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1.
Mol Biol Rep ; 51(1): 202, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38270668

ABSTRACT

BACKGROUND: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. METHODS AND RESULTS: Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-ß and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW. CONCLUSIONS: Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.


Subject(s)
Achyranthes , Anaphylaxis , Anti-Allergic Agents , Asthma , Bronchial Spasm , Animals , Mice , Ovalbumin , Histamine , p-Methoxy-N-methylphenethylamine , Disease Models, Animal , Interleukin-5 , Asthma/chemically induced , Asthma/drug therapy , Cytokines
2.
Prehosp Emerg Care ; 28(2): 231-242, 2024.
Article in English | MEDLINE | ID: mdl-37276151

ABSTRACT

Background/Objective: Bronchospasm, caused by asthma and other related conditions, is a significant cause of morbidity and mortality commonly managed by emergency medical services (EMS). We aimed to evaluate the quality of prehospital management of bronchospasm by EMS in the US.Methods: The National EMS Information System Public Release Research dataset, a nationwide convenience sample of prehospital patient care report data from 2018 to 2019, was used to capture 9-1-1 activations where patients aged ≥2 years were treated and transported by EMS for suspected bronchospasm. First, we described the extent to which EMS care met eight quality measures identified from available statewide EMS protocols, existing quality measures, and national guidelines. Second, we quantified the extent of risk-standardized agency-level variation in administration of inhaled beta agonists and systemic corticosteroids using logistic regression models, accounting for patient characteristics, severity, and clustering by agencies. Third, we compared rates of completed prehospital interventions between pediatric (age <18 years) versus adult patients using two-sample t-tests.Results: A total of 1,336,988 EMS encounters for suspected bronchospasm met inclusion criteria. Median age of patients was 66 years, with only 4% pediatric; 55% were female. Advanced life support (ALS) units managed 94% of suspected bronchospasm. Respiratory rate (98%) and pulse oximetry (96%) were documented in nearly all cases. Supplemental oxygen was administered to hypoxic patients by 65% of basic life support (BLS) and 73% of ALS units. BLS administered inhaled beta-agonist therapy less than half the time (48%), compared to 77% by ALS. ALS administered inhaled anticholinergic therapy in 38% of cases, and systemic corticosteroids in 19% of cases. Pediatric patients were significantly less likely to receive supplemental oxygen when hypoxic, inhaled beta-agonists, inhaled anticholinergics, or systemic corticosteroids.Conclusions: We found important gaps in recent EMS practice for prehospital care of suspected bronchospasm. We highlight three targets for improvement: inhaled beta-agonist administration by BLS, systemic corticosteroid administration by ALS, and increased interventions for pediatric patients. These findings indicate important areas for research, protocol modification, and quality improvement efforts to improve EMS management of bronchospasm.


Subject(s)
Bronchial Spasm , Emergency Medical Services , Adult , Aged , Child , Female , Humans , Male , Adrenal Cortex Hormones , Bronchial Spasm/drug therapy , Cross-Sectional Studies , Oxygen , United States , Child, Preschool , Adolescent , Middle Aged
3.
Anaesthesia ; 79(5): 498-505, 2024 May.
Article in English | MEDLINE | ID: mdl-38205586

ABSTRACT

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest. Among 59 cases reported as possible anaphylaxis, 33 (56%) were judged to be so by the review panel with high or moderate confidence. Causes in excluded cases included: isolated severe hypotension; bronchospasm; and oesophageal intubation. Severe bronchospasm leading to cardiac arrest was uncommon, but notably in one case led to a reported flat capnograph. In the baseline survey, anaesthetists estimated anaphylaxis as the cause of 10% of cases of peri-operative cardiac arrests and to be among the four most common causes. In a year-long registry of peri-operative cardiac arrest, suspected anaphylaxis was the seventh most common cause accounting for 4% of reports. Initial management was most often with low-dose intravenous adrenaline, and this was without complications. Both the NAP7 baseline survey and case registry provided evidence of reluctance to starting chest compressions when systolic blood pressure had fallen to below 50 mmHg and occasionally even when it was unrecordable. All 33 patients were resuscitated successfully but one patient later died. The one death occurred in a relatively young patient in whom chest compressions were delayed. Overall, peri-operative anaphylaxis leading to cardiac arrest occurred with a similar frequency and patterns of presentation, location, initial rhythm and suspected triggers in NAP7 as in the 6th National Audit Project (NAP6). Outcomes in NAP7 were generally better than for equivalent cases in NAP6.


Subject(s)
Anaphylaxis , Bronchial Spasm , Heart Arrest , Humans , Anaphylaxis/epidemiology , Anaphylaxis/etiology , Anaphylaxis/therapy , Epinephrine , Heart Arrest/etiology , Heart Arrest/therapy , Anesthetists
4.
Am J Emerg Med ; 68: 213.e5-213.e9, 2023 06.
Article in English | MEDLINE | ID: mdl-37120400

ABSTRACT

Bronchospasm is caused by reversible constriction of the smooth muscles of the bronchial tree. This causes obstruction of the lower airways, which is commonly seen at the emergency department (ED) in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. Ventilation may be difficult in mechanically intubated patients with severe bronchospasm due to airflow limitation, air trapping, and high airway resistance. The beneficial effects of volatile inhaled anesthetic gas had been reported due to its bronchodilation properties. In this case series, we would like to share our experience delivering inhaled volatile anesthetic gas via a conserving device for three patients with refractory bronchospasm at the ED. Inhaled anesthetic gas is safe, feasible and should be considered as an alternative rescue therapy for ventilated patients with severe lower airway obstruction.


Subject(s)
Anesthetics, Inhalation , Asthma , Bronchial Spasm , Humans , Bronchial Spasm/chemically induced , Asthma/complications , Asthma/therapy , Lung , Emergency Service, Hospital
5.
Anesthesiology ; 136(4): 551-566, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35226725

ABSTRACT

BACKGROUND: Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. METHODS: This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. RESULTS: A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. CONCLUSIONS: In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications.


Subject(s)
Bronchial Spasm , Pulmonary Atelectasis , Bronchial Spasm/chemically induced , Bronchial Spasm/complications , Double-Blind Method , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Pulmonary Atelectasis/complications , Quinuclidines/adverse effects , Quinuclidines/therapeutic use
6.
Anesth Analg ; 134(5): 1043-1053, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35020636

ABSTRACT

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.


Subject(s)
Neostigmine , Neuromuscular Blockade , Sugammadex , Anaphylaxis/chemically induced , Bradycardia/chemically induced , Bradycardia/diagnosis , Bradycardia/epidemiology , Bronchial Spasm/chemically induced , Child , Cohort Studies , Delayed Emergence from Anesthesia/chemically induced , Heart Arrest/etiology , Humans , Neostigmine/adverse effects , Neuromuscular Blockade/adverse effects , Retrospective Studies , Sugammadex/adverse effects
7.
Paediatr Anaesth ; 32(2): 156-166, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34862993

ABSTRACT

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.


Subject(s)
Bronchial Spasm , Administration, Inhalation , Aerosols , Albuterol/therapeutic use , Bronchial Spasm/drug therapy , Bronchial Spasm/prevention & control , Child , Humans , Nebulizers and Vaporizers , Wakefulness
8.
Paediatr Anaesth ; 32(2): 148-155, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34890494

ABSTRACT

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.


Subject(s)
Anesthetics , Asthma , Bronchial Spasm , Airway Management , Anesthesia, General/adverse effects , Anesthetics/adverse effects , Asthma/complications , Asthma/therapy , Bronchial Spasm/epidemiology , Bronchial Spasm/etiology , Child , Humans
9.
J Pak Med Assoc ; 72(11): 2160-2165, 2022 Nov.
Article in English | MEDLINE | ID: mdl-37013278

ABSTRACT

Objectives: To observe the effect of a single dose of tramadol 1mg/kg on haemodynamic changes related to extubation, and to assess the quality of emergence as judged by incidence of cough, laryngospasm and bronchospasm. METHODS: The double-blind randomised controlled trial was conducted at the Department of Anaesthesiology, Aga Khan University Hospital, Karachi, from 2016 to 2017, and comprised patients of either gender aged 18-65 years scheduled for elective supratentorial craniotomy under general anaesthesia. The patients were randomised to two Tramadol and Saline groups. The drug was given 45 minutes before extubation at the time of dura closure. The patients were extubated after resumption of adequate spontaneous breathing. Invasive blood pressure and heart rate were recorded one minute before reversal, at 1 minute interval for five minutes and then every 10 minute for 30 minutes after extubation. Cough, laryngospasm and bronchospasm were noted. Pain, post-operative nausea, vomiting, convulsions and conscious levels were also noted till 6 hours post-operatively. Data was analysed using SPSS 19. RESULTS: Of the 80 patients enrolled, 79(98.75%) completed the study. Of them, 38(48%) were in the Tramadol group; 27(71.1%) males and 11(28.9%) females with a mean age of 43.42±13.2 years. The remaining 41(52%) patients were in the Saline group; 28(68.3%) males and 13(31.7%) females with a mean age of 45.9±15.9 years. Intergroup comparison showed no significant difference in the extubation response (p>0.05), but the changes in blood pressure and heart rate were shorter in magnitude and duration in the Tramadol group compared to the baseline. Significant rise in blood pressure and heart rate were observed in the Saline group at 5 minutes after extubation (p=0.046). There was no difference in the quality of emergence as judged by cough or secondary complications (p>0.05). CONCLUSIONS: Tramadol 1mg/kg was considered superior in attenuating the duration and magnitude of haemodynamic response in the shape of hypertension and tachycardia during extubation, but did not affect other parameters in patients undergoing craniotomy. Clinical Trial Number: Clinical Trials.gov PRS: NCT02964416, https://clinicaltrials.gov/ct2/show/NCT02964416.


Subject(s)
Bronchial Spasm , Laryngismus , Tramadol , Male , Female , Humans , Adult , Middle Aged , Tramadol/therapeutic use , Airway Extubation , Cough/etiology , Cough/drug therapy , Bronchial Spasm/drug therapy , Laryngismus/drug therapy , Double-Blind Method
10.
JAAPA ; 35(10): 15-16, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36165542

ABSTRACT

ABSTRACT: Albuterol has been a cornerstone of asthma treatment for several decades, but evidence suggests that it may be overused at the expense of more efficacious treatment. Albuterol may not even be appropriate for sole first-line rescue medication in some patients. Inflammatory mechanisms have been shown to play a role early in the course of developing bronchospasm, suggesting that inhaled corticosteroids should be included as part of initial rescue treatment. Newer biologics target inflammatory cytokine pathways, which may be needed in patients with moderate to severe disease. Evidence-based recommendations for the management of asthma and bronchospasm are continuing to evolve.


Subject(s)
Asthma , Biological Products , Bronchial Spasm , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Albuterol/therapeutic use , Asthma/drug therapy , Biological Products/therapeutic use , Bronchial Spasm/drug therapy , Cytokines/therapeutic use , Humans
11.
Am J Respir Crit Care Med ; 201(2): 188-197, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31601120

ABSTRACT

Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.


Subject(s)
Aminophenols/therapeutic use , Aminopyridines/therapeutic use , Anti-Bacterial Agents/therapeutic use , Benzodioxoles/therapeutic use , Cystic Fibrosis/drug therapy , Nutritional Status , Quinolones/therapeutic use , Administration, Intravenous , Adolescent , Adult , Body Mass Index , Bronchial Spasm/chemically induced , Cough/chemically induced , Cystic Fibrosis/physiopathology , Deprescriptions , Drug Combinations , Dyspnea/chemically induced , Fatigue/chemically induced , Female , Forced Expiratory Volume , France , Gastrointestinal Diseases/chemically induced , Headache/chemically induced , Humans , Logistic Models , Male , Metrorrhagia/chemically induced , Multivariate Analysis , Myalgia/chemically induced , Product Surveillance, Postmarketing , Treatment Outcome , Young Adult
12.
BMC Pulm Med ; 21(1): 23, 2021 Jan 12.
Article in English | MEDLINE | ID: mdl-33435939

ABSTRACT

BACKGROUND: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in ß2-adrenergic agonist drug. CASE PRESENTATION: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission. CONCLUSION: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of ß2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.


Subject(s)
Acidosis, Lactic/chemically induced , Adrenergic beta-2 Receptor Agonists/adverse effects , Albuterol/adverse effects , Lactic Acid/blood , Status Asthmaticus/drug therapy , Acidosis/metabolism , Acidosis/therapy , Acidosis, Lactic/blood , Acidosis, Respiratory/metabolism , Acidosis, Respiratory/therapy , Adult , Bronchial Spasm/drug therapy , Bronchial Spasm/metabolism , Humans , Hypoxia/metabolism , Hypoxia/therapy , Male , Status Asthmaticus/metabolism , Ventilation-Perfusion Ratio
13.
Heart Surg Forum ; 24(3): E575-E577, 2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34173769

ABSTRACT

Severe bronchospasm during cardiopulmonary bypass is an unusual but potentially fatal event. No literature previously has reported such an event observed during surgery for type A aortic dissection. Herein, we report on a case of severe bronchospasm following cardiopulmonary bypass, during aortic surgery for type A aortic dissection. Bronchospasm did not respond to any conventional therapy, necessitating extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation thus serves as an alternative and effective therapy for refractory bronchospasm.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Bronchial Spasm/etiology , Extracorporeal Membrane Oxygenation/methods , Intraoperative Complications/etiology , Vascular Surgical Procedures/adverse effects , Aortic Dissection/diagnosis , Aortic Aneurysm, Thoracic/diagnosis , Bronchial Spasm/diagnosis , Bronchial Spasm/therapy , Bronchoscopy , Computed Tomography Angiography , Humans , Intraoperative Complications/diagnosis , Intraoperative Complications/therapy , Male , Middle Aged , Severity of Illness Index
14.
J Allergy Clin Immunol ; 146(5): 1152-1164.e13, 2020 11.
Article in English | MEDLINE | ID: mdl-32199913

ABSTRACT

BACKGROUND: Allergens elicit host production of mediators acting on G-protein-coupled receptors to regulate airway tone. Among these is prostaglandin E2 (PGE2), which, in addition to its role as a bronchodilator, has anti-inflammatory actions. Some patients with asthma develop bronchospasm after the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs, a disorder termed aspirin-exacerbated respiratory disease. This condition may result in part from abnormal dependence on the bronchoprotective actions of PGE2. OBJECTIVE: We sought to understand the functions of regulator of G protein signaling 4 (RGS4), a cytoplasmic protein expressed in airway smooth muscle and bronchial epithelium that regulates the activity of G-protein-coupled receptors, in asthma. METHODS: We examined RGS4 expression in human lung biopsies by immunohistochemistry. We assessed airways hyperresponsiveness (AHR) and lung inflammation in germline and airway smooth muscle-specific Rgs4-/- mice and in mice treated with an RGS4 antagonist after challenge with Aspergillus fumigatus. We examined the role of RGS4 in nonsteroidal anti-inflammatory drug-associated bronchoconstriction by challenging aspirin-exacerbated respiratory disease-like (ptges1-/-) mice with aspirin. RESULTS: RGS4 expression in respiratory epithelium is increased in subjects with severe asthma. Allergen-induced AHR was unexpectedly diminished in Rgs4-/- mice, a finding associated with increased airway PGE2 levels. RGS4 modulated allergen-induced PGE2 secretion in human bronchial epithelial cells and prostanoid-dependent bronchodilation. The RGS4 antagonist CCG203769 attenuated AHR induced by allergen or aspirin challenge of wild-type or ptges1-/- mice, respectively, in association with increased airway PGE2 levels. CONCLUSIONS: RGS4 may contribute to the development of AHR by reducing airway PGE2 biosynthesis in allergen- and aspirin-induced asthma.


Subject(s)
Aspergillosis/metabolism , Aspergillus fumigatus/immunology , Asthma, Aspirin-Induced/metabolism , Lung/pathology , Muscle, Smooth/metabolism , RGS Proteins/metabolism , Respiratory Mucosa/metabolism , Animals , Bronchial Spasm , Cells, Cultured , Dinoprostone/biosynthesis , Female , Humans , Male , Mice , Mice, Knockout , Muscle, Smooth/pathology , Prostaglandin-E Synthases/genetics , RGS Proteins/genetics , Signal Transduction
15.
J Perianesth Nurs ; 36(6): 612-614, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34736835

ABSTRACT

Adverse events associated with salvaged blood reinfusion are common, but bronchospasm has been rarely reported, especially in pediatrics. We report the case of a child undergoing epileptogenic focus resection, who experienced bronchospasm and kidney injury associated with reinfusion of salvaged blood, presumably related to excessive free hemoglobin.


Subject(s)
Arthroplasty, Replacement, Knee , Bronchial Spasm , Pediatrics , Blood Transfusion, Autologous , Bronchial Spasm/etiology , Child , Humans , Kidney
16.
Allergy ; 74(6): 1125-1134, 2019 06.
Article in English | MEDLINE | ID: mdl-30667530

ABSTRACT

BACKGROUND: The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR) and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility are scarce. OBJECTIVE: To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls. METHODS: A retrospective evaluation of the NACs conducted in our Unit for 2005-2017 and monitored by acoustic rhinometry and nasal-ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session [NAC-S & NAC-M]). The adverse events (AEs), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC-S performed at 1-2-month interval in AR, LAR and nonallergic rhinitis patients, and in healthy controls. RESULTS: A total of 11 499 NACs were performed in 518 children and 5830 adults. Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC-S performed in 710 subjects were 97.32%, 100%, and 92.91%, respectively. There were no false-positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes. CONCLUSION: The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma.


Subject(s)
Allergens/immunology , Nasal Provocation Tests/adverse effects , Nasal Provocation Tests/methods , Rhinitis, Allergic/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Allergens/administration & dosage , Asthma/diagnosis , Bronchial Spasm/etiology , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Retrospective Studies , Rhinometry, Acoustic , Young Adult
17.
Anaesthesia ; 74(3): 300-311, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30536369

ABSTRACT

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.


Subject(s)
Anesthesia , Perioperative Care , Adolescent , Bronchial Spasm/epidemiology , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Prospective Studies , Quality Improvement , Respiratory Sounds , United Kingdom
20.
Clin Med Res ; 17(1-2): 34-36, 2019 06.
Article in English | MEDLINE | ID: mdl-31160477

ABSTRACT

Cocaine can cause a myriad of changes in the lung, which can range from bronchoconstriction to destruction of the alveolar-capillary membrane and acute lung injury. Cocaine-induced bronchospasm is a diagnosis of exclusion that should be considered when the clinical presentation of acute hypoxic and hypercapneic respiratory failure cannot be explained by chronic obstructive pulmonary disease or asthma exacerbation, anaphylaxis to food or medications, exercise, or infection. Here, we present two patients with acute hypoxic and hypercapneic respiratory failure that was ultimately attributed to cocaine use shortly prior to symptom onset.


Subject(s)
Asthma , Bronchial Spasm , Cocaine/toxicity , Acute Disease , Asthma/chemically induced , Asthma/diagnosis , Asthma/physiopathology , Bronchial Spasm/chemically induced , Bronchial Spasm/diagnosis , Bronchial Spasm/physiopathology , Cocaine-Related Disorders/complications , Cocaine-Related Disorders/diagnosis , Cocaine-Related Disorders/physiopathology , Diagnosis, Differential , Female , Humans , Middle Aged
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