Aerosolized drug delivery in awake and anesthetized children to treat bronchospasm.

Bronchospasm is a common respiratory adverse event in pediatric anesthesia. First-line treatment commonly includes inhaled salbutamol. This review focuses on the current best practice to deliver aerosolized medications to awake as well as anesthetized pediatric patients and discusses the advantages and disadvantages of various administration techniques. Additionally, we detail the differences between various airway devices used in anesthesia. We highlight the unmet need for innovation of orally inhaled drug products to deliver aerosolized medications during pediatric respiratory critical events such as bronchospasm. It is therefore important that clinicians remain up to date with the best clinical practice for aerosolized drug delivery in order to prevent and efficiently treat pediatric patients experiencing life-threatening respiratory emergencies.

The ß2-adrenergic receptor-ROS signaling axis: An overlooked component of ß2AR function?

ß2-Adrenergic receptor (ß2AR) agonists are clinically used to elicit rapid bronchodilation for the treatment of bronchospasms in pulmonary diseases such as asthma and COPD, both of which exhibit characteristically high levels of reactive oxygen species (ROS); likely secondary to over-expression of ROS generating enzymes and chronically heightened inflammation. Interestingly, ß2AR has long-been linked to ROS, yet the involvement of ROS in ß2AR function has not been as vigorously studied as other aspects of ß2AR signaling. Herein, we discuss the existing body of evidence linking ß2AR activation to intracellular ROS generation and importantly, the role of ROS in regulating ß2AR function. The reciprocal interplay of the ß2AR and ROS appear to endow this receptor with the ability to self-regulate signaling efficacy and ligand binding, hereby unveiling a redox-axis that may be unfavorably altered in pathological states contributing to both disease progression and therapeutic drug responses.

Three-trocar laparoscopic cholecystectomy under spinal anesthesia in a patient with asthma.

INTRODUCTION: Laparoscopy is perceived as the state-of-the-art technique for a wide variety of operations but is contraindicated by comorbidities such as respiratory diseases. We present the case of a patient affected by asthma who underwent a successful three-trocar low-pressure pneumoperitoneum under spinal anesthesia. CASE REPORT: A 58 year-old male with symptomatic gallstones had partly-controlled asthma and respiratory allergies. Potential bronchospasm was avoided by a less invasive laparoscopic technique. Under spinal anesthesia open pneumoperitoneum was achieved at the umbilicus. Two more trocars were inserted. A cholecystectomy was performed in 90 minutes keeping the patient in a supine position and the pneumopneumoperitoneum at 8 mmHg. The post-operative course was uneventful. Discharge to home occurred on day two. DISCUSSION: Laparoscopy is contraindicated in the presence of hemodynamic instability and inability of the patient to tolerate laparoscopic surgery. Asthma is caused by bronchoconstriction from a myriad possible stimuli requiring a specific anesthetic plan. Spinal anesthesia under low pressure pneumoperitoneum is a safe alternative to general anesthesia in high risk candidates. In experienced hand, a three-trocar cholecystectomy is safe and feasible. CONCLUSION: Our patient represented a challenging case due to a partly-controlled asthma. Bronchospasm under general anesthesia was prevented by spinal anesthesia to keep a spontaneous physiologic respiration, irrigation of the right subdiaphragmatic surface with lidocaine to control right shoulder pain, safe dissection by three trocars, a pneumoperitoneum at 8 mmHg, the supine position to prevent significant physiologic changes and minimize diaphragmatic irritation.

Omalizumab can inhibit respiratory reaction during aspirin desensitization.

BACKGROUND: Aspirin desensitization has been associated with benefit in management of aspirin-exacerbated respiratory disease (AERD). An intervention that would encourage aspirin desensitization to be performed more frequently has substantial potential for improving outcomes and quality of life in patients with AERD. OBJECTIVE: We investigated whether omalizumab administration would be associated with attenuation of aspirin-provoked bronchospasm in patients with AERD undergoing aspirin desensitization. METHODS: We carried out a randomized, double-blind, placebo-controlled study in which subjects with AERD who fulfilled label criteria for omalizumab received omalizumab or placebo for 16 weeks, and then underwent aspirin desensitization. RESULTS: Eleven subjects completed aspirin desensitization. Of the 7 who were randomized to omalizumab, 5 had no respiratory reaction during aspirin desensitization. Compared with placebo, omalizumab was associated with a significantly greater likelihood for subjects with AERD to have no respiratory reaction during desensitization (P = .04, Fisher exact test). There was an overall difference in urinary leukotriene E4 (LTE4) levels in subjects who received omalizumab and did not have a respiratory reaction during desensitization compared with subjects randomized to placebo (P = .035, mixed model with interaction). Urinary LTE4 levels were significantly higher with respiratory reaction in placebo subjects compared with levels obtained after the 100-mg dose in AERD subjects who had no respiratory reaction (P < .001, mixed model with interaction). CONCLUSION: In atopic AERD subjects, omalizumab administration for 16 weeks was associated with "clinically silent" desensitization. Further studies to investigate the therapeutic utility of omalizumab in patients with AERD who are candidates for aspirin desensitization are warranted based on these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00555971.

Experience of correcting endothelial dysfunction in children-residents of radioactively contaminated areas by nitric oxide potential donator citrulline. / DOSVID KOREKTsIÏ ENDOTELIAL'NOÏ DYSFUNKTsIÏ U DITEY̆, MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆, ZA DOPOMOGOIu POTENTsIY̆NOGO DONATORA OKSYDU AZOTU ­ TsYTRULINU.

OBJECTIVE: to determine the effectiveness of citrulline use for correcting endothelial dysfunction in children resi dents of radioactively contaminated areas. MATERIALS AND METHODS: A group of children residents of radioactively contaminated areas with the presence of clinical and paraclinical signs of endothelial dysfunction was selected to assess the effectiveness of correcting endothelial dysfunction by the usage of NO potential donator - citrulline according to the data of selective screen ing. There were determined the biochemical parameters of the content of NO stable metabolites, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumen tal indices of vascular endothelium dependent reaction on occlusion test, the lung ventilation capacity, the bioelec tric activity of the myocardium, the autonomic regulation of the cardiovascular system.Examined children were received a course of citrulline malate. RESULTS AND CONCLUSIONS: An increased content of serum L arginine, nitrite, and amounts of NO metabolites was established in children with endothelial dysfunction who were received a course of citrulline malate. Bronchospasm elimination was noted in the significant part of examined patients after the drug use. Decreased recovery period and increased period of hypercompensation for thermographic circulation index in the test with post occlusion reac tive hyperemia were detected by an evaluation of indicators for vascular endothelium dependent vasodilatation using thermographic method indicating an increased endothelial vasomotor capacity. There was tendency to improve the processes of autonomic regulation of the heart rhythm and repolarization of the heart muscle. The antioxidant effect of used citrulline malate course was determined as: decreased content of serum LPO end products that react with thiobarbituric acid under elevated activity of antioxidant - catalase. An increase in the percentage of T lymphocyte, normalization of their subpopulation composition was noted in dynamics of citrulline malate application.

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.

Airway Hyperresponsiveness in Asthma: Measurement and Clinical Relevance.

Airway hyperresponsiveness is a characteristic feature of asthma, and its measurement is an important tool in its diagnosis. With a few caveats, methacholine bronchial provocation by a 2-minute tidal breathing method is highly sensitive; a negative test result (PC20 > 16 mg/mL, PD20 > 400 µg) rules out current asthma with reasonable certainty. A PC20 value of less than 1 mg/mL/PD20 value of less than 25 µg is highly specific (ie, diagnostic) but quite insensitive for asthma. For accurate interpretation of the test results, it is important to control and standardize technical factors that have an impact on nebulizer performance. In addition to its utility to relate symptoms such as cough, wheeze, and shortness of breath to variable airflow obstruction (ie, to diagnose current asthma), the test is useful to make a number of other clinical assessments. These include (1) evaluation of patients with occupational asthma, (2) evaluation of patients with exercise-induced respiratory symptoms, (3) evaluation of novel asthma medications, (4) evaluation of relative potency of inhaled bronchodilators, (5) as a biomarker to adjust anti-inflammatory therapy to improve clinical outcomes, and (6) in the evaluation of patients with severe asthma to rule out masqueraders such as laryngeal dysfunction. The actual mechanism of altered smooth muscle behavior in asthma that is assessed by direct (eg, methacholine) or indirect (eg, allergen) bronchial provocation remains one of the most fundamental questions related to asthma that needs to be determined. The test is underutilized in clinical practice.

Case Report of S1Q3T3 Electrocardiographic Abnormality in a Pregnant Asthmatic Patient During Acute Bronchospasm.

BACKGROUND Asthma is the most common chronic pulmonary disease during pregnancy. Several previous reports have documented reversible electrocardiographic changes during severe acute asthma attacks, including tachycardia, P pulmonale, right bundle branch block, right axis deviation, and ST segment and T wave abnormalities. CASE REPORT We present the case of a pregnant patient with asthma exacerbation in which acute bronchospasm caused S1Q3T3 abnormality on an electrocardiogram (ECG). The complete workup of ECG findings of S1Q3T3 was negative and correlated with bronchospasm. The S1Q3T3 electrocardiographic abnormality can be seen in acute bronchospasm in pregnant women. The other causes like pulmonary embolism, pneumothorax, acute lung disease, cor pulmonale, and left posterior fascicular block were excluded. CONCLUSIONS Asthma exacerbations are of considerable concern during pregnancy due to their adverse effect on the fetus, and optimization of asthma treatment during pregnancy is vital for achieving good outcomes. Prompt recognition of electrocardiographic abnormality and early treatment can prevent adverse perinatal outcomes.

[THE INFLUENCE OF THE NORMOBARIC HYPOXIA FOR THE BREATHIHG INDEXES OF THE CHILDREN LIVED IN RADIOACTIVE CONTAMINATED TERRITORIES].

There was conducted a research of the influence the sanogenic level of intermittent normobaric hypoxia (INH) for children lived in radioactively contaminated territories. The research involved 106 children in the age from 6 to 17 with symptoms ofbronchospasm: 55 persons of the main group and 51 persons of the screening group. It was confirmed that after the course of sessions INH (12 % oxygen in nitrogen) the respiratory system has changed. It is known statistically that in the main group the indexes of ventilation lung capacity have increased : vital capacity of the lungs, bronchial obstruction proximal bronchi of large and medium diameter, and distal bronchi small diameter. The bronchospasm has removed completely or partially. It was confirmed significantly that the breath-holding time becomes longer (test Stange) and heart rat reduced in companson with the screening group.

Anaphylaxis-induced hyperfibrinolysis in pregnancy.

Anaphylaxis during pregnancy is rare but life threatening to both mother and fetus. The anaesthetist may be unexpectedly faced with an obstructing airway, severe bronchospasm and cardiac arrest requiring perimortem caesarean delivery to relieve aortocaval compression. We present a case of anaphylaxis-induced hyperfibrinolysis, an infrequently discussed complication that could exacerbate postpartum haemorrhage and hamper resuscitative efforts.

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm.

Changes in the androgen levels in asthmatic men may be associated with the severity of asthma. Androgens induce a nongenomic relaxation in airway smooth muscle, but the underlying mechanisms remain unclear. The aim of this study was to investigate the potential bronchorelaxing action of testosterone (TES) and its metabolites (5α- and 5ß-dihydrotestosterone (DHT). A preventive effect on ovalbumin (OVA)-induced bronchospasm was observed in sensitized guinea pigs for each androgen. Androgens were studied in response to bronchoconstrictors: carbachol (CCh) and KCl in isolated trachea rings with and without epithelium from non-sensitized and sensitized animals as well as on OVA-induced contraction. Androgens concentration-dependently abolished the contraction in response to CCh, KCl, and OVA. There were significant differences in the sensitivity to the relaxation induced by each androgen. 5ß-DHT was more potent for relaxing KCl-induced contraction, while TES and 5α-DHT were more potent for CCh- and OVA-induced contraction. No differences were found in preparations with and without epithelium or in the presence of a nitric oxide (NO) synthase inhibitor or an inhibitor of K(+) channels. These data indicate the absence of involvement of the epithelium-, NO- and K(+) channels-dependent pathway in androgen-induced relaxation. However, in dissociated tracheal myocytes loaded with the calcium-binding fluorescent dye Fura -2, physiological concentrations of androgens decreased the KCl-induced [Ca(2+)]i increment. 5ß-DHT was the most potent at decreasing KCl-induced [Ca(2+)]i increment and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca(2+) influx through L-type Ca(2+)channels but additional Ca(2+) entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action.

[Effects of penehyclidine inhalation on postoperative pulmonary complications of elderly patients after long-duration surgery].

OBJECTIVE: To explore the effects of penehyclidine inhalation on the incidence of pulmonary complications in elderly patients after long-duration surgery. METHODS: For this prospective, double-blind and randomized controlled trial, 90 elderly patients undergoing long-duration surgery ( ≥ 3 hours) under general anesthesia and transferred into intensive care unit (ICU) of Peking University First Hospital during February 14, 2012 to September 13, 2012 were enrolled. After extubation, they were randomized into 3 groups to receive an inhalation of penehyclidine hydrochloride, ipratropium bromide or normal saline for 3 consecutive days. The primary endpoint was the incidence of pulmonary complications within 6 days post-extubation. RESULTS: The incidence of bronchospasm was 3.3%, 3.2% and 20.7% respectively. And the rate of aminophylline use was 0,0 and 10.3% respectively (P = 0.025 and P = 0.038); the airway tract spasm-free duration within 6 days after extubation was 5.8 (5.5-6.2), 5.8 (5.5-6.2) and 5.3 (4.8-5.9) days (P = 0.028); the overall incidence of pulmonary complications was 70.0%, 71.0% and 75.9% (P = 0.865). CONCLUSIONS: For elderly patients after long-duration surgery, a prophylactic atomizing inhalation of penehyclidine decreases the incidence of bronchospasm and the rate of aminophylline use after extubation.However, the overall incidence of pulmonary complications has no change.

Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model.

Primates secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA); in humans, its levels are low during childhood and start declining after the fourth decade. It has been postulated that the progressive decline in DHEA levels may be related with the severity of asthma associated with age. To determine whether DHEA may regulate the airway smooth muscle (ASM) activity, isolated tracheal rings with and without epithelium from male guinea pigs were isometrically recorded to characterize the response of ASM to DHEA at different concentrations on KCl- and carbachol (CCh)-induced contraction as well as on ovalbumin (OVA)-induced contraction in sensitized guinea pigs. Additionally, we used barometric plethysmography in sensitized guinea pigs in order to compare changes of the lung resistance increased by the antigen challenge to OVA in the absence and presence of different doses of DHEA. DHEA concentration-dependently abolished the contraction to KCl, CCh and OVA, and no differences were found in preparations with and without epithelium. DHEA-induced relaxation was not modified by the suppression of protein synthesis or transcription, pharmacological inhibition of nitric oxide (NO) synthase, nor by antagonist of ß2-adrenergic receptors or an inhibitor of the 3ß-HSD enzyme. Likewise, Ca(2+)-induced contraction in Ca(2+)-free depolarized tissues was antagonized by DHEA, and the contraction to the L-type voltage-dependent calcium channel activator (Bay K 8644) was inhibited by DHEA. Furthermore, DHEA prevented OVA-induced increases in lung resistance. These results indicate that DHEA-induced relaxation in ASM is a nongenomic (membrane) action and is not produced after its bioconversion. The data suggest that DHEA-induced relaxation is an epithelium- and NO-independent mechanism that involves a blockade of voltage-dependent calcium channels and possible non-selective cation channels.

Design and synthesis of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents.

A series of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones were synthesized by the reaction of 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one with various amines. The starting material, 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one was synthesized from 2-methyl aniline. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. Compound 2-(3-(4-methylpiperazin-1-yl) propylthio)-3-(2-methyl phenyl) quinazolin-4(3H)-one (OT5) emerged as the most active compound (71.70% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound OT5 shows negligible sedation (7%) compared to chlorpheniramine maleate (33%). Therefore, compound OT5 can serve as the leading molecule for further development into a new class of H(1)-antihistaminic agents.

Design and synthesis of novel 3-(4-chlorophenyl)-2-(3-substituted propyl thio) quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents.

A series of novel 3-(4-chlorophenyl)-2-(3-substituted propyl) quinazolin-4-(3H)-ones have been synthesized and tested for their in vivo H1-antihistaminic activity on conscious guinea pigs. All the test compounds have protected the animals from histamine induced bronchospasm significantly. Compound 3-(4-chlorophenyl)-2-(3-(4-methylpiperazin-1-yl) propylthio) quinazolin-4(3H)-one (PC5) emerged as the most active compound (77.53% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound PC5 shows negligible sedation (6.16%) compared to chlorpheniramine maleate (29.58%). Therefore, compound PC5 can serve as the lead molecule for further development into a new class of H1-antihistaminic agents.