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Background: Dyspnea is a complex symptom of chronic obstructive pulmonary disease (COPD) which is not strongly correlated with lung function measures. Long-acting bronchodilators (LAB) may reduce this dyspnea, but some patients report persistent chronic dyspnea despite this treatment. This study aims to assess residual reversibility and clinical response after short-acting bronchodilator (SAB) in COPD patients already treated by LAB and reporting persistent dyspnea., Methods: COPD patients with a persistent dyspnea (modified Medical Research Council scale (mMRC) ≥1) despite current stable treatment with at least one LAB were included. Spirometry, plethysmography and impulse oscillometry (IOS) were performed at peak effect of their LAB and repeat 45 min after the intake of two SAB (400 µg of salbutamol and 80 µg of ipratropium). Dyspnea improvement was assessed at 45 min after SAB through a comparative two-sided VAS (-100 mm for maximal improvement; +100 mm for maximal degradation)., Results: Twenty-two COPD patients were analyzed, mainly men (59.1 %) with a mean age of 60.6 years and a median FEV1 of 54 % of predicted values. Fifty percent of patients reported a severe basal dyspnea (mMRC ≥2). After SAB, spirometric and plethysmographic measurements were statistically improved. For IOS measurement, reactance at 5 Hz (X5) and area of reactance (AX) were also improved. Fifty percent of patients reported a clinically relevant improvement of their resting dyspnea. However, no correlation was found between dyspnea improvement and functional measures., Conclusions: Fifty percent of COPD patients regularly treated with one or two LAB still report a relevant improvement of resting dyspnea after the adjunctive intake of double short-acting bronchodilators. Physiological mechanisms associated with this improvement remain to be determined., Clinical Trial Registration: NCT02928744., Competing Interests: Declaration of Competing Interest OLR reports personal fees from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, and non-financial supports from AstraZeneca, Boehringer Ingelheim, Chiesi, Correvio, GlaxoSmithKline, Mayoli, MSD, Mylan, Novartis, Pfizer, PulmonX, Santelys Association, Vertex and Zambon, unrelated to the submitted work. MP reports non-financial supports from Boehringer Ingelheim, GlaxoSmithKline, Sanofi Aventis France and Sysmed, unrelated to the submitted work. HS reports non-financial support from GlaxoSmithKline, LVL médical, Oxyvie, unrelated to the submitted work. NB reports personal fees from AstraZeneca, and non-financial support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKlein, Novartis, Santelys association, SOS oxygène and Teva, unrelated to the submitted work. PD reports personnal fees and non-financial support from ALK, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis, Sanofi and Stallergènes, unrelated to the submitted work. TP reports grants from AstraZeneca, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and congress support from AstraZeneca, GlaxoSmithKlein, Novartis and Chiesi, unrelated to the submitted work., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

Objective: This retrospective review documents the experience of ipratropium bromide use among pediatric patients with sialorrhea at our multidisciplinary sialorrhea clinic at Children's Hospital at London Health Sciences Centre (LHSC)., Methods: A retrospective chart review of patients diagnosed with sialorrhea at our multidisciplinary clinic between January 2015 and June 2021 was completed. Data on patient demographics, comorbidities, clinical presentation, previous interventions, quality of life, and medication adverse side effects was collected. Drooling Frequency and Severity Scale (DFSS) scores were reviewed to compare sialorrhea management pre- and post-treatment with topical 0.03% ipratropium bromide nasal solution. A descriptive analysis and Wilcoxon signed rank tests were conducted to compare pre- versus post-treatment DFSS scores., Results: A total of 12 patients presented for follow-up and were included in the final analysis. At the pre-treatment visit, the median DFSS score was 4 for frequency and 5 for severity. Post-treatment, median DFSS score was 3 for frequency and 4.5 for severity, ( P  = .020 and .129, respectively). Minimal adverse effects were encountered., Conclusions: Ipratropium bromide provided a statistically significant benefit for drooling frequency in the patients studied and may present an additional topical medical option for pediatric sialorrhea with limited adverse effects., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Ethnopharmacological Relevance: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory respiratory disease. Citrus Reticulata peel, the dried ripe peel of Citrus Reticulata species, has been found to have anti-inflammatory and cough attenuation effects. However, the therapeutic effects and its precise underlying mechanisms of atomizing inhalation using Citrus Reticulata essential oil (CREO) have not yet been fully elucidated., Aim of the Study: The aim of this study was to assess the therapeutic effects of Citrus Reticulata essential oil and its associated anti-inflammatory mechanisms in COPD rat model., Methods: A total of 80 SD rats were randomized into four groups: control group (Con), COPD model group (COPD), COPD + ipratropium bromide (IB), and COPD + citrus reticulata essential oil (CREO). To induce COPD in rats, cigarette smoke (CS) exposure was used, while CREO and IB groups were administered through atomizing inhalation. The clinical signs, pathological lesions of the lung, percentages of antigen-presenting lung macrophages (CD11b/c + /CD86 + cells) and CD8 + T cells, and the content and mRNA expression of cytokines of the lung were analyzed., Results: The findings revealed that atomizing inhalation of Citrus reticulata essential oil had therapeutic effects on COPD rats. The treatment resulted in improvement in the body weight and mental status of COPD rats, reduced pathological injury of the lung, and increased proportion of CD11b/c + /CD86 + cells in lung macrophages, while also decreasing the number of CD8 + T cells. In addition, the Citrus Reticulata essential oil reduced the contents of IL-18, IL-17A, IL-12p70, and GM-CSF, downregulated the relative mRNA expression of IFN-γ, IL-4, and MMP-12, and upregulated the mRNA expression of IL-10., Conclusions: Citrus reticulata essential oil can alleviate histological injury of the lung and regulate macrophages and CD8 + T cells in COPD rats. The study suggests that citrus reticulata essential oil could be a potential therapeutic agent for COPD., Competing Interests: Declaration of competing interest Xi Peng and Qiaobo Ye: Conceptualization, Supervision, Project administration and Funding acquisition. Qing Deng and Juan Wang: Methodology and Investigation. Zhengqiang Yu, Jiajia Deng, Zhenhua Sun, Zhen Ye and Kaihua Qin:Resources. Changlin Wen and Zhengqiang Yu:Investigation and Formal analysis. Xi Peng, Changlin Wen, Zhengqiang Yu and Qiaobo Ye andWriting - Original Draft and Visualization. All authors contributed to perform the fundamental experiments and approve the final submitted version of the manuscript. All the authors report no conflicts of interest in this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest All the authors declared there are no competing financial interests in relation to the work described., (Copyright © 2023. Published by Elsevier Ltd.)

The new high selective mAChRs M3 inhibitors with IC 50 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 IC 50 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., (© 2023 Wiley-VCH GmbH.)

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., Competing Interests: The authors declare that they have no confl ict of interest., (Thieme. All rights reserved.)

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., (© 2022 Royal Australasian College of Physicians.)

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., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022. Published by Elsevier B.V.)

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.

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., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

Objectives: Although the efficacy of the addition of ipratropium bromide (IB) to short-acting β2-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., (© 2021 Wiley Periodicals LLC.)

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.

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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., (© 2020 Wiley Periodicals LLC.)

Objective: To test the effects of inhaled ipratropium on clinical outcomes of critical asthma in the first randomized trial of this adjunctive therapy in critically ill children., Design: Pilot, placebo-controlled, double-blinded, and randomized-controlled trial PATIENTS: Thirty children (15 per group) with critical asthma receiving high-intensity albuterol per a standardized pathway utilizing objective assessments to wean patients to less frequent albuterol administration., Interventions: Subjects were randomized to receive either nebulized ipratropium bromide (500 µg in 0.9% saline per dose) or an equivalent volume of nebulized 0.9% saline every 6 h until the patient was successfully weaned to albuterol doses every 2 h ("q2 albuterol")., Measurements and Main Results: Demographics, initial clinical severity score, and asthma histories were similar between groups. There was no significant difference in the median duration of high-intensity albuterol between the treatment group (17.5 [10.3-22.1] h) and placebo group (14.6 [12.7-24.5] days; p = .56). Similarly, there was no significant difference in pediatric intensive care unit length of stay (22.6 [21.1-33.6] vs. 21.4 [16.1-35.8] h; p = .74) or hospital length of stay (48.0 [41.8-59.8] vs. 47.3 [37.2-63.1] h; p = .67). In multivariate linear regression adjusting for identified confounders, treatment with ipratropium was not significantly associated with any of the three outcomes. Side effects were rare and occurred with equally between both groups CONCLUSIONS: Adjunctive therapy with ipratropium was not associated with decreased duration of high-intensity albuterol or shortened length of stay when compared to placebo. A larger, multicenter trial is warranted to confirm that ipratropium does not improve clinical outcomes., (© 2020 Wiley Periodicals LLC.)

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.

Introduction: Postoperative pulmonary complications (PPCs) are common and associated with increased morbidity, mortality, and medical cost. They are gaining increasing concerns among patients receiving neurological surgery. Chronic obstructive pulmonary disease (COPD) affect a large section of whole population and is also one of the risk factors of PPCs in the perioperative setting. Ipratropium bromide is the inhalation solution for the treatment of COPD. Studies showed the perioperative nebulization of ipratropium bromide could increase the lung function and decrease the incidence of postoperative pneumonia in COPD patients underwent thoracic surgery. The purpose of this study is to investigate the effect of perioperative nebulization of ipratropium bromide on PPCs in COPD patients underwent neurosurgical surgery., Methods and Analysis: This study is a multicenter retrospective study in China. Patients who meet the inclusion/exclusion criteria are selected from 7 neurosurgical centers in China. According to whether ipratropium bromide is used in perioperative period, the patients are divided into exposure group and control group. The primary outcome is the incidence of postoperative pneumonia. Secondary outcomes are unplanned intubation, postoperative mechanical ventilation ≥ 48 hours, respiratory failure, atelectasis, death, and length of stay., Ethics and Dissemination: This study was approved by the ethics committee (EC) of the School of Public Health, Fudan University, Shanghai, China. Waived by the ethics committee, no written consent form was obtained since we used the registry data. The study results will be communicated via publication., Trial Registration Number: ChiCTR1900022552.

Objectives: To characterize the clinical course and outcome of children with status asthmaticus (SA) admitted to a pediatric intensive care unit (PICU) METHODS: All patients with SA who were admitted to a PICU from January 2003 to December 2018 were reviewed. Polymerase chain reaction (PCR) studies on nasopharyngeal aspirate for respiratory pathogens were performed from 2014 to 2018., Results: Sixty-seven SA admissions constituted 2.4% of total PICU admissions (n = 2788). Fifteen (22.4%) children required noninvasive ventilation (NIV), while 7 children (10%) required invasive mechanical ventilation. Nonadherence to prior asthma therapy was common. PCR was positive for enterorvirus/rhinovirus in 84% (16 out of 19) and for any virus in 95% of nasopharyngeal aspirate (NPA) samples of patients between 2014 and 2018. Over the 16-year period, increased utilization of ipratropium bromide, magnesium sulfate and NIV was noted (P < .05). Patients who required invasive mechanical ventilation had significantly higher heart rate, lower pH and longer PICU length of stay (LOS) when compared to nonintubated children (P < .05). There was no mortality, gender difference, or seasonal characteristics in these SA admissions. Median LOS in PICU was 2 days (interquartile range 1-3 days)., Conclusions: SA accounts for a small proportion of PICU admissions. LOS was short and prognosis generally good. Nonadherence to prior asthma therapy was common. The most common trigger is enterovirus/rhinovirus for children with severe asthma requiring PICU admission. A trend of increase in usage of ipratropium, magnesium sulfate and NIV was observed. Primary prevention and early treatment of exacerbation are the most important step in managing children with asthma. Regular follow-up to ensure compliance together with annual vaccination could possibly avoid PICU admissions., (© 2020 John Wiley & Sons Ltd.)

Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy. It is a medical emergency that requires immediate recognition and treatment. Albuterol in combination with ipratropium bromide in the emergency department (ED) has been shown to decrease the time spent in the ED and the hospitalization rates. The benefits of ipratropium are not sustained after admission to the hospital. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6 to 12 hours. Viral respiratory infections are a common trigger for acute asthma; other causes include medical nonadherence, allergen exposure (especially pets and mold [e.g., Alternaria species]) in individuals who are severely atopic, nonsteroidal anti-inflammatory exposure in patients with aspirin allergy, irritant inhalation (e.g., smoke, paint), exercise, and insufficient use of inhaled or oral corticosteroids. The patient's history should focus on the acute assessment of asthma control and morbidity, including current use of oral or inhaled corticosteroids; the number of hospitalizations, ED visits, intensive care unit admissions, and intubations; the frequency of albuterol use; the presence of nighttime symptoms; activity intolerance; current medications; exposure to allergens; and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, difficulty speaking, refusal to recline < 30°, a pulse of >120 beats/min, and decreased breath sounds. More objective measures of airway obstruction via peak flow or forced expiratory volume in 1 second and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values of >90% are reassuring, although CO₂ retention and a low partial pressure of oxygen may be missed.

To observe the clinical efficacy of aerosol inhalation of ipratropium bromide and terbutaline on the patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). A total of 136 COPD patients with acute exacerbation were divided into the ipratropium bromide group (n=69) and the terbutaline group (n=67). Patients in the ipratropium bromide group were required to take ipratropium bromide, while those in the terbutaline group took terbutaline for 3 days. Then, changes in symptoms, vital signs, blood-gas indicators and pulmonary functions were compared and analyzed between two groups. In ipratropium bromide group, patients with amelioration in vital signs and symptoms, especially for the symptom of coughing (P<0.01), were more than those in the terbutaline group, with statistically significant difference (P<0.05). In addition, following medication, analysis showed that the improvement in the blood-gas indicators and pulmonary functions in the ipratropium bromide was excellent in comparison with the terbutaline group, especially the improvement in the pulmonary ventilation function (P<0.01). Comparison over the incidence rates of adverse events in the ipratropium bromide group and terbutaline group showed an evident difference (P<0.05). For treatment of patients with acute exacerbation of COPD, aerosol inhalation of ipratropium bromide is a safe but effective method.

Purpose: Ipratropium and salmeterol were found to stimulate oligodendrocyte differentiation in a high-throughput drug screening assay; thus, they may play a role in the risk reduction of multiple sclerosis (MS). So far, they have not been examined in any clinical data. This study aims at investigating the association between ipratropium and salmeterol and reduced diagnosis of MS with the use of real-world clinical data., Methods: We conducted a 1:10 matched case-control study that compared the exposure of ipratropium and salmeterol between patients with MS and control patients over the past 2 years, using the MS Flowsheet Registry of OSF HealthCare Saint Francis Medical Center. Cases were matched to control patients, based on service year/quarter, age, sex, race, and payer type. The relationship was examined with a Poisson regression model and a generalized structural equation model., Findings: The sample in our analysis included 217 patients with MS and 2164 matched control patients. The mean (SD) age for both patients with MS and control patients was 41 (11.8) years with a range of 18 to 75 years. The MS group had consistently less prescriptions of ipratropium and salmeterol than the control group in the past 1, 2, and 3 years before the index date. Our multivariable analysis found that the control group had 3.2 more prescriptions (95% CI, 1.4-7.1; P = 0.006) of either ipratropium or salmeterol in the past 2 years than the MS group, even if controlling for other confounders. In the generalized structural equation model, we found that use of ipratropium and salmeterol was significantly associated with reduced diagnosis of MS (P = 0.036), whereas smokers and people with family history of MS were more likely to have a diagnosis of MS (P < 0.001)., Implications: The observed association between ipratropium and salmeterol use and reduced diagnosis of MS indicates that they might potentially serve as agents in the treatment of MS., (Copyright © 2019. Published by Elsevier Inc.)

Background: Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described., Aim: To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV., Methods: A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total., Results: Both inhaled and lung doses were greater with VMN (22.78 ± 3.38% and 12.05 ± 2.96%, respectively) than JN (12.51 ± 6.31% and 3.14 ± 1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ± 1.3% versus 46.44 ± 5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN., Conclusions: VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis., Methods and Analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence., Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit., Ethics and Dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals., Trial Registration Number: NCT03738917; Pre-results., Competing Interests: Competing interests: AM and CL report receiving research grants from Abbott Diagnostics., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the findings, resulting changes in management, and safety profile of flexible bronchoscopy in the neonates with severe bronchopulmonary dysplasia., Study Design: This was a retrospective case series of twenty-seven neonates with severe bronchopulmonary dysplasia who underwent flexible bronchoscopy in the neonatal intensive care unit., Results: Flexible bronchoscopy revealed airway pathology in 20/27 (74%) patients. Tracheomalacia 13/27 (48%), bronchomalacia 11/27 (40.7%), and airway edema 13/27 (48%) were the most common findings. Bronchoalveolar lavage (BAL) was performed in 17 patients. BAL culture revealed a microorganism in 12/17 (70.5%) cases. Findings from bronchoscopy resulted in change in clinical management in 17/27 (63%) patients. Common interventions included initiation of antibiotics (37%) and treatment of tracheobronchomalacia with bethanechol (22.2%), atrovent (18.5%), and PEEP titration (18.5%). Bronchoscopy was performed without significant complication in 26/27 (97%) patients., Conclusion: Flexible bronchoscopy can be a safe and useful tool for the management of neonates with severe bronchopulmonary dysplasia.

Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

Background: Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development as a once-daily nebulized therapy for chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD., Methods: In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 μg), active control ipratropium (500 μg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion. In Study 0091, 59 patients were randomized to receive once-daily inhalations of revefenacin (22, 44, 88, 175, 350 or 700 μg) or placebo for 7 days in a double-blind, incomplete block, five-way crossover design. The primary efficacy endpoint was change from baseline in peak (0-6 h) forced expiratory volume in 1 s (FEV 1 ) in Study 0059, and trough FEV 1 after the final dose (Day 7) in Study 0091. In both studies, secondary endpoints included area under the FEV 1 -time curve (FEV 1 AUC) values from time 12-24 h post dose and FEV 1 AUC values from time zero to 24 h post dose., Results: Revefenacin demonstrated a rapid onset and sustained duration of bronchodilator action in both studies. In Study 0059, mean peak FEV 1 was significantly higher (p < 0.001) for revefenacin and ipratropium compared to placebo, with differences of 176.8 mL for 350 μg revefenacin, 162.2 mL for 700 μg revefenacin and 190.6 mL for ipratropium. In Study 0091, mean trough FEV 1 on Day 7 was significantly higher (p < 0.006) for all revefenacin doses compared to placebo, with differences ranging from 53.5 mL (22 μg dose) to 114.2 mL (175 μg dose). The results for the other spirometry endpoints were consistent with the primary endpoint for each study, demonstrating that the bronchodilator effect of revefenacin lasted more than 24 h following nebulized administration. Revefenacin was rapidly absorbed and extensively metabolized, followed by a slow apparent terminal elimination and minimal accumulation with repeated dosing. In both studies, adverse events were generally mild and occurred with similar frequencies in all groups, with no indication of significant systemic anti-muscarinic activity at any dose., Conclusions: Following single or multiple nebulized-dose administration in patients with COPD, revefenacin demonstrates a rapid onset and sustained duration of bronchodilator effect over 24 h following once-daily administration, with a PK profile that is commensurate with low systemic exposure., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: In addition to lung volume restriction, persons with chronic tetraplegia demonstrate obstructive airway physiology evinced by pharmacologically-induced bronchodilation. We previously found independent evidence that anticholinergic agents (ipratropium bromide; IB) and beta-2 adrenergic agonists (albuterol sulfate; AS) were associated with significant bronchodilation in subjects with tetraplegia as determined via spirometry or body plethysmography. Direct comparison of these two classes of agents has received little attention., Methods: Twelve subjects with chronic tetraplegia completed single dose treatment on alternate days with nebulized IB or AS. Patients underwent pre- and 30-minute post-bronchodilator spirometry, body plethysmography, and impulse oscillation system (IOS) in accordance with established protocols., Results: Spirometry and specific airway conductance revealed significant bronchodilator responsiveness following both IB and AS. As determined by increases in specific airway conductance post-bronchodilator, IB tended toward greater bronchodilation than AS (71% vs. 47%). IOS revealed a greater reduction in central airway resistance (R20) following IB compared to AS (22% vs. 9%, P < 0.01). A greater number of subjects exhibited a clinically significant reduction in R20 following IB compared to AS (58% vs. 8%, P < 0.01)., Conclusion: Among subjects with tetraplegia, both IB and AS elicit significant bronchodilation, although the magnitude of the bronchodilator response is greater following IB. This lends support to theory of overriding cholinergic airway tone in tetraplegia. The IOS findings further suggest that the predominant site of action of IB is upon the larger central airways congruent with findings in able-bodied subjects.

Objective: We investigated the effects of ventilator mask atomization inhalation of ipratropium bromide and budesonide suspension liquid in the treatment of acute exacerbation COPD (AECOPD) on circulating levels of inflammatory factors and prognosis., Patients and Methods: A total of 86 cases of patients on ventilator support were randomly divided into control group and observation group with 43 cases each. The control group was administered routine treatment including basic disease treatment, anti-infection, maintenance of a stable internal environment, nutritional support, oxygen inhalation and so on. The control group was administered saline through a ventilator mask. The observation group was treated with atomized inhalation of ipratropium bromide and budesonide suspension and oxygen flow 3-5 L/min, 15-20 min/time and twice a day for 1 week. The treatment effects were compared., Results: Serum TNF-α, IL-6, and CRP levels were decreased in both groups after treatment, but levels in the observation group were significantly lower than those of the control group; differences were statistically significant (p < 0.05). Forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/FVC and maximal expiratory flow rate in the observation group were significantly higher than those in the control group after treatment (p < 0.05). After treatment, the PaO2, SpO2 and respiratory failure index (RFI) of the observation group were significantly higher than those of the control group. The PaCO2 levels of the observation group were lower than those of the control group. The differences were statistically significant (p < 0.05). The clinical efficacy of the observation group was better than that of the control group; the ventilation time and total treatment time was significantly shorter and the differences were statistically significant (p < 0.05)., Conclusions: The ventilator mask atomizing inhalation of ipratropium bromide and budesonide suspension liquid in the treatment of AECOPD can significantly improve circulating inflammatory reaction, improve lung function and blood gas levels, increase the treatment efficiency, and shorten the treatment time.

Objectives: To evaluate the efficacy of brief, single administration of positive expiratory pressure (PEP) therapy in reducing clinical severity and need for additional second-line therapies and hospitalization in children presenting to the emergency department (ED) with acute asthma., Study Design: This was a prospective randomized controlled trial of children 2-18 years of age presenting to a tertiary-care academic pediatric ED with moderate-to-severe asthma exacerbations from December 2014 to June 2016. Children who continued to have moderate asthma severity after completion of initial therapies (albuterol/ipratropium bromide and corticosteroids) were randomized to receive PEP therapy or standard of care. The primary outcome was change in pulmonary asthma score before and after intervention, as assessed by a blinded physician. Secondary outcomes included need for additional therapies, ED length of stay, and disposition., Results: A total of 52 patients were randomized to receive either PEP (n?=?26) or standard therapy (n?=?26). Study groups were similar in demographics and baseline characteristics. There was no significant difference in primary outcome between groups with a mean change in Pulmonary Asthma Score of 0.92 (±1.2) in the PEP group and 0.40 (±1.2) in the standard group (P?=?.12). There also was no significant difference in need for additional therapies, ED length of stay, and disposition. Mild, self-resolving side effects were observed in 3 subjects receiving PEP therapy., Conclusion: Single, brief, administration of PEP therapy after completion of first-line therapies does not improve clinical severity in children presenting to the ED with acute asthma., Trial Registration: ClinicalTrials.gov: NCT02494076., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV 1 responses to ipratropium bromide., Methods: Data from the Lung Health Study (n=5887; 37% females) were used to determine changes in FEV 1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients., Results: After 4months, ipratropium therapy increased FEV 1 by 6.0% in female and 2.9% in male subjects from baseline values (p=2.42×10 -16 ). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV 1 with ipratropium were observed in thin female subjects (p for BMI∗sex interaction=0.044). The sex-related changes in FEV 1 related to ipratropium persisted for 2years (p=0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p=6.86×10 -8 )., Conclusion: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Inhaled short-acting anticholinergics (SAAC) and short-acting beta₂-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone., Objectives: To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma., Search Methods: We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies., Selection Criteria: Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria., Data Collection and Analysis: For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model., Main Results: We included 23 studies that involved a total of 2724 enrolled participants. Most studies were rated at unclear or high risk of bias.Overall, participants receiving combination inhaled therapy were less likely to be hospitalised (RR 0.72, 95% CI 0.59 to 0.87; participants = 2120; studies = 16; I² = 12%; moderate quality of evidence). An estimated 65 fewer patients per 1000 would require hospitalisation after receiving combination therapy (95% 30 to 95), compared to 231 per 1000 patients receiving SABA alone. Although combination inhaled therapy was more effective than SABA treatment alone in reducing hospitalisation in participants with severe asthma exacerbations, this was not found for participants with mild or moderate exacerbations (test for difference between subgroups P = 0.02).Participants receiving combination therapy were more likely to experience improved forced expiratory volume in one second (FEV₁) (MD 0.25 L, 95% CI 0.02 to 0.48; participants = 687; studies = 6; I² = 70%; low quality of evidence), peak expiratory flow (PEF) (MD 36.58 L/min, 95% CI 23.07 to 50.09; participants = 1056; studies = 12; I² = 25%; very low quality of evidence), increased percent change in PEF from baseline (MD 24.88, 95% CI 14.83 to 34.93; participants = 551; studies = 7; I² = 23%; moderate quality of evidence), and were less likely to return to the ED for additional care (RR 0.80, 95% CI 0.66 to 0.98; participants = 1180; studies = 5; I² = 0%; moderate quality of evidence) than participants receiving SABA alone.Participants receiving combination inhaled therapy were more likely to experience adverse events than those treated with SABA agents alone (OR 2.03, 95% CI 1.28 to 3.20; participants = 1392; studies = 11; I² = 14%; moderate quality of evidence). Among patients receiving combination therapy, 103 per 1000 were likely to report adverse events (95% 31 to 195 more) compared to 131 per 1000 patients receiving SABA alone., Authors' Conclusions: Overall, combination inhaled therapy with SAAC and SABA reduced hospitalisation and improved pulmonary function in adults presenting to the ED with acute asthma. In particular, combination inhaled therapy was more effective in preventing hospitalisation in adults with severe asthma exacerbations who are at increased risk of hospitalisation, compared to those with mild-moderate exacerbations, who were at a lower risk to be hospitalised. A single dose of combination therapy and multiple doses both showed reductions in the risk of hospitalisation among adults with acute asthma. However, adults receiving combination therapy were more likely to experience adverse events, such as tremor, agitation, and palpitations, compared to patients receiving SABA alone.

Background: Inhaled anticholinergics such as ipratropium bromide (IB), when administered with β2-agonists, are effective in reducing hospital admissions of children presenting to the emergency department with moderate to severe asthma. However, treatment of acute asthma with IB is still uncommon in Japan. The aim of this study was to investigate the effectiveness and safety of IB for the treatment of pediatric acute asthma., Methods: We conducted a retrospective study to compare the admission rate of patients who received IB with those who did not. Patients aged 4 years or older with a history of moderate to severe attacks were included. For analysis, propensity score matching was used to adjust the confounding factors related to IB use. Patients received IB by metered-dose inhaler (40μg per dose) with a spacer three times at 20-min intervals., Results: Among 175 patients included in the analysis, 102 patients were treated with IB (IB group) and 73 patients were treated without IB (Non-IB group). A propensity score matching analysis extracted 63 patients from each group. There was no statistical difference between the two groups in terms of admission rate (IB group 12.7% vs Non-IB group 9.5%; p=0.78). One patient (1.0%) treated with IB experienced dryness of the mouth, which resolved spontaneously., Conclusions: The admission rate did not decline with IB use. Several confounding factors could have influenced and limited our results. A prospective study is needed to investigate the effectiveness of IB in Japan.

Background: Asthma is the most common pediatric chronic disease and currently affects 7.1 million children in the United States. Many children experience acute asthma exacerbations. Many children also require hospitalization despite treatment in an emergency department with current standard therapy (corticosteroids, albuterol, and ipratropium). These hospitalizations may be avoided if effective adjunctive therapies can be developed to adequately treat severe exacerbations., Methods: Publications were searched in the PubMed database using the following keywords: magnesium AND asthma AND children AND randomized controlled trial. A total of 30 publications were returned. References of relevant articles were also screened. We included publications of controlled randomized trials where intravenous magnesium sulfate was studied in children (age < 18 years) with acute asthma (n = 7). We excluded studies in adults or trials with other formulations of magnesium (e.g., nebulized)., Results: Previous studies have demonstrated that intravenous magnesium sulfate (IV MgSO 4 ) significantly improves respiratory function and reduces hospitalization rate in children with moderate to severe asthma exacerbations. Current dosing regimens involve a short infusion of 25-75 mg/kg over 20 min (maximum 2-2.5 g/dose), though no studies have directly compared dosages for relative efficacy. Several studies suggest utilizing a peak plasma concentration of magnesium higher than 4 mg/dL as a surrogate of efficacy. This review summarizes the literature regarding the use of IV MgSO 4 for the treatment of pediatric acute asthma., Conclusions: We suggest that optimized dosing regimens could be developed using a linked pharmacokinetic-pharmacodynamic modeling and simulation approach. We propose the factors that should be considered in future clinical trial design in order to better understand the use of IV MgSO 4 in pediatric acute asthma. Pediatr Pulmonol. 2016;51:1414-1421. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations. Severe disease may progress to chronic respiratory failure. We reviewed the literature on basic medications available for COPD, using the standard Prescrire methodology. There are few clinical data on treatment of mild COPD. Regular medication is not necessary for patients who do not have recurrent symptoms. Eliminating exposure to cigarette smoke and other irritants such as workplace irritants, is the only measure known to improve the outcome of COPD. Evaluation of inhaled short-acting beta-2 agonists is based mainly on short-term trials. These drugs have been shown to improve dyspnoea. Salmeterol and formoterol, two long-acting beta-2 agonists, have been extensively evaluated in symptomatic patients. Compared with no treatment, these drugs reduce breathlessness and acute exacerbations, preventing about two hospital admissions per 100 patients with moderate to severe COPD treated for 7 months. Indacaterol and olodateroldo not have a better harm-benefit balance. Inhaled beta-2 agonists occasionally provoke cardiovascular disorders. No excess mortality has been reported among the thousands of COPD patients included in clinical trials. There Is little evidence that ipratropium, an inhaled short-acting anti-muscarinic bronchodilator, improves COPD symptoms. A risk of Increased mortality among COPD patients treated with ipratroplum cannot be ruled out. Tiotroplum, an inhaled long-acting antimuscarinic bronchodilator, has been extensively evaluated In COPD. Tiotroplum has symptomatic efficacy in COPD, reducing dyspnoea and acute exacerbations. Tiotroplum had no tangible advantages over long-acting beta-2 agonists in seven randomised trials including more than 12 000 patients. Glycopyrronium and aclidinium, two other Inhaled long-acting antimuscarinics, do not appear to be more effective. Tiotroplum, like other inhaled anti-muscarinics, has antimuscarinic adverse effects including cardiac, visual and buccal disorders. Glycopyronium may carry a higher risk of serious cardiovascular effects. Combination of an antimuscarinic with an inhaled beta-2 agonist improves symptoms in 7% to 10% of patients. In patients with one or two COPD exacerbations per year, adding an Inhaled corticosterold (beclometa- sone, budesonide or fluticasone) to a long-acting beta-2 agonist prevents about 1 exacerbation during 3 to 4 years of treatment. Inhaled corticosteroids can cause pneumonia, candidiasis, dysphonia and adrenal Insufficiency. Fluticasone seems to have more adverse effects than other inhaled corticosterolds. Theophylline has uncertain efficacy on symptoms of COPD. This drug has a narrow therapeutic index and carries a risk of serious adverse effects. It should not be used in COPD. Long-term treatment with roflumilast or oral corticosteroids has an unfavourable harm-benefit balance in COPD. In practice, in 2016, the first measure in COPD is to eliminate exposure to the irritant, most often tobacco. Drugs used in COPD have only modest, mainly symptomatic efficacy. Treatment should be adapted to symptoms and the frequency of exacerbations: a short-acting beta-2 agonist should be tried first, then replaced by an inhaled long-acting bronchodilator, or possibly tiotropium, when its effect is too short-lived. An inhaled corticosteroid can be added if symptoms persist or exacerbations are frequent.

This study aimed to investigate the role of M3 acetylcholine receptor (M3-AChR) expression in airway remodeling. Additionally, we aimed to evaluate the effects of ipratropium bromide solution inhaled in an early phase of asthma on airway remodeling in ovalbumin (OVA)-sensitized and challenged mice. Thirty BALB/c mice were divided into three groups, namely, control group (saline sensitized/challenged mice), asthma group (OVA sensitized/challenged mice), and treatment group (OVA sensitized/challenged mice treated by ipratropium bromide). Pathological changes were detected by histological staining in the bronchopulmonary tissue of mice. WAt/Pbm (the airway wall area /basement membrane perimeter) ratio of the asthma group (25.37 ± 4.25) increased significantly (P < 0.05) when compared with that of the control (12.89 ± 1.71) and treatment group (15.82 ± 2.91). WAm/Pbm (smooth muscle wall area / basement membrane perimeter) ratio of the asthma group (7.58 ± 2.16) increased significantly (P < 0.05) when compared with that of the control (2.55 ± 0.72) and treatment group (3.36 ± 1.69). M3-AChR concentration increased in the treatment group (29.24 ± 3.59) and was significantly different (P < 0.05) from that of the control group (25.50 ± 1.83). During asthma treatment, SAMA can alleviate airway remodeling in murine model by lessening the thickness of bronchial walls and inhibiting the proliferation of smooth muscle cells. There were no obvious changes in M3-AChR density in the murine model of asthma characterized by airway remodeling. However, ipratropium bromide may up-regulate the expression of M3-AChR in bronchial walls of asthmatic murine model.

Objective: To compare the efficacy of nebulised salbutamol alone and in combination with ipratropium bromide in acute severe asthma in children., Methods: The randomised controlled trial was conducted at the National Institute of Child Health, Karachi, from October 2012 to March 2013, and comprised patients with acute severe asthma who were randomised into two equal groups. Group A patients received 3 doses of nebulised salbutamol alone (0.03 ml/kg/dose) at 15-minute intervals and Group B received 3 similar doses of salbutamol along with ipratropium (250 ug/dose). Acute severe asthma was categorised as serve exacerbation (clinical score >10) and moderate (5-10 score) based on Bentur Modification. Efficacy was measured after 5minutes of the last dose by change in severity score from severe exacerbation (baseline) to low score. SPSS 10 was used for statistical analysis., Results: There were two groups of 100(50%) patients each. The mean age in Group A was 9.1±3 years and 9.3±2.8 years in Group B. Male-Female ratio in Group A was 1.5:1 and in Group B it was 1.2:1. In Group B, 93(93%) children showed improvement in clinical score (<10 score) while it was 84(84%) in Group A. There was better response in clinical score in Group A than Group B, but it was not significant (p>0.05)., Conclusions: The combination of nebulised salbutamol along with ipratropium bromide in the treatment of acute asthma exacerbation was not superior to salbutamol alone.