Ipratropium Bromide Treatment Research Articles

Cholinergic neuron-like D-U87 cells promote polarization of allergic rhinitis T-helper 2 cells.

Parasympathetic nerve hypersensitivity contributes to the severity of allergic rhinitis (AR), but the precise mechanism underlying neuroimmune regulation in patients with AR remains unclear. This study investigated the effect of cholinergic nerve inhibition on AR CD4+ T-helper (Th)2-cell polarization and the underlying regulatory mechanism in vitro. An in-vitro neuroimmune coculture model of D-U87 cells and CD4+ T cells was established. D-U87 cells with cholinergic neuron characteristics were used as cholinergic neuron models. CD4+ T cells were derived from peripheral blood monocytes from AR patients (n = 60) and control subjects (n = 40). Th1- and Th2-cell percentages were measured by flow cytometry. Proteins involved in related signaling pathways were analyzed by protein chip assay and Western blotting. The Th2-cell percentage among CD4+ T cells from AR patients was significantly increased after coculture with D-U87 cells and was decreased by ipratropium bromide (IB) treatment. In contrast, the Th1-cell percentage among control CD4+ T cells was significantly increased after coculture with D-U87 cells, but was unaltered by IB treatment. Furthermore, phosphorylated Akt (p-Akt) protein levels increased in CD4+ T cells from both controls and AR patients after coculture with D-U87 cells and decreased after IB treatment. However, higher p-Akt levels were observed in cells from AR patients than in cells from control subjects. Moreover, Akt inhibition decreased Th2-cell percentage in AR patients. In-vitro cholinergic nerve inhibition with IB decreased AR CD4+ T-cell polarization into Th2 cells partially through an Akt-dependent mechanism.

IPRATROPIUM BROMIDE NEBULIZER-ASSOCIATED ANISOCORIA

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Anisocoria, is a rare clinical sign with a long list of differential diagnoses. It is often treated as a form of intracranial pathology until proven otherwise. However, if a patient lacks additional ocular abnormalities or neurological deficits, it is less likely that this clinical sign is due to intracranial pathology. Here, we present a patient with COPD exacerbation who developed anisocoria after inhaled ipratropium bromide treatment. CASE PRESENTATION: 71-year-old female was admitted to the intensive care unit for acute hypoxic respiratory failure due to a COPD exacerbation and pneumonia. The patient was intubated and started on broad spectrum antibiotics. She was later extubated to BiPAP and subsequently transferred to the general medical floor. While on BiPAP, she was receiving nebulized Ipratropium bromide/albuterol sulfate every 4 hours. Shortly after starting one of her nebulizer treatments, the rapid response team was called to evaluate to the patient for a new onset fixed and dilated left pupil. She did not have any other neurological deficits and a CT head was negative for acute intracranial pathology. After further evaluation, the BiPAP face mask was found to have a faulty seal. Patient was given a new face mask with minimal leaks, and the mydriasis resolved within 12 hours. DISCUSSION: Anisocoria is a clinical sign that can warrant concern. Rare but life-threatening diagnoses include uncal herniation, intracranial hemorrhage/mass or posterior-communicating artery aneurysm, that each impair adjacent parasympathetic innervation leading to unopposed sympathetic innervation of the iris. Consequently, this clinical sign is often treated as intracranial pathology until proven otherwise. However, in the absence of other ocular abnormalities or neurological deficits, it is unlikely that this clinical sign is due to intracranial pathology. Pharmacological causes should initially be considered. Ocular anticholinergics that cause temporary mydriasis include atropine, scopolamine, hyoscyamine, and often mis-directed aerosolized ipratropium bromide. In our patient, the mydriasis was a result of nebulized ipratropium with unintentional contact the eye by an improperly fitted nebulizer mask. The use of the pilocarpine eye drop test can help confirm a pharmacological muscarinic blockade if pilocarpine has no miotic effect. Additionally, the subsequent resolution of anisocoria 2-48 hours after discontinuation of nebulized anticholinergic is further support. An alternative diagnosis should be pursued if the pilocarpine test causes miosis, if the mydriasis becomes fixed and persistent, or if there are additional ocular or neurological abnormalities. CONCLUSIONS: With the widespread use of nebulized treatments, it is essential to be aware of this sign as it is important to consider these reversible causes as a potential diagnosis that guides subsequent management. Reference #1: Chaudhry P, Friedman DI, Yu W. Unilateral pupillary mydriasis from nebulized ipratropium bromide: A false sign of brain herniation in the intensive care unit. Indian J Crit Care Med. 2014;18(3):176-7. Reference #2: Yalcin S, Pampal K, Erden A, Oba S, Bilgin S. Do we really need to panic in all anisocoria cases in critical care?. Indian J Anaesth. 2010;54(4):365-6. Reference #3: Yalcin S, Pampal K, Erden A, Oba S, Bilgin S. Do we really need to panic in all anisocoria cases in critical care?. Indian J Anaesth. 2010;54(4):365-6. DISCLOSURES: No relevant relationships by Mirza Ali, source=Web Response No relevant relationships by M Bakir, source=Web Response No relevant relationships by SarahGrace Carbrey, source=Web Response No relevant relationships by Abdisamad Ibrahim, source=Web Response No relevant relationships by Thamer Sartawi, source=Web Response

Effects of anticholinergic agent on miRNA profiles and transcriptomes in a murine model of allergic rhinitis.

Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis. The expression levels of candidate genes were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The data indicates that the symptoms scores in allergic mice were significantly reduced by IB treatment. In the nasal mucosa of allergic mice with IB treatment, 207 mRNAs and 87 miRNAs were differentially expressed, when compared with the sham group. IB treatment significantly downregulated the expression levels of interleukin-4Rα and prostaglandin D2 synthase, whereas the leukemia inhibitory factor, A20 and nuclear receptor subfamily 4, group A, member 1 expression levels were upregulated. Similarly, the expression levels of mmu-miR-124-3p/5p, −133b-5p, −133a-3p/5p, −384-3p, −181a-5p, −378a-5p and −3071-5p were significantly increased. RT-qPCR data further validated these mRNA and miRNA expression levels. Thus, IB treatment regulated expression of allergic immune-associated mRNAs and miRNAs of the nasal mucosa in allergic mice, which may be associated with ameliorated nasal allergic symptoms.

Changes of T-helper type 1/2 cell balance by anticholinergic treatment in allergic mice

BackgroundAnticholinergic drugs or vidian neurectomy can alleviate the symptoms of allergic rhinitis. ObjectiveTo show that inhibition of the cholinergic nerve influences the balance of T-helper type 1 and 2 cells in allergic rhinitis mice. MethodsTwenty-four mice were randomly allocated to 1 of 4 groups: control, model, model with ipratropium bromide treatment, and model with 6-hydroxydopamine treatment. Allergic model-treated mice were sensitized with ovalbumin. Evaluation of allergic symptoms was recorded according to a symptom score. Ovalbumin serum IgE was measured by enzyme-linked immunosorbent assay. Expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptides was detected by immunohistochemistry and imaging analysis. ResultsSymptoms in allergic mice were significantly alleviated by ipratropium bromide. Ovalbumin serum IgE and eosinophils of nasal mucosa were significantly decreased. Interleukin-4 expression level was significantly higher in the allergic model group than in the control group and significantly decreased by ipratropium bromide (P < .05). In contrast, the expression of forkhead box P3 was lower in the allergic model group than in the control group and increased with treatment by ipratropium bromide (P < .05). Conversely, interferon-γ expression was not changed by anticholinergic treatment in the nasal mucosa of allergic mice. Expression of substance P and vasoactive intestinal peptide was significantly increased in allergic mice and decreased by ipratropium bromide. Sympathetic denervation did not change the expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptide. Conclusioninhibition of the cholinergic nerve not only alleviated symptoms of allergic rhinitis by inhibiting the impulse of the parasympathetic nerve but also modulated the T-helper type 2–predominant immune reaction, expression of neuropeptides, and related inflammation factors.

Stimulation of Suicidal Erythrocyte Death by Ipratropium Bromide

Background/Aims: Ipratropium bromide, an anticholinergic agent widely used in obstructive lung disease, has previously been shown to trigger suicidal death of nucleated cells or apoptosis. Despite their lack of mitochondria and nuclei, key organelles in the execution of apoptosis, erythrocytes may similarly undergo suicidal cell death, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). The present study explored whether ipratropium bromide triggers eryptosis. Methods: [Ca Ca²⁺]_i was estimated utilizing Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from annexin-V-binding, and hemolysis from hemoglobin release. Results: A 48 h exposure to ipratropium bromide (1 nM) significantly increased [Ca²⁺]_i, decreased forward scatter and increased annexin-V-binding. Ipratropium bromide treatment was followed by slight but significant increase of hemolysis. Removal of extracellular Ca²⁺ or inhibition of Ca²⁺ permeable cation channels with amiloride (1 mM) virtually abolished cell membrane scrambling. Ca²⁺ ionophore ionomycin (1 µM, 30 min) increased the percentage of phosphatidylserine exposing erythrocytes to similarly high levels in the absence and presence of ipratropium bromide (1 nM). Conclusions: Ipratropium bromide triggers suicidal erythrocyte death or eryptosis, an effect mainly due to stimulation of Ca²⁺-entry.

Bronchodilators in Bronchoscopy-Induced Airflow Limitation in Allergen-Sensitized Cats

This study investigated the effect of bronchoscopy and bronchoalveolar lavage (BAL) on respiratory function, determined by barometric whole-body plethysmography (BWBP), of healthy and allergen-sensitized cats. Furthermore, the efficacy of inhaled bronchodilators in preventing changes in respiratory function was determined. For test 1, 18 healthy experimental cats were investigated on day 1 by BWBP. On day 2, the cats underwent BWBP after sedation (medetomidine), after anesthesia induction (propofol), and after bronchoscopy and BAL. Enhanced pause (Penh) was significantly increased after bronchoscopy and BAL (1.64 ± 0.17 versus 1.23 ± 0.07, P < .05). For test 2, 6 cats were sensitized to ovalbumin (OVA), 6 cats were sensitized to Ascaris suum (AS), and 6 cats served as controls. On day 0, OVA- and AS-sensitized cats underwent an inhaled allergen challenge, whereas controls were exposed to saline. On days 1 and 2, the same protocol as described for test 1 was repeated. Post-BAL Penh of the AS-sensitized cats was significantly higher than at test 1 (2.28 ± 0.22 versus 1.69 ± 0.33, P < .05) and was correlated with BAL fluid neutrophil count (r= 0.55, P < .05). During tests 3, 4, and 5, the same protocol as used for test 2 was applied to each cat group, with the animals being randomly treated before sedation with inhaled salbutamol (200 μg), ipratropium bromide (40 μg), or a combination of both (200 + 40 μg). Post-BAL Penh of the AS-sensitized group was significantly decreased after the salbutamol + ipratropium bromide treatment (1.56 ± 0.18 versus 2.28 ± 0.22, P < .05). This study suggests that bronchoscopy and BAL induce airflow limitation in cats, which is more severe in the presence of lower airway inflammation. Inhaled salbutamol + ipratropium bromide reduce BAL-induced bronchoconstriction in AS-challenged cats and might be recommended as preventive treatment of asthmatic cats undergoing bronchoscopy.

Bronchodilators in Bronchoscopy-Induced Airflow Limitation in Allergen-Sensitized Cats

This study investigated the effect of bronchoscopy and bronchoalveolar lavage (BAL) on respiratory function, determined by barometric whole-body plethysmography (BWBP), of healthy and allergen-sensitized cats. Furthermore, the efficacy of inhaled bronchodilators in preventing changes in respiratory function was determined. For test 1, 18 healthy experimental cats were investigated on day 1 by BWBP. On day 2, the cats underwent BWBP after sedation (medetomidine), after anesthesia induction (propofol), and after bronchoscopy and BAL. Enhanced pause (Penh) was significantly increased after bronchoscopy and BAL (1.64 +/- 0.17 versus 1.23 +/- 0.07, P < .05). For test 2, 6 cats were sensitized to ovalbumin (OVA), 6 cats were sensitized to Ascaris suum (AS), and 6 cats served as controls. On day 0, OVA- and AS-sensitized cats underwent an inhaled allergen challenge, whereas controls were exposed to saline. On days 1 and 2, the same protocol as described for test 1 was repeated. Post-BAL Penh of the AS-sensitized cats was significantly higher than at test 1 (2.28 +/- 0.22 versus 1.69 +/- 0.33, P < .05) and was correlated with BAL fluid neutrophil count (r = 0.55, P < .05). During tests 3, 4, and 5, the same protocol as used for test 2 was applied to each cat group, with the animals being randomly treated before sedation with inhaled salbutamol (200 microg), ipratropium bromide (40 microg), or a combination of both (200 + 40 microg). Post-BAL Penh of the AS-sensitized group was significantly decreased after the salbutamol + ipratropium bromide treatment (1.56 +/- 0.18 versus 2.28 +/- 0.22, P < .05). This study suggests that bronchoscopy and BAL induce airflow limitation in cats, which is more severe in the presence of lower airway inflammation. Inhaled salbutamol + ipratropium bromide reduce BAL-induced bronchoconstriction in AS-challenged cats and might be recommended as preventive treatment of asthmatic cats undergoing bronchoscopy.

Paralytic Ileus Possibly Associated with Nebulized Ipratropium Bromide

Objective: To report a case of paralytic ileus possibly associated with nebulized ipratropium bromide. Case Summary: A 43-year-old man fell from a wall and was admitted to the intensive care unit (ICU) for the resulting thoracic trauma. An epidural thoracic catheter was placed for pain control using bupivacaine 0.25% and methadone 0.2 mg/mL. On hospital day 4, he developed purulent bronchiole constriction, and treatment with nebulized mesna and ipratropium bromide was started. Six hours after the first nebulization, the patient developed abdominal pain and bowel distension. An abdominal X-ray showed intestinal gas retention and dilated loops of large bowel. Paralytic ileus was diagnosed. Nebulized ipratropium bromide treatment was stopped and, during the following 24 hours, the patient gradually improved. Discussion: Nebulized ipratropium bromide–induced paralytic ileus is an uncommon adverse event that may be of considerable clinical relevance. Nebulized ipratropium bromide is predominantly deposited in the oropharynx, but some amount of the drug may be swallowed with resultant systemic adverse effects. Ipratropium bromide is a nonselective muscarinic antagonist and may inhibit contraction of the gastrointestinal tract. Paralytic ileus could not be attributed to an electrolyte disturbance or abdominal injury. The patient's paralytic ileus resolved when nebulized ipratropium bromide was stopped. An objective causality assessment showed that the paralytic ileus was possibly associated with this drug. Conclusions: This case report indicates that ipratropium bromide should be considered capable of inducing paralytic ileus.

In Patients With COPD, Treatment With a Combination of Formoterol and Ipratropium Is More Effective Than a Combination of Salbutamol and Ipratropium: A 3-Week, Randomized, Double-Blind, Within-Patient, Multicenter Study

To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. A randomized, double-blind, double-dummy, two-period, crossover clinical trial. Twenty-four clinics and university medical centers in nine countries. One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.

Effect of Ipratropium Bromide Treatment on Oxygen Saturation and Sleep Quality in COPD

Patients with COPD are at risk of experiencing a deterioration in arterial oxygen saturation (SaO2) during sleep, which is generally most pronounced during rapid eye movement (REM) sleep. Increased cholinergic tone has been suggested as a contributing factor to this decrease in SaO2. Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD. Randomized, placebo-controlled, double-blind, two-arm parallel study of 4 weeks of treatment with ipratropium bromide solution or placebo. Multicenter investigation. Thirty-six patients with moderate-to-severe COPD (FEV1 < 65% of predicted). Evaluation included polysomnographic, pulmonary function, and subjective quality of sleep (visual analog scale [VAS]) assessments. It was found that 4 week of treatment with ipratropium bromide solution in patients with COPD led to the following: (1) a significant (p = 0.05) improvement in mean nocturnal SaO2 with the more severe the nocturnal desaturation, the greater the improvement in SaO2; (2) significant (p = 0.03) improvement in perceived sleep quality (VAS: 5.5 +/- 0.5 after placebo; 7.2 +/- 0.5 after ipratropium); (3) a significant (p = 0.05) increase in REM sleep time (48.6 +/- 6.3 min after placebo; 66.5 +/- 6.4 min after ipratropium) with no effect on other sleep stages or total sleep time; and (4) a significant (p = 0.01) increase in pre-sleep FVC and flow rate at 50% of the vital capacity. These findings demonstrate that ipratropium bromide therapy can improve sleep SaO2 as well as sleep quality in patients with moderate-to-severe COPD.

Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: A study of its effect on their symptoms, quality of life, and nasal cytology

Ipratropium bromide is an anticholinergic agent with topical activity that has been studied as a freon-propelled aerosol spray for therapy of nonallergic rhinitis. This is the first report of its use both as an aqueous nasal spray and in perennial allergic rhinitis. In this study 123 patients who had symptoms of perennial allergic rhinitis were randomized to receive ipratropium bromide 21 μg or 42 μg or placebo, one spray per nostril three times a day for 4 weeks. Patients maintained daily diaries of duration and severity of nasal symptoms and were evaluated weekly. Mean duration and severity of rhinorrhea was decreased in both ipratropium bromide treatment groups by comparison with placebo, with consistently greatest improvement in the group treated with ipratropium bromide 42 μg per nostril three times a day. No statistically significant differences occurred among treatment groups in duration or severity of postnasal drip, congestion, or sneezing. Seventy percent of patients treated with 42 μg of ipratropium bromide thought it had good or excellent effect on rhinorrhea ( p < 0.05 vs placebo); significantly more patients thought that it had improved the quality of life ( p = 0.02). No changes occurred in nasal cytology, and no significant local or systemic adverse events occurred. These data indicate that ipratropium bromide significantly decreases the rhinorrhea of perennial allergic rhinitis.

Tolerance to ß2-Agonists in Patients with Chronic Obstructive Pulmonary Disease

Eleven patients with severe COPD were examined to determine whether tolerance to beta 2-agonists developed after long-term inhalation therapy with these agents. Before the study all patients were on regular treatment with inhaled salbutamol for six months. At the beginning of the study, response of FEV1 to inhaled salbutamol was measured. Dose-response curves were measured after three weeks of treatment with ipratropium bromide and again after a three-week course of inhaled salbutamol. After ipratropium bromide treatment, responses to low doses of salbutamol tended to be larger than after salbutamol treatment, but differences were not significant. Three hours after the last inhalation of salbutamol the FEV1 was lower on days 1 and 42 than on day 21. We conclude that long-term inhalation therapy with beta 2-agonists in patients with COPD decreases the duration of the bronchodilation produced by the same agents but does not affect the peak response.

Effect of four weeks' high dose ipratropium bromide treatment on lung mucociliary clearance.

In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.