospasm, bronchospasm, breath holding, oxygen desaturation, and severe cough. Information on postoperative dysphoria, fever, copious sputum, and vomiting was obtained by telephone 24 h after surgery. RESULTS: Of 363 included children, 169 had recently (within 2 weeks) had a URI. The URI did not affect the incidence of laryngospasm, bronchospasm, breath holding, fever, or vomiting. The incidence of desaturation, severe cough, dysphoria, and copious sputum were significantly increased. Independent risk factors for PRAEs in children with a recent URI included age, passive smoking, and presence of rhinorrhoea or moist cough. The lengths of stay in the hospital and intensive care unit were not significantly different between groups. CONCLUSION: Although recent URI increased the incidence of PRAEs in children undergoing therapeutic cardiac catheterisation, most CHD patients with recent URI can undergo elective therapeutic cardiac catheterisation without serious adverse events or prolonged hospitalisation.

Safety of pulmonary function testing: data from 20 years.

BACKGROUND: Pulmonary function testing (PFT) is a key investigation in the evaluation of individuals with respiratory symptoms; however, the safety of routine and specialised PFT testing has not been reported in a large data set. Using patient safety incident (PSI) records, we aimed to assess risk of PFT and to characterise these events and any associated risk factors. METHODS: In this single-centre audit, demographics and PSI data were collected and categorised for PFT performed between 1996 and 2016 and subdivided into cardiopulmonary or non-cardiopulmonary events. The severity of each PSI was rated using the NHS National Patient Safety Agency and any hospital admission reported. RESULTS: There were 119 PSIs reported from 186 000 PFT; that is, 0.6 PSIs per 1000 tests. Cardiopulmonary PSIs were 3.3 times more likely to occur than non-cardiopulmonary (95% CI 2.17 to 5.12). Syncope was the most frequently occurring cardiopulmonary PSI. Cardiopulmonary exercise testing was associated with 2 PSIs per 1000 tests. PSIs necessitating hospital admission and/or emergency department attendance occurred approximately once every 10 000 tests and there was no PFT-associated mortality. CONCLUSION: Routine and specialised PFT is safe for patients, in the context of established screening preparticipation guidelines. In the event of a PSI, these are likely to be low risk of harm. Our findings highlight the most common PSIs encountered during PFT to facilitate risk reduction.

Rainfall-Associated Bronchospasm Epidemics: The Epidemiological Effects of Air Pollutants and Weather Variables.

BACKGROUND: This study compares different risk factors in patients visiting a hospital during five rainfall-associated bronchospasm epidemics in Ahvaz and those visiting on other occasions. METHODS: This case-control study was conducted on 5307 patients with bronchospasm admitted to the Emergency Department of Imam Khomeini Hospital in Ahvaz (Iran) from late October to December (as the epidemic) and 916 patients admitted from late January to March (as the nonepidemic) in 2011 to 2015. RESULTS: A total of the 41.7% of the cases and 48.8% of the controls had episodes of bronchospasm, suggesting a significant difference between the two groups (P < 0.001). The mean concentrations of PM10, NO, NO2, and NO x pollutants (except O3) were significantly higher in the nonepidemic periods (P < 0.05). The adjusted analysis showed a direct significant relationship between emergency respiratory admissions and each unit of increase in NO and SO2 concentration during the epidemic periods and NO2 concentration during the nonepidemic periods. During the epidemic periods, a direct and significant relationship was also observed between respiratory admissions and each unit of increase in relative humidity and evaporation. CONCLUSION: The results suggest that certain pollutants and weather variables are associated with the risk of emergency respiratory admissions during epidemic periods.

Exercise-induced bronchospasm in a hot and dry region: study of asthmatic, rhinitistic and asymptomatic adolescents.

BACKGROUND: Exercise-induced bronchospasm (EIB) is the bronchial narrowing that occurs after intense exercise in a significant number of asthmatics and in some non-asthmatics. This study aims to evaluate the occurrence of EIB in adolescents with asthma, rhinitis and respiratory asymptomatics in a hot and dry climate. RESEARCH DESIGN AND METHODS: This is a cross-sectional study based on an epidemiological study that evaluated the prevalence of asthma in schoolchildren in a semi-arid zone of Brazil. The EIB was defined as a reduction in forced expiratory volume in first second (FEV1) greater than 10%. RESULTS: A total of 114 individuals participated in the study (36.8% male), of whom 54 were asymptomatic, 30 asthmatic and 30 with rhinitis. Asthmatics presented a higher proportion of EIB in comparison to rhinitis and asymptomatics (46.7% vs. 13.3% and 7.4%, p = 0.001) and none of the individuals had severe EIB (ΔFEV1 ≥ 50%). CONCLUSIONS: A large proportion of the asthmatics selected from the community for the clinical study had EIB. Among participants with rhinitis, EIB was found in slightly more than 10%, while in the asymptomatics the frequency was slightly more than 5%. This study presents an important aspect in individuals living in hot and dry climates.

An update on the perioperative management of children with upper respiratory tract infections.

PURPOSE OF REVIEW: This review summarizes the current evidence for the management of children with recent upper respiratory tract infections (URTIs). Furthermore, the review includes management guidelines for children with URTIs. RECENT FINDINGS: Good history and clinical examination is sufficient in most children presenting with URTI. Testing for immune markers or preoperative nitric oxide measurement does not add any additional value. Preoperative bronchodilator administration, intravenous induction with propofol, and noninvasive airway management all reduce the occurrence of respiratory adverse events. SUMMARY: Most children can be safely anaesthetized even in the presence of an URTIs if the perioperative anaesthesia management is optimized. In this review article, we have included a management algorithm for children with URTI presenting for elective surgery.

A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm.

Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [3H]-NBTI binding affinity (Ki) and [3H]-adenosine uptake (IC50) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥13.3x Ki, ≥4x IC50) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥0.1x Ki, ≥0.05x IC50) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds Ki<1µM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP >5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders.