Probiotics combined with Budesonide and Ipratropium bromide for chronic obstructive pulmonary disease: A retrospective analysis.

To explore the effect of probiotics combined with budesonide and ipratropium bromide in the treatment of chronic obstructive pulmonary disease (COPD) on lung function and gut microbiota. This was a retrospective study of prospectively collected clinical data of 118 patients with COPD admitted to our hospital between January 2020 and December 2022. According to the treatment records, 59 patients received budesonide and irpratropium bromide (control group), and 59 patients received probiotics combined with budesonide and irpratropium bromide (observation group). The lung function, inflammatory factor levels, airway remodeling, and gut microbiota before and after treatment were compared between the 2 groups. After treatment, FVC, MMEF, PEF, and FEV1 in the 2 groups were higher than before treatment, and the values in the observation group were higher than those in the control group (P < .05). After treatment, the serum levels of TNF-α, IL-6, and PCT in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of serum MMP-9, VEGF, basic fibroblast growth factor, and NGF in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of lactobacilli and bifidobacteria in the 2 groups increased compared to those before treatment, and the observation group had a higher level, while the levels of Enterobacteriaceae and Enterococcus were lower in the observation group than those before treatment (P < .05). Based on budesonide and irpratropium bromide, probiotic treatment of COPD is more conducive to reducing the degree of inflammatory reactions, inhibiting airway remodeling, regulating the level of gut microbiota, and promoting the recovery of lung function.

Adherence to the asthma pathway, including pre-triage bronchodilator history, reduces hospitalizations.

Objective: To determine if adherence to an asthma treatment pathway is associated with a decrease in hospitalizations.Methods: A prospective cohort design was conducted of Thai children aged 2-15 years who visited the emergency department with severe asthma exacerbations, defined as a Buddhasothorn Asthma Severity Score ≥ 8. Patients who received systemic corticosteroids and nebulized short-acting beta-2 agonists combined with ipratropium bromides were classified as the adherence group. The timing of steroid and bronchodilator administration, length of hospital stay, and hospitalization rate were examined in relation to adherence to the asthma pathway. Multivariable logistic regression models and adjusted odds ratios were used to assess associations.Results: A total of 118 episodes of asthma exacerbations (EAEs) from 59 participants were included. Patients who adhered to the pathway had a significantly higher rate of systemic corticosteroid administration within 1 h of arrival at triage (88.6% vs. 41.9%, adjusted Odds Ratio: aOR 10.21; 95%CI 3.52-29.62). A higher proportion of the patients who adhered to the pathway also received inhaled ipratropium bromide ≥ 2 doses within 1 h of arrival at triage (72.7% vs. 12.2%, aOR 23.51; 95%CI 7.73-71.54) and it was administered significantly faster by 31 min (5 min vs. 36 min, p < 0.001) compared to non-adherence group. The hospitalization rate was significantly lower by almost half of EAEs for adherence group (36.4% vs. 63.5%, aOR 0.41; 95%CI 0.18-0.93).Conclusions: Accurate assessment of severity and adherence to the clinical pathway can reduce hospitalization in pediatric patients with severe asthma exacerbations.

Evaluation and Comparison of the Effectiveness of Atropine Eye Drops, Ipratropium Bromide Nasal Spray, and Amitriptyline Tablet in the Management of Clozapine-Associated Sialorrhea in Patients With Refractory Schizophrenia: A Randomized Clinical Trial.

PURPOSE: Clozapine, a second-generation antipsychotic medication, is mainly indicated for managing treatment-resistant schizophrenia. Among all the nonthreatening adverse effects of clozapine, sialorrhea is a stigmatizing complication occurring in approximately 31.0% to 97.4% of patients. In this study, 2 topical agents (atropine eye drop and ipratropium nasal spray) and a systemic medication (amitriptyline) were compared simultaneously for the management of clozapine-associated sialorrhea. METHODS: We conducted a randomized, single-blinded, non-placebo-controlled clinical trial from June 2022 to January 2023. Eligible patients were randomly allocated into 3 mentioned groups. Patients were monitored for sialorrhea weekly based on scales, including the Toronto Nocturnal Hypersalivation Scale, Clinical Global Impression-Improvement, and Clinical Global Impression-Severity for 1 month. Possible adverse drug reactions and adherence were also recorded. RESULTS: Twenty-four patients, including 6, 10, and 8 individuals in ipratropium bromide nasal spray, atropine eye drop, and amitriptyline groups, completed the study, respectively. The cohort's demographic, baseline clinical, and sociocultural characteristics were comparable among the 3 groups. Within-group comparisons, between times baseline and week 4, demonstrated that significant differences were in groups atropine and amitriptyline based on Toronto Nocturnal Hypersalivation Scale, in 3 groups based on Clinical Global Impression-Improvement, and also in only-atropine group based on Clinical Global Impression-Severity. Likewise, between-group comparisons showed that atropine was significantly more effective in clozapine-associated sialorrhea management than amitriptyline and ipratropium, in the first 2 weeks and second 2 weeks of study, respectively. Regarding safety, the interventions were tolerated relatively well. CONCLUSIONS: Conclusively, atropine is more efficacious than amitriptyline, within the first 2 weeks of study and also relative to ipratropium, overall. As time effect was significant between atropine and amitriptyline, according to analysis of covariance test, further investigation with longer follow-up duration would be prudent. In addition, expanding patient population with larger sample size should be conducted for more precision.

Atomization efficacy of a novel micro-dose mesh nebulizer (CVS-100) versus the traditional mesh nebulizer (M102) in adults with chronic obstructive pulmonary disease: A randomized non-inferiority clinical trial.

OBJECTIVE: To compare the atomization efficacy of a novel micro-dose mesh nebulizer (CVS-100) versus the traditional mesh nebulizer (M102) in nebulizing a combination of ipratropium bromide and salbutamol for treatment of stable moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: A randomized, parallel, non-inferiority study was conducted. A total of 64 stable COPD patients were randomly assigned to either the experimental group or the control group in a 1:1 ratio. Each the experimental group received nebulized Combivent (Compound Ipratropium Bromide Solution) with CVS-100, while the control group received Combivent with M102. Lung ventilation function was measured before and 30 min after nebulization, and the difference in percentage of forced expiratory volume in the first second (FEV1) of predicted value (FEV1%pred), the forced expiratory flow at 50% (FEF50%), the forced expiratory flow at 75% (FEF75%), the mid-expiratory flow (FEF25-75%), and maximal voluntary ventilation (MVV) was evaluated. The non-inferiority margin for the lower 95% confidence limit was set at 3.5%. RESULTS: The lower limit of the 95% confidence interval for the difference in FEV1%pred between the two groups was -1.83357, which was greater than -3.5. No significant differences were found in FEF50%, FEF75%, FEF25∼75%, MVV before and after nebulization between the two groups. CONCLUSION: The novel micro-dose mesh nebulizer (CVS-100) was found to be non-inferior to the traditional mesh nebulizer (M102) in terms of the change in FEV1%pred from baseline after nebulization. Similar results were observed for all other measures of efficacy.

Computer-aided design of muscarinic acetylcholine receptor M3 inhibitors: Promising compounds among trifluoromethyl containing hexahydropyrimidinones/thiones.

The new high selective mAChRs M3 inhibitors with IC50 in nanomolecular ranges, which can be the prototypes for effective COPD and asthma treatment drugs, were discovered with computational approaches among trifluoromethyl containing hexahydropyrimidinones/thiones. Compounds [6-(4-ethoxy-3-methoxy-phenyl)-4-hydroxy-2-thioxo-4-(trifluoromethyl)hexahydropyrimidin-5-yl]-phenyl-methanone (THPT-1) and 5-benzoyl-6-(3,4-dimethoxyphenyl)-4-hydroxy-4-(trifluoromethyl)hexahydropyrimidin-2-one (THPO-4) have been proved to be a highly effective (with IC50 values of 1.62 ⋅ 10-7  M and 3.09 ⋅ 10-9  M, respectively) at the same concentrations significantly competitive inhibit the signal conduction through mAChR3 in comparison with ipratropium bromide, without significant effect on mAChR2, nicotinic cholinergic and adrenergic receptors.

HPLC-UV/VIS for Determination of Ipratropium Bromide Mixed with Salbuterol, Beclomethasone Propionate and Budesonide using Dual Wavelength-Detection Method.

BACKGROUND: Inhalation preparation involves liquid or solid raw materials for delivering to lungs as aerosol or vapor. The liquid preparation for nebulizer is effective for convenient use and patient compliance and it has been extensively used in the treatment of clinical lung diseases. Clinical staff often mixes the compound ipratropium bromide with beclomethasone propionate and budesonide inhaler but reference values of inhalants for clinical use need to be established for simplifying the operation procedure. The high-performance liquid chromatography (HPLC) method of compound ipratropium bromide solution, beclomethasone propionate suspension and budesonide suspension after mixed atomization was studied. METHODS: The specificity, linearity, recovery (accuracy), precision and stability of compound ipratropium bromide, beclomethasone propionate and budesonide were tested to verify the developed liquid phase method. RESULTS: The developed liquid phase method had high specificity, linear R2≥0,999, recovery (accuracy) RSD (relative standard deviation) less than 2%, precision RSD less than 2,0%, and stability RSD less than 2,0%. CONCLUSION: The liquid phase methodology developed in this study can be used for the determination of compound ipratropium bromide mixed with beclomethasone propionate and budesonide. The current methodology can also be used to provide a reference for the determination of its content after mixing, and further data support for its clinical medication.

Quality of acute asthma care: an audit of clinical practice in a Victorian health service.

BACKGROUND: Gaps in the treatment of patients with acute asthma have been repeatedly described in Australia. We conducted a retrospective audit of acute asthma care at a Victorian tertiary institution. AIMS: To describe acute asthma care at a large health network in metropolitan Melbourne, and evaluate the extent to which Emergency Department (ED) care was consistent with National Asthma Council guidelines. METHODS: A retrospective audit was performed of medical records between July 2017 and June 2019. We included adult patients admitted to campuses within the Western Health network in Melbourne, Victoria, where the length of stay was at least 12 h, and the primary discharge diagnosis was asthma. RESULTS: Four hundred and ninety-three admissions were included in the analysis, representing 392 individual patients. Seventy-one percent of patients were female and 27% were current smokers. Ninety-six percent of patients had a prior asthma diagnosis, 63% had a previous hospital presentation and 75% were prescribed an inhaled preventer. In the ED, systemic corticosteroids and inhaled salbutamol were prescribed in 65% and 82% admissions respectively; adjunctive treatments included ipratropium (67% of admissions), magnesium sulfate (30%), adrenaline (11%) and non-invasive ventilation (9%). Overall, ED care was guideline concordant in 59% of admissions. On the wards, treatments prescribed within 24 h of admission included corticosteroids (90% of admissions), salbutamol (84%), ipratropium (64%) and inhaled preventers (63%). The proportion of patients prescribed these treatments, as well as documented follow up (e.g. asthma action plans), varied significantly depending on the treating specialty. CONCLUSION: The emergency treatment of patients with acute asthma frequently deviated from guidelines and there was significant variation in inpatient treatment. Quality improvement initiatives that incorporate structural changes are required to improve asthma care.

Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial.

BACKGROUND: Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking. OBJECTIVE: We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis. METHODS: Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2-3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications. RESULTS: We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan-Meier survival analysis for the median survival time of each arm with the usual care as the reference group. CONCLUSION: The symptomatic treatment evaluated has shown to be ineffective against cough.

Cough is the most frequent symptom reported by patients with lower respiratory tract infections. Despite being a defense mechanism, cough is unpleasant and negatively affects sleep and overall well-being. Accordingly, many patients with acute cough seek medical help to mitigate symptoms and reduce their duration despite the typically self-limiting nature of the condition. In this randomized clinical trial, we explored the benefit of 3 common symptomatic treatments recommended in some guidelines for relieving this symptom during the course of uncomplicated acute bronchitis, a cough suppressant, an inhaler, and honey intake. Although the total number of patients initially expected could not be achieved due to the disruption caused by the COVID-19 pandemic, the results of our study demonstrate a lack of efficacy of these products as the number of days of severe-to-moderate cough was similar in the 3 arms and comparable to the group of patients allocated to usual care.

Utilization of intranasal ipratropium bromide in the prevention of recurrent croup events: Is it effective?

OBJECTIVE: Recurrent croup (RC) is a common problem in the pediatric population. We theorize that reduced rhinorrhea and post-nasal drip as well as suppressed cough receptor activity by the anticholinergic, intranasal ipratropium bromide (IB), may lead to reduced inflammation and edema of the subglottis, decreasing RC symptoms. The aim of this study is to determine the effectiveness of IB in improving symptoms of RC and in reducing the need for alternative forms of management. METHOD: A retrospective chart review combined with survey data of patients with RC was conducted to assess demographic data, comorbidities, and treatment outcomes. Pediatric patients less than 10 years of age diagnosed with RC through the department of pediatric otolaryngology between 2018 and 2020 were included. Results were compared between one group treated with IB for RC and a second group treated with medications other than IB. RESULTS: Among the 67 patients treated for RC, 34 completed survey data and were included in the study. Overall, patients who were treated with IB for RC had 1.83 less croup episodes per year (p = 0.046), a 0.5-point improvement in child symptoms (p = 0.017) and 1.3 fewer doses of steroids per year than the patients not treated with IB (p = 0.018). Patients treated with IB were significantly more likely to answer "yes," that the use of medication helped improve symptoms (p < 0.01). CONCLUSION: Intranasal IB is a novel therapeutic option that may reduce RC events, improve patient symptoms and reduce steroid use. Further prospective studies are needed to definitively characterize the benefits of IB in the treatment of RC.

Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis.

Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the disease. A 74-year-old patient was admitted to the Department of Dermatology with purpura-like skin lesions on the upper, and lower extremities, including the buttocks. The lesions had appeared around the ankles 7 days before admission to the hospital and then started to progress upwards. The patient complained on lower limb paresthesia and pain. Other comorbidities included bronchial asthma, chronic sinusitis, ischemic heart disease, mild aortic stenosis, arterial hypertension, and degenerative thoracic spine disease. The woman had previously undergone nasal polypectomy twice. She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 µg per day, and ipratropium bromide 20 µg per day. Ten days prior to admission, she was commenced on torasemide at a dose of 50 mg per day prescribed by a general practitioner due to high blood pressure. Doppler ultrasound upon admission to the hospital excluded deep venal thrombosis. The laboratory tests revealed leukocytosis (17.1 thousand per mm3) with eosinophilia (38.6%), elevated plasma level of C-reactive protein (119 mg per L) and D-dimers (2657 ng per mm3). Indirect immunofluorescent test identified a low titer (1:80) of antinuclear antibodies, but elevated (1:160) antineutrophil cytoplasmic antibodies (ANCA) in the patient's serum. Immunoblot found them to be aimed against myeloperoxidase (pANCA). A chest X-ray showed increased vascular lung markings, while high-resolution computed tomography revealed peribronchial glass-ground opacities. Microscopic evaluation of skin biopsy taken from the lower limbs showed perivascular infiltrates consisting of eosinophils and neutrophils, fragments of neutrophil nuclei, and fibrinous necrosis of small vessels. Electromyography performed in the lower limbs because of their weakness highlighted a loss of response from both sural nerves, as well as slowed conduction velocity of the right tibial nerve and in both common peroneal nerves. Both clinical characteristics of skin lesions and histopathology suggested a diagnosis of EGPA, which was later confirmed by a consultant in rheumatology. The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day. The treatment resulted in a gradual regression of skin lesions within a few weeks. The first report of EGPA dates back to 1951. Its authors were Jacob Churg and Lotte Strauss. They described a case series of 13 patients who had severe asthma, fever, peripheral blood eosinophilia, and granulomatous vasculitis in microscopic evaluation of the skin. Three histopathological criteria were then proposed, and Churg-Strauss syndrome was recognized when eosinophilic infiltrates in the tissues, necrotizing inflammation of small and medium vessels, and the presence of extravascular granulomas were observed together in a patient (1). Only 17.4% of patients met all three histopathological criteria, and the diagnosis of the disease was frequently delayed despite of its overt clinical picture (2). In 1984, Lanham et al. proposed new diagnostic criteria which included the presence of bronchial asthma, eosinophilia in a peripheral blood smear >1.5 thousand per mm3, and signs of vasculitis involving at least two organs other than the lungs (3). Lanham's criteria could also delay the recognition of the syndrome before involvement of internal organs, and the American College of Rheumatology therefore established classification criteria in 1990. These included the presence of bronchial asthma, migratory infiltrates in the lungs as assessed by radiographs, the presence of abnormalities in the paranasal sinuses (polyps, allergic rhinitis, chronic inflammation), mono- or polyneuropathy, peripheral blood eosinophilia (>10% of leukocytes must be eosinophils), and extravascular eosinophilic infiltrates in a histopathological examination. Patients who met 4 out of 6 criteria were classified as having Churg-Strauss syndrome (4). The term EGPA was recommended to define patients with Churg-Strauss syndrome in 2012 (5). EGPA is a condition with low incidence (0.11-2.66 cases per million) and morbidity. It usually occurs in the fifth decade of life (6,7), although 65 cases reports of EGPA in people under 18 years of age could be found in the PubMed and Ovid Medline Database at the end of 2020 (8). The etiopathogenesis of the disease has not been fully explained so far. Approximately 40-60% of patients are positive to pANCA (9), but the role of these antibodies in the pathogenesis of EGPA remains unclear. They are suspected to mediate binding of the Fc receptor to MPO exposed on the surface of neutrophils. Subsequently, this may active neutrophils and contribute to a damage of the vascular endothelium (9,10). Glomerulonephritis, neuropathy, and vasculitis are more common in patients with EGPA who have detectable pANCA when compared with seronegative patients. There are at least several drugs which potentially may EGPA. The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13). Although no relationship has been demonstrated so far between the occurrence of EGPA and the intake of drugs from the groups used by the presented patient, a clear time relationship can be observed between the commencement of torasemide and the onset of symptoms in our patient. To date, only three cases of leukocytoclastic vasculitis have been reported after the administration of torasemide. Both of them developed cutaneous symptoms of the disease within 24 hours of the administration of torasemide in patients with no previous history of drug hypersensitivity, but they disappeared quickly within 8-15 days after drug discontinuation (14,15). The chemical structure of torasemide is similar to the molecule of sulfonamides which were previously found to be a triggering factors for EGPA (12). This drug belongs to the group of loop diuretics classified as sulfonamide derivatives. A comparison of the chemical structure of torasemide and sulphanilamide molecules is presented in Figure 1. The clear time relationship between starting the administration of torasemide and the occurrence of purpura-like lesions suggests that it was an aggravating factor for EGPA in our patient. A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible inducing factor for the development of vascular purpura in patients suffering from EGPA but without previous cutaneous involvement.

Magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease, often punctuated by recurrent flare-ups or exacerbations. Magnesium sulfate, having a bronchodilatory effect, may have a potential role as an adjunct treatment in COPD exacerbations. However, comprehensive evidence of its effects is required to facilitate clinical decision-making. OBJECTIVES: To assess the effects of magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease in adults. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) trials portal, EU Clinical Trials Register and Iranian Registry of Clinical Trials. We also searched the proceedings of major respiratory conferences and reference lists of included studies up to 2 August 2021. SELECTION CRITERIA: We included single- or double-blind parallel-group randomised controlled trials (RCTs) assessing magnesium sulfate in adults with COPD exacerbations. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. The primary outcomes were: hospital admissions (from the emergency room); need for non-invasive ventilation (NIV), assisted ventilation or admission to intensive-care unit (ICU); and serious adverse events. Secondary outcomes were: length of hospital stay, mortality, adverse events, dyspnoea score, lung function and blood gas measurements. We assessed confidence in the evidence using GRADE methodology. For missing data, we contacted the study investigators. MAIN RESULTS: We identified 11 RCTs (10 double-blind and 1 single-blind) with a total 762 participants. The mean age of participants ranged from 62 to 76 years. Trials were single- or two-centre trials conducted in Iran, New Zealand, Nepal, Turkey, the UK, Tunisia and the USA between 2004 and 2018. We judged studies to be at low or unclear risk of bias for most of the domains. Three studies were at high risk for blinding and other biases.  Intravenous magnesium sulfate versus placebo Seven studies (24 to 77 participants) were included. Fewer people may require hospital admission with magnesium infusion compared to placebo (odds ratio (OR) 0.45, 95% CI 0.23 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) = 7; 3 studies, 170 participants; low-certainty evidence). Intravenous magnesium may result in little to no difference in the requirement for non-invasive ventilation (OR 0.74, 95% CI 0.31 to 1.75; very low-certainty evidence). There were no reported cases of endotracheal intubation (2 studies, 107 participants) or serious adverse events (1 study, 77 participants) in either group. Included studies did not report intensive care unit (ICU) admission or deaths. Magnesium infusion may reduce the length of hospital stay by a mean difference (MD) of 2.7 days (95% CI 4.73 days to 0.66 days; 2 studies, 54 participants; low-certainty evidence) and improve dyspnoea score by a standardised mean difference of -1.40 (95% CI -1.83 to -0.96; 2 studies, 101 participants; low-certainty evidence). We were uncertain about the effect of magnesium infusion on improving lung function or oxygen saturation. For all adverse events, the Peto OR was 0.14 (95% CI 0.02 to 1.00; 102 participants); however, the event rate was too low to reach a robust conclusion.  Nebulised magnesium sulfate versus placebo Three studies (20 to 172 participants) were included. Magnesium inhalation may have little to no impact on hospital admission (OR 0.77, 95% CI 0.21 to 2.82; very low-certainty evidence) or need for ventilatory support (NIV or mechanical ventilation) (OR 0.33, 95% CI 0.01 to 8.20; very low-certainty evidence). It may result in fewer ICU admissions compared to placebo (OR 0.39, 95% CI 0.15 to 1.00; very low-certainty evidence) and improvement in dyspnoea (MD -14.37, 95% CI -26.00 to -2.74; 1 study, 20 participants; very low-certainty evidence). There were no serious adverse events reported in either group. There was one reported death in the placebo arm in one trial, but the number of participants was too small for a conclusion. There was limited evidence about the effect of magnesium inhalation on length of hospital stay, lung function outcomes or oxygen saturation. Included studies did not report adverse events.  Magnesium sulfate versus ipratropium bromide  A single study with 124 participants assessed nebulised magnesium sulfate plus intravenous magnesium infusion versus nebulised ipratropium plus intravenous normal saline. There was little to no difference between these groups in terms of hospital admission (OR 1.62, 95% CI 0.78 to 3.37), endotracheal intubation (OR 1.69, 95% CI 0.61 to 4.71) and length of hospital stay (MD 1.10 days, 95% CI -0.22 to 2.42), all with very low-certainty evidence. There were no data available for non-invasive ventilation, ICU admission and serious adverse events. Adverse events were not reported.  AUTHORS' CONCLUSIONS: Intravenous magnesium sulfate may be associated with fewer hospital admissions, reduced length of hospital stay and improved dyspnoea scores compared to placebo. There is no evidence of a difference between magnesium infusion and placebo for NIV, lung function, oxygen saturation or adverse events. We found no evidence for ICU admission, endotracheal intubation, serious adverse events or mortality. For nebulised magnesium sulfate, we are unable to draw conclusions about its effects in COPD exacerbations for most of the outcomes. Studies reported possibly lower ICU admissions and a lesser degree of dyspnoea with magnesium inhalation compared to placebo; however, larger studies are required to yield a more precise estimate for these outcomes. Similarly, we could not identify any robust evidence for magnesium sulfate compared to ipratropium bromide. Future well-designed multicentre trials with larger samples are required, including subgroups according to severity of exacerbations and COPD phenotypes.

Comparison efficacy of randomized nebulized magnesium sulfate and ipratropium bromide/fenoterol in children with moderate to severe asthma exacerbation.

BACKGROUND: In Thailand, nebulized ipratropium bromide/fenoterol, is commonly used in addition to salbutamol for severe asthma exacerbation. Recently, nebulized MgSO4 is indicated in GINA 2015 as an additive treatment for severe cases. However, there is limited data showed the efficacy of both drugs in childhood severe asthma. The purpose of this study to compare efficacy and safety of nebulized MgSO4 and ipratropium bromide/fenoterol in moderate to severe asthma attacks. METHODS: In this a prospective, double-blind, randomized, controlled trial study, we enrolled thirty-three children, age ranged from 2 to 15 years old, with PRAM score ≥ 4 (moderate to severe asthma exacerbation) despite 3 doses of nebulized salbutamol. Each patient was randomized to receive either three doses of nebulized MgSO4 or nebulized ipratropium bromide/fenoterol every 30 minutes. The PRAM score was measured at 0, 30, 60, 90, 120 and 240 minutes after the treatment. The adverse event and admission days were also evaluated. RESULTS: Sixteen patients received nebulized MgSO4 and seventeen received nebulized ipratropium bromide/fenoterol. Almost patients were classified as having moderate asthmatic attack. There were no statistically significant difference between the two study groups in almost baseline characteristic, PRAM score at 0, 30, 60, 90, 120, 240 minutes. The hospital length of stay was also similar between two groups (p = 0.83). There were no serious events in both groups. CONCLUSIONS: Our double blind, randomized, controlled pilot study demonstrated non-inferior outcomes including clinical benefit and safety of nebulized MgSO4 and nebulized ipratropium bromide/fenoterol among Thai children with acute moderate asthmatic.

The use of ipratropium bromide for treating moderate to severe asthma exacerbations in pediatric patients in an emergency setting: A cost-effectiveness analysis.

OBJECTIVES: Although the efficacy of the addition of ipratropium bromide (IB) to short-acting ß2-agonists (SABAs) for treating children with moderate to severe asthma exacerbations has been demonstrated, evidence of its cost-effectiveness is scarce. The aim of the present study was to evaluate the cost-effectiveness of treatment with a combination of SABAs and IB compared with SABAs alone for the treatment of children with moderate to severe asthma exacerbations. METHODS: To achieve the objectives of the study, a decision-analysis model was adapted. Effectiveness parameters were obtained from a systematic review of the literature with meta-analysis. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission. RESULTS: In children with moderate to severe asthma exacerbations, the base-case analysis showed that compared to SABAs alone, treatment with a combination of SABAs and IB was associated with lower overall treatment costs (US$126.24 vs. US$170.69 mean cost per patient) and a higher probability of hospital admission avoided (0.7999 vs. 0.7100), thus leading to dominance. For children with severe asthma exacerbations, these values were US$132.99 versus US$170.69 and 0.7883 versus 0.7100, respectively. CONCLUSIONS: In Colombia, when compared to therapy with SABAs alone, therapy with a combination of SABAs and IB for treating pediatric patients with moderate to severe asthma exacerbations involves a lower probability of hospital admission at lower treatment costs.

Asthma and COPD medicines prescription-claims: A time-series analysis of England's national prescriptions during the COVID-19 pandemic (Jan 2019 to Oct 2020).

BACKGROUND: During the pandemic, there have been disruptions to how patients seek care. RESEARCH DESIGN AND METHODS: To investigate monthly prescription claims for asthma and chronic obstructive pulmonary disease (COPD) medicines during the first UK wave, interrupted time series (ITS) analysis was used. A national cohort of community patients' data were examined. RESULTS: Descriptive statistics show salbutamol, aminophylline, ipratropium, and theophylline remain below pre-pandemic levels.Montelukast showed pre-pandemic monthly increase (Est. 67,151 doses, P = 0.05, 95% CI: 1011, 133,291), followed by a jump of 1.6 million doses at March , followed by monthly declines (Est. -112,098 doses, P = 0.216, 95% CI: -293,499, 69,303).Before the pandemic, tiotropium, salbutamol, aminophylline, and ipratropium (P = 0.003) show monthly declines but theophylline and beclometasone showed increases. In March , salbutamol (P = 0.033) and ipratropium (P = 0.001) show a significant jump. After March , ipratropium continues with a downward trajectory (P = 0.001), with a generalized negative trend for all other agents. Salbutamol confidence bounds become negative after March 2020. Some brands were unavailable. CONCLUSIONS: An 'unmet' medical gap is identified. While it is essential to understand the underlying reasons, urgent action needs to be taken to reassess patients and ensure continuity of care.PLAIN LANGUAGE SUMMARIES (PLS)Asthma and chronic obstructive pulmonary disease (COPD) are long-term lung conditions, affecting 6 million & 1.2 million people respectively and causing breathing difficulties. Sufferers are at a higher risk of chest infections including the coronavirus. Regular use of prescribed medication stabilizes these conditions and prevents them from getting worse. It is common to be prescribed a combination of five to eight oral and inhaled medications.We investigated the impact of the pandemic on the dispensing of these specific medicines across England during the first wave. The English Prescribing Dataset was checked from January 2019 to February 2020 (14 months before the pandemic) and March to October 2020 (8 months after its onset).We find that since March 2020, salbutamol, aminophylline, ipratropium, and theophylline have not returned to their pre-pandemic levels. However, for all agents, there is great variability. Further analysis suggests these trends are not reversing, suggesting that people have not been using their medication as anticipated for 8 months, which is concerning.As a consequence of this work, we recommend that doctors specifically call these patients and discuss their health as a matter of urgency, we encourage patients to continue to take their medication. We advise policy changes to waive the NHS prescription levy for asthma and COPD medication and we seek more granular data for further harm quantification. There are several strengths and weaknesses to our analysis, and we need to conduct more studies to ask patients about their experiences.

Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis.

BACKGROUND: A combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice. OBJECTIVE: To evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents. METHODS: The MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the earliest record date to September 2020 for randomized controlled trials in children and adolescents (≤18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO. RESULTS: Of the 1061 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66-0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.73; 95% CI 0.60-0.88; p = 0.0009; I2 = 4%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50-0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63-4.98). CONCLUSION: IB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. The very low to high quality of evidence indicated that future well-designed double-blind RCTs with large sample are needed for research on evaluating the effectiveness of IB + salbutamol treatment for asthma in children and adolescents.

A Statewide Study of the Epidemiology of Emergency Medical Services' Management of Pediatric Asthma.

OBJECTIVES: Little is known about emergency medical services' (EMS') management of pediatric asthma. This study's objective was to describe the demographic, clinical, and geographic characteristics of current EMS' management of pediatric asthma in the state with the fourth-largest pediatric population. METHODS: This was a retrospective observational study of EMS patients ages 2 to 18 years with an asthma exacerbation from 2011 to 2016. Patients from Florida's EMS Tracking and Reporting System were included if their EMS chief complaint indicated respiratory distress, if they received at least 1 albuterol treatment, and if they were transported to a hospital. RESULTS: A total of 11,226 patients met the inclusion criteria. The median age was 9 years, and 49% were African-American. Geospatial analysis revealed 4 rural counties with disproportionate numbers of African-American patients. In addition to albuterol, 37% of patients received ipratropium bromide and 9% received systemic corticosteroids. Adjusted logistic regression revealed that the strongest predictors of receiving systemic corticosteroids from EMS were intravenous access (odds ratio, 33.4; 95% confidence interval, 24.4-45.6) and intravenous magnesium sulfate administration (odds ratio, 5.0; 95% confidence interval, 3.4-7.3), indicating a more severe presentation. CONCLUSIONS: This statewide study demonstrated low rates of EMS administration of ipratropium bromide and systemic corticosteroids, both evidence-based treatments for asthma exacerbations. Targeted EMS education should attempt to increase utilization of both those medications. In addition, the feasibility and efficacy of EMS administration of oral systemic corticosteroids for children should be explored.

Case report: Paradoxical responses to short acting beta-agonists in a pediatric patient.

Introduction: Asthma is one of the most common airway diseases that nearly all pediatricians will encounter in their clinical practice. Using spirometry to compare a patient's forced expiratory volume in one second (FEV1) both pre- and post-bronchodilator administration is the ideal way to document a paradoxical bronchodilator response.Case Study: Here, we present a patient who experienced paradoxical responses to short acting beta-2 agonists (SABAs; albuterol and levalbuterol).Results: This patient responded to an anti-cholinergic agent (ipratropium bromide) with both subjective as well as objective response.Conclusion: This case highlights the need to include paradoxical response to SABAs in the differential of a patient with poorly controlled asthma. It also provides an example of successful treatment of a pediatric patient with a class of medications previously reserved for adults with chronic obstructive pulmonary disease.

Variability in care for children with severe acute asthma in Latin America.

BACKGROUND: Care variability for children with severe acute asthma has been well documented in high-income countries, yet data from low- and middle-income regions are lacking. We sought to characterize the magnitude of practice variability in the care of Latin American children to identify opportunities for standardization of care. METHODS: A cross-sectional study performed through a retrospective analysis of contemporaneously collected data of children with severe acute asthma admitted to a center contributing to the LARed Network registry between May 2017 and May 2019. Centers were grouped by geographic location: Atlantic (AT), South Pacific (SP), and North Central (NC). RESULTS: Among 434 children, most received care in hospitals in the AT group (54% [235/434]), followed by the NC (23% [101/434]) and SP (23% [98/434]) groups. The majority of children in the AT (92% [215/235]) and SP (91% [89/98]) groups received nebulized salbutamol/albuterol, while metered-dose inhalers were preferred in the NC group (72% [73/101]). There was a wide variation in the use of antibiotics: AT (57% [135/235]), SP (48% [47/98]), and NC (14% [14/101]). The same was true for ipratropium bromide: AT (67% [157/235]), SP (90% [88/98]), and NC (17% [17/101]), and aminophylline: AT (57% [135/235]), NC (5% [5/101]), and SP (0% [0/98]). High-flow nasal cannula was the preferred respiratory support modality in the AT (60% [141/235]) and NC (40% [40/101]) groups, while bilevel positive airway pressure (BiPAP) use was more common in the SP group (80% [78/98]). CONCLUSION: We identified significant variability in care for severe acute asthma. Our findings will help to inform the design of future studies, quality improvement initiatives, and development of practice guidelines within Latin America.

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT01429415.