Inhalation Of Formoterol Research Articles

Influence of Leukotriene Pathway Polymorphism on Responsiveness to Montelukast, Budesonide Plus Formoterol in Patients with Asthma

Variability between patients in response to montelukast, and budesonide / formoterol inhalation powder may be related to genetic variation and non-genetic factors. this paper aims to determine association between polymorphism in leukotriene pathway candidate gene with lung function outcomes in Iraqi patients with asthma receiving montelukast, budesonide plus formoterol inhaler in comparison with healthy control. This research was done on a study group of 80 Baghdad-based Iraqi patients. 40 asthmatic patients receiving montelukast were in the first group, while 40 asthmatic patients on budesonide / formoterol inhalation powder (160/4.5mcg/dose) were in the second group. Screening for the presence of ALOX5 rs2115819, LTA4H rs2660845 and CysLTR1 rs320995 SNPs allelic variants genes were determined using conventional PCR technique and sequencing. In montelukast group, the % change in FEV1 in patients with the GG genotype for ALOX5 (rs2115819) SNP were significantly improved after montelukast intake compared with those carrying AA or AG genotypes. For budesonide / formoterol inhalation powder patients group, the included polymorphism had no significant association with the %change in FEV1. As a conclusion Asthmatic patients carrying AA genotype for ALOX5 rs2115819 may not achieved the optimal response to montelukast treatment. Budesonide / formoterol inhalation powder cannot be used effectively in patients with ALOX5 rs2115819 polymorphism.

Clinical Efficacy Analysis of Tiotropium Bromide Combined with Budesonide and Formoterol Inhalation in Treating COPD

Objective: To analyze the clinical efficacy of tiotropium bromide (TB) combined with budesonide formoterol (BUD/FM) inhalation in treating chronic obstructive pulmonary disease (COPD). Methods: 62 COPD patients admitted to the hospital between June 2020 and December 2022 were selected as samples for this study. The patients were divided into a combination group and a conventional group using the random number table method, with 31 cases in each group. The patients in the combination group were treated with TB combined with BUD/FM inhalation, whereas the patients in the conventional group were treated with BUD/FM inhalation only. The treatment efficacy and changes in lung function indicators of both groups were compared. Results: The total efficacy of treatment in the combined group was higher than that in the conventional group, and the difference was statistically significant (P < 0.05). Before treatment, there was no difference in pulmonary function indicators between the two groups (P > 0.05). After three months of treatment, all lung function indicators of the combined group were higher than those of the conventional group, and the difference was statistically significant (P < 0.05). Conclusion: Combining TB with BUD/FM inhalation therapy increases the efficacy of treatment for patients with COPD. Besides, it also improves lung function and leads to a better prognosis.

Efficacy of Budesonide and Formoterol Inhalation Aerosol in Conjunction with Doxofylline in Chronic Obstructive Pulmonary Disease

Efficacy of Budesonide and Formoterol Inhalation Aerosol in Conjunction with Doxofylline in Chronic Obstructive Pulmonary Disease

Effects of Combined Inhalation of Budesonide, Formoterol, and Tiotropium Bromide on Arterial Blood Gas and Pulmonary Function Indexes in Patients with Chronic Obstructive Pulmonary Disease

Objective: To analyze the effect of combined inhalation of budesonide formoterol and tiotropium bromideon arterial blood gas and pulmonary function indexes in patients with chronic obstructive pulmonary disease (COPD). Methods: 100 patients with COPD treated from January to December 2022 were selected as observation objects, and were divided into a control group (n = 50, in which budesonide and formoterol were administered) and an experimental group (n = 50, the treatment drug was budesonide formoterol combined with tiotropium bromide) according to the computer grouping method, and compared the treatment results. Results: (i) Before treatment, there was no difference in the partial pressure of carbon dioxide and partial pressure of oxygen between the control group and the experimental group (P > 0.05); after treatment, the partial pressure of carbon dioxide and partial pressure of oxygen in the experimental group were higher than those in the control group, with significant differences (P < 0.05). (ii) Before treatment, there was no difference in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC between the control group and the experimental group (P > 0.05); after treatment, the FVC, FEV1, and FEV1 /FVC in the experimental group weresignificantly higher than those in the control group (P < 0.05). (iii) There was no difference in the levels of CRP, IL-6, and TNF-α between the control group and the experimental group (P > 0.05); after treatment, the levels of CRP, IL-6, and TNF-α in the experimental group were lower than those in the control group, with significant differences (P <0.05). (iv) Compared to the total incidence of adverse reactions in the control group (28.00%), the incidence of total adverse reactions in the experimental group was lower at 10.00%, and the difference was significant (P < 0.05). Conclusion: The combined inhalation of budesonide and formoterol with tiotropium bromide has demonstrated a clear therapeutic efficacy and safety in treating chronic obstructive pulmonary disease. This treatment approach effectively enhances arterial blood gas levels and lung function, showing promising potential for widespread application.

Assessing prescriber adherence with Global Initiative for Asthma (GINA) guideline-recommended reliever therapy.

In 2019, a landmark change was made to the Global Initiative for Asthma (GINA) guidelines in which an as-needed low-dose inhaled corticosteroid (ICS)-formoterol inhaler was updated to be the preferred reliever therapy for all asthma patients. Use of short-acting beta-agonist monotherapy is no longer recommended. The purpose of this study was to assess provider adherence with the GINA guidelines in regards to reliever therapy. This was a retrospective cohort study of patients presenting with an acute asthma exacerbation from January to May of 2020 and 2021. The primary objective of this study was to quantify provider adherence with the GINA guidelines in terms of reliever therapy. Preferred reliever therapy was defined asuse of an as-needed low-dose ICS-formoterol combination inhaler. Alternative reliever therapy was defined as use of a SABA inhaler with ICS-containing controller therapy. Secondary objectives included the number of patients discharged on any form of corticosteroid and the number of patients who may have been ideal candidates for transition to preferred reliever therapy. A total of 127 patients were included in the analyses. Upon hospital discharge, three patients (2.4%) received preferred reliever therapy and 97 (76.4%) received alternative reliever therapy. Rates of recommended reliever therapy prescription increased from 55 to 79% upon hospital discharge (p < 0.001). Prescription of GINA guideline-recommended reliever therapy was 79% within the patient population evaluated; however, rates significantly improved following hospitalization for asthma exacerbation. Additional studies that assess barriers to guideline adherence may be recommended.

A148 CASE REPORT: ASSOCIATION OF HOUSE DUST MITE ALLERGY AND REMISSION OF EOSINOPHILIC ESOPHAGITIS AFTER ELIMINATION OF SHRIMP

Abstract Background Eosinophilic esophagitis (EoE) is a complex, chronic, allergic disease that commonly presents as dysphagia in young adults. Co-occurring allergic or atopic disease, including food allergies and asthma are seen in approximately 70% of cases. Allergy to house dust mite (HDM) tropomyosin, Der p 10, and cross-reactivity to shrimp has been well described. We discuss a presentation of EoE in the setting of positive HDM skin prick testing that subsequently improved with dietary elimination of shrimp, that has never been described in the literature. Purpose To highlight an underlying mechanism in EoE and the importance of a multidisciplinary approach to this disease. Method A 45-year-old male with a medical history significant for ulcerative colitis (diagnosed two years prior and maintained in deep endoscopic remission with adalimumab) and asthma (with seasonal, rare usage of budesonide and formoterol inhaler) was seen by his outpatient gastroenterologist following three weeks of new-onset dysphagia and subjective intermittent food bolus impaction. The patient was pre-emptively started on daily proton pump inhibitor prior to endoscopy, but discontinued this within less than two weeks as he felt like it induced loose bowel movements. Esophagogastroduodenoscopy (EGD) was performed and revealed proximal esophageal furrows. Histology of esophageal biopsies was compatible with EoE: distal esophagus &amp;gt;100 eosinophils/hpf with eosinophil degranulation, mid and proximal esophagus &amp;gt;25 eosinophils/hpf with eosinophil degranulation. The patient self-identified that his episodes of dysphagia and food bolus impaction were associated with shrimp ingestion, thus he eliminated shrimp from his diet. Result(s) Two-month clinical follow-up demonstrated symptomatic remission despite no other active treatment or additional food elimination. Consultation with an allergist demonstrated the patient had positive skin prick testing to HDM (Dermatophagoides pteronyssinus and farina) but negative testing to shrimp, despite clinical improvement with dietary shrimp elimination. Thus his EoE was attributed to HDM cross-reactivity, specifically to the Der p 10 antigen. Follow-up EGD and biopsy to confirm endoscopic and histologic remission with shrimp elimination is scheduled in two months. Conclusion(s) This is the first case description of a patient with new onset EoE attributed to Der p 10, in the setting of positive skin prick to HDM and negative skin prick to shrimp, with subsequent symptomatic resolution of EoE following dietary shrimp elimination. Shrimp and HDM share a protein, Der p 10. Der p 10 is commonly the culprit antigen in patients that have allergic reactions to HDM and (or) shrimp, but often only demonstrate positive skin prick testing to HDM (with negative testing to shrimp). This case demonstrates a role for involvement of an allergist and skin prick testing in select cases of EoE, as this may result in a relatively simple food elimination and avoidance of further therapeutic interventions. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Simultaneous microdetermination of different penicillin antibiotics residues for cross-contamination study in non-penicillin dosage forms

Cross-contamination of non-penicillin products with penicillin drugs can initiate life-threatening allergic hypersensitivity reactions, thus, all non-penicillin products should be tested for contamination before sale. This work describes a fast simple HPLC-DAD method for the simultaneous microdetermination of nine penicillin drugs for studying cross contamination of non-penicillin pharmaceutical dosage forms. Separation was done on C18 column with elution using 0.02 M phosphate buffer and methanol delivered in gradient mode and detection at 220 nm using DAD. Separation of all penicillins from non-penicillin drugs and their co-formulated excipients (methyl paraben, propyl paraben, sorbitol and sodium benzoate) with acceptable suitability parameters was obtained. The linearity ranges were within the range of 0.5–100 µg·mL−1 with good accuracy (Er% between −0.24 and 0.21 %) and precision (RSD% between 0.47 and 0.71 %). Good sensitivity was indicated by the obtained low limits of detection (0.1–1 µg·mL−1) for all the studied compounds. Successful application of the developed method in studying cross contamination of different non-penicillin products including salbutamol syrup and respiratory solution, miconazole cream, biperiden tablet, formoterol inhaler capsule and omeprazole capsule with residues of 9 penicillin drugs was performed without interference from all adjuvants. Henceforth, the proposed method can be recommended for the routine quality control to study and determine cross contamination of the non-penicillin facility with trace amounts of any of the studied penicillins with high accuracy and precision.

Comparative efficacy of leukotriene modifier and inhaled corticosteroids in the complex treatment of steroid-naive patients with bronchial asthma combined with chronic obstructive pulmonary disease with neutrophilic type of inflammation

The aim: to compare the efficacy and tolerability of the leukotriene modifier and inhaled corticosteroids in combination with long-acting β2-agonist formoterol in steroid-naive patients with asthma combined with COPD with neutrophilic inflammation. Materials and methods. After obtaining the written consent, 30 patients with asthma combined with COPD and a number of blood neutrophils &gt;4000/μl were randomized (1:1): group I – received a fixed combination of budesonide/formoterol 160/4.5 μg/1 inhalation twice daily as a basic therapy; group II – montelukast 1 tab. (10 mg) once daily and inhalation of formoterol 12 mcg/dose twice daily. The duration of therapy was 12 weeks. General clinical methods, asthma control questionnaires, COPD questionnaire, physical tolerance evaluation (6-minute walk test), pulmonary function tests, quality of life assessment were performed to all the patients before and after the treatment course studied. Results. The combination of budesonide/formoterol improved clinical symptoms – significantly (P &lt; 0.05) increased the total ACT score, decreased the average ACQ score, shortness of breath (mMRC scale), COPD symptoms. PFT indices were improved significantly (P &lt; 0.05), bronchoobstruction at the level of large, medium and small bronchi was significantly reduced. Physical tolerance was significantly improved. There were no statistically significant dynamics of the studied indices in patient group II. The patients of both groups showed a tendency to improve their quality of life. In patients of I group, there was a significant decrease in activity limitations and the total SGRQ score. Conclusions. The combination of inhaled corticosteroid/formoterol has proven to be more effective than the leukotriene modifier or formoterol in steroid-naive patients with asthma combined with COPD and neutrophilic inflammation.

"OLD IS THE NEW NORMAL"

Dear Reader, “Every cloud has a silver lining”. A few “side effects” of the Covid era are welcome for diverse reasons. The “webinars explosion” on the internet and the new normal experience of “work from home” and online operations have produced “travel-saving”, “time-saving” and “overhead saving” economics in corporate and academic environs. More particularly, the new “innovation culture” that has emerged in the small-medium pharma sector as the response to the patient needs in the pandemic tsunami is a welcome development. In the wake of this repurposing spree, many “grandfather” drugs have found renewed interest. The revival of HCQ has been relatively short-lived compared to the “evergreen” Paracetamol which is being dispensed both to Covid patients in early stages and post vaccination to one and all. The medical profession as well as clinical researchers have taken to these proven remedies with low but well known (often nil) side effects. There are many examples. Recent research was shown that “Budesonide” inhaler (and the Budesonide and Formoterol inhalation) is an effective prophylactic as well as early stage Covid-19 therapy.

A study on symptom improvement and efϑicacy of formoterol plus budesonide in the asthma management in northern parts of Tamil Nadu

The purpose is to study the asthma symptom improvement and efficacy of formoterol (LABA) and Budesonide (ICS) combination in the asthma management in northern districts of Tamilnadu. It is a multicentric, non-comparative, questionnaire and random sampling study was conducted in 145 mild to severe asthmatic patients. They were in Formoterol plus budesonide combination inhalation drugs available in DPI and pMDI. Among the 145 asthmatic patients, 45 patients, 6 patients and 94 patients were in DPI, nebuliser and pMDI devices respectively. During drug initiation, The Asthmatics were in mild (27%), Moderate (57%) and Severe (16%) stages. After one year of follow-up, the number of patients in the mild is 84%, moderate 14% and severe 2%. Among 45 DPI Asthmatic patients, 29 patients, 15 patients and 1 patient have reported the handling the devices as easy, medium and hard respectively. On the other hand, 94 pMDI asthmatic patients, 38 patients, 48 patients and 8 patients have reported the handling of devices as easy, medium and hard respectively. The treatment resulted in 77 patients as good, 65 as satisfactory and 3 as same. After one year, all the 145 asthmatic patients adhered with the treatment and experienced symptom improvement with 53% patients as good, 45% patients as satisfactory and 2% patients as same. The treatment of formoterol and budesonide combination in the northern districts of Tamilnadu have effectively controlled the asthmatic symptoms and improved the quality of life in asthmatics. Moreover, the patient's adherence to the treatment is good in the northern parts of Tamilnadu.

Evaluating the Clinical Outcomes of Three Medication Regimens for Treating a Sample of Iraqi Persistent Asthmatic patients

Abstract&#x0D; Asthma is a complex disease defined by chronic airway inflammation and airflow limitation causing variable respiratory symptoms which include shortness of breath (SOB), wheezing, chest tightness and cough. Asthma guidelines advocate adding a second long acting bronchodilator to medium doses of inhaled corticosteroids (ICS) rather using high doses of ICS alone to control moderate to severe persistent asthma. The aim of this study was to evaluate the clinical outcomes of three medication regimens indicated for Iraqi patients suffering from persistent asthma. &#x0D; This study was interventional randomized clinical study conducted on a sample of adult Iraqi asthmatic patients in Baghdad City. The study composed of three visits distributed over eight weeks; baseline visit followed by first follow up and second follow up visits after four and eight weeks respectively. The study enrolled 78 adult patients with moderate to severe persistent asthma as diagnosed by specialist physician according to patient history and baseline pulmonary function test (PFT) and allocated them randomly to three groups (each group included 26 patients) to receive equivalent medium doses of budesonide inhaler in addition to either formoterol inhaler, oral modified release aminophylline tablets or tiotropium inhaler (first, second and third group respectively). Sixty four patients completed this study. The mean ages of patients were above 35 years with slightly more male predominance.&#x0D; The study groups developed significant increase of peak expiratory flow rate (PEFR) and forced vital capacity (FVC) values at the first follow up visit compared to baseline values (p&lt;0.001). Thereafter, the first and third groups achieved significant higher values at the second follow up visit compared to first follow up visit (p&lt;0.001), while second group produced no change. All the groups developed significant improvement of Mini asthma quality of life questionnaire (MiniAQLQ) scores and percentage of symptom free days (SFD) at first follow up visit and continued further significant improvement at the second follow up visit (p&lt;0.001). Generally, between groups comparison according to extent of change of study parameters revealed that third group produced the greatest improvement over the entire study period followed by the first group, whereas the second group was associated with the least extent of improvement.&#x0D; This study concluded that all groups caused significant improvement in study parameters compared to baseline values and also concluded that the third group of inhaled [tiotropium/budesonide] was associated with the highest extent of improvement followed by first group, while the second group was the least. &#x0D;

Improved Sprint Performance With Inhaled Long-Acting β2-Agonists Combined With Resistance Exercise.

To investigate the impact of twice-daily inhalation of 100µg of salmeterol (SAL) or 12µg of formoterol (FOR) in addition to a strength- and power-training program over a 5-wk period on a 30-m sprint, strength, power, mood, stress, and skinfold thickness. In a randomized, single-blind study, 23 male and 15 female nonasthmatic, recreationally active individuals were recruited (mean [SD] age 26.3 [5.4]y, weight 76.2 [11.5]kg, height 176.9 [8.5]cm). Participants completed 3 standardized whole-body strength- and power-training sessions per week for 5wk during which they were assigned to an SAL, FOR, or placebo group. Participants used their inhaler twice per day as instructed and completed assessments of sprint, strength, and power at baseline and 1wk after cessation of the training program. The assessments included a 30-m sprint, vertical jump, 1-repetition-maximum (1RM) bench press, 1RM leg press, peak torque flexion and extension, anthropometric evaluation, and Rest-Q questionnaires. After 5 wk of strength and power training, 30-m sprint time reduced in the FOR (0.29 [0.11]s, P = .049) and SAL (0.35 [0.05]s, P = .040) groups compared with placebo (+0.01 [0.11]s). No significant change was found in other assessments of strength, mood, or skinfold thickness. When strength and power training are combined with the inhalation of FOR or SAL over a 5-wk period, moderately trained individuals experience an improvement in 30-m sprint performance.

The response variability of the asthma patients to the standard pharmacotherapy

Background. The aim of this study was to analyse the group of patients with asthma, who prefer to use short-acting anticholinergics (SAMA) for relief of asthma attacks. At the same time, these patients are prescribed inhaled glucocorticosteroids (ICS) in combination with long-acting P2-agonists (LABA) as a basic therapy according to the standards. Tha aim. To study the cause of low efficacy of LABA in patients with asthma who do not have a sufficient response to SABA, as well as the probability of reducing of bronchial obstruction with LAMA. Materials and methods. 12 non-smoking adults with moderate to severe asthma (III-IV stage of GINA), receiving medium or high doses of ICS in combination with LABA as a basic therapy without adequate control over asthma symptoms were included in the study. First group of patients showed the efficacy of salbutamol (FEV1 reversibility was more than 12% and more than 200 ml after 400 ^g of salbutamol) and ipratropium bromide (SABA+SAMA+). Second group included patients with low response to salbutamol and positive test (FEVt reversibility) with ipratropium bromide (SABA-SAMA+). Spirometry was performed at baseline point and in 5, 10, 15, 30, 60, 120 and 240 min after inhalation of bronchodilator (salmeterol 50 ^g, formoterol 12 ^g and tiotropium bromide 18 ^g in the different days). Results. It was shown that SABA-SAMA+ phenotype asthma patients demonstrated low response to LABA: FEV1 increased up to 7.64±1.67%, 156.0±16.0 ml after salmeterol inhalation and up to 9.4±5.8%, 166.7±103.1 ml after formoterol inhalation (compared with a group of SABA+SAMA+, where the response to salmeterol was 20.81±2.42%, 551.43±93.94 ml and the response to formoterol was 30.21±6.75%, 718.57±140.78 ml, p

Enantioselective disposition of (R,R)-formoterol, (S,S)-formoterol and their respective glucuronides in urine following single inhaled dosing and application to doping control.

Formoterol is a long-acting beta2-adrenoceptor agonist (LABA) used for the treatment of asthma and exercise-induced bronchoconstriction. Formoterol is usually administered as a racemic (rac-) mixture of (R,R)- and (S,S)-enantiomers. While formoterol is restricted by the World Anti-Doping Agency (WADA), inhalation of formoterol is permitted to a predetermined dose (54μg/24hours) and a urine threshold of 40ng/mL. However, chiral switch enantiopure (R,R)-formoterol is available, effectively doubling the therapeutic advantage for the same threshold. The aim of this study was to investigate whether formoterol exhibits enantioselective urinary pharmacokinetics following inhalation. Six healthy volunteers were administered a 12μg inhaled dose of rac-formoterol. Urine was collected over 24 hours and analyzed by enantioselective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. Total (free drug plus conjugated metabolite) median (min-max) rac-formoterol urine levels following inhalation were 1.96 (1.05-13.4) ng/mL, 1.67 (0.16-9.67) ng/mL, 0.45 (0.16-1.51) ng/mL, 0.61 (0.33-0.78) ng/mL, and 0.17 (0.08-1.06) ng/mL at 2, 4, 8, 12, and 24hours, respectively, well below the 2019 urine threshold. The proportion of conjugation differed between enantiomers with glucuronide conjugation much greater for (R,R)-formoterol (around 30%-60% of total) compared to (S,S)-formoterol (0%-30%). There was clear evidence of inter-individual enantioselectivity observed in the ratios of (R,R):(S,S)-formoterol, where (S,S)- was predominant in free formoterol, and (R,R)- predominant in the conjugated metabolite. In conclusion, rac-formoterol delivered by inhalation exhibits enantioselective elimination in urine following single-dose administration. Enantioselective assays should be employed in doping control to screen for banned beta2-agonist chiral switch products such as (R,R)-formoterol, and total hydrolyzed rac-formoterol is warranted to account for inter-individual differences in enantioselective glucuronidation.

Beta2 -adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses.

While studies have demonstrated substantial differences in beta2 -adrenergic agonist enantiomer pharmacology, enantioselective disposition of long-acting beta2 -adrenergic ligand racemic (rac)-formoterol in blood is inadequately explored after inhaled therapy given analytical challenges. Furthermore, information on enantioselective disposition and partitioning of beta2 -adrenergic agonist in skeletal muscle is absent despite its promising data on muscle anabolism in humans. Using a sensitive ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay, we determined disposition of (R,R)-formoterol and (S,S)-formoterol in plasma and skeletal muscle samples from 11 non-asthmatic men who had inhaled rac-formoterol at therapeutic doses (2×27μg). Mean (SD) concentrations of (R,R)- and (S,S)-formoterol in plasma and in muscle biopsies of the vastus lateralis 1hour after inhalation of formoterol were 31 (15) and 45 (18) pg×mL-1 for (R,R)-formoterol and (S,S)-formoterol, respectively, in plasma, and 0.56 (0.32) and 0.51 (0.29) pg×mgwet wt -1 , respectively, in muscle. Formoterol exhibited different enantioselective disposition in plasma and muscle (p<0.0001). In plasma, mean log (R,R):(S,S)-formoterol ratio was lower than 0 [-0.17(0.07), p<0.0001], whereas in muscle, mean log (R,R):(S,S)-formoterol ratio was slightly higher than 0 [0.04(0.07), p<0.05]. Log (R,R):(S,S)-formoterol ratio in muscle was related to muscle fiber-type composition. Furthermore, formoterol induced an approximately two-fold increase in muscle p-PKASer/thr phosphorylation (p<0.01), indicating a substantial beta2 -adrenergic response. Collectively, these findings suggest that formoterol exhibits modest enantioselective disposition in plasma after inhaled therapy in humans, which appear related to a greater (R,R)-enantiomer disposition in skeletal muscle that may be dependent on fiber-type composition.

Suicide Attempt by Swallowing with 60 Formoterol Inhaler Capsules: A Case Report

Suicide Attempt by Swallowing with 60 Formoterol Inhaler Capsules: A Case Report

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting.

Comparison of the effectiveness and safety of formoterol versus salmeterol in the treatment of patients with asthma: A systematic review and meta-analysis.

Formoterol and salmeterol are two long-acting β2-agonists given by inhalation, with bronchodilating effects lasting for at least 12 h after a single administration. Formoterol has a faster onset of action compared with salmeterol. The aim of this study was to perform a systematic review and meta-analysis on the data published from previous review in order to calculate pooled estimates of effectiveness and safety assessment of formoterol and salmeterol in treatment of patients with asthma. In this study, we conducted an electronic search for medical citation databases including Cochrane, PubMed, Scopus, PsycInfo, and IranMedex. Besides manual search of the databases that record randomized clinical trials, conference proceedings, and journals related to asthma were included. Studies were evaluated by two independent people based on inclusion and exclusion criteria, and the common outcomes of studies were entered into the RevMan 5.0.1 software, after evaluation of studies and extraction of data from them; and in cases where there were homogeneous studies, meta-analysis was performed, and for heterogeneous studies, the results were reported qualitatively. Of the 1539 studies initially found, 13 were included in the study. According to the meta-analysis conducted, no significant difference was found between the inhalation of formoterol 12 μg and salmeterol 50 μg in the two outcomes of mean forced expiratory volume 1 s (FEV1), 12 h after inhalation of medication and Borg score (A frequently used scale for quantifying breathlessness) after inhalation of medication. In addition, salmeterol was more effective than formoterol in the two outcomes of percent decrease in FEV1 after inhalation of methacholine and the number of days without an attack. Since the two outcomes of FEV1 30-60 min after inhalation of medication and morning peak expiratory flow after inhalation of medication were heterogeneous, they had no meta-analysis capabilities, and its results were reported qualitatively. The data from included studies shows that, more efficacy has been achieved with Salmeterol, especially in some outcomes such as the percent decrease in FEV1 after inhalation of Methacholine, and the number of days without an attack; and therefore, the administration of Salmeterol seems to be beneficial for patients, compared with Formoterol.

Efficacy and safety of maintenance and reliever combination budesonide–formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial

The Single combination budesonide-formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients, but whether the high doses of corticosteroid and β agonist increase the risk of adverse effects with both short-term and cumulative exposure is not certain. Our aim was to investigate whether the SMART regimen would reduce the risk of overuse of β agonist, reduce the likelihood of patients to seek medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid. In this 24-week trial undertaken at four primary health-care practices and one hospital in New Zealand, patients (aged 16-65 years) with a recent asthma exacerbation were randomly assigned in a 1:1 ratio to the SMART or standard fixed-dose regimen. Treatment in the SMART group consisted of two actuations of budesonide-formoterol (200 μg and 6 μg, respectively, per actuation) twice daily, delivered through a combination metered dose inhaler (MDI), with one extra actuation as needed for relief of symptoms; treatment in the standard group consisted of two actuations of budesonide-formoterol (200 μg and 6 μg, respectively, per actuation) twice daily through a combination MDI with one to two actuations of salbutamol (100 μg per actuation) by MDI as needed for relief of symptoms. MDIs were monitored electronically to measure actual use of medication. The allocation sequence for randomisation was computer generated, with a block size of eight per site. Participants, investigators, and the statistician were not masked to group assignment. The primary outcome was the proportion of participants with at least one high-use episode of β agonist (more than eight actuations per day of budesonide-formoterol in addition to the four maintenance doses in the SMART group or more than 16 actuations per day of salbutamol in the standard group). Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000515099. 303 patients were randomly assigned to the SMART (n=151) or standard group (n=152). No significant difference was noted between the SMART and standard groups in the proportion of participants with at least one high-use episode of β agonist (84 [56%] vs 68 [45%], respectively, relative risk 1·24 [95% CI 0·99-1·56]; p=0·058). There were fewer days of high use in the SMART group (mean 5·1 days [SD 14·3] vs 8·9 days [20·9], relative rate 0·58 [0·39-0·88]; p=0·01). Of the patients who had at least one high-use episode, those in the SMART group had fewer days of high use without medical review (8·5 days [17·8] vs 18·3 days [24·8], 0·49 [0·31-0·75]; p=0·001). The SMART regimen resulted in higher inhaled corticosteroid exposure (943·5 μg budesonide per day [1502·5] vs 684·3 μg budesonide per day [390·5], respectively; ratio of means 1·22 [1·06-1·41]; p=0·006), but reduced oral corticosteroid exposure (77·5 mg prednisone [240·5] vs 126·6 mg prednisone [382·1], respectively; p=0·011), with no significant difference in composite systemic corticosteroid exposure (793·7 mg prednisone equivalent per year [893·1] vs 772·1 mg prednisone equivalent per year [1062·7], respectively; 1·03 [0·86-1·22]; p=0·76). Participants in the SMART group had fewer severe asthma exacerbations (35 [weighted mean rate per year 0·53] vs 66 [0·97]; relative rate 0·54 [0·36-0·82]; p=0·004). The SMART regimen has a favourable risk-to-benefit profile and can be recommended for use in adults at risk of severe asthma exacerbations. Health Research Council of New Zealand.

A Case of Ropinirole-Induced Compulsive Behavior

To the Editor: Parkinson’s disease is a neuropsychiatric condition. Dopamine agonists are used extensively in the treatment of Parkinson’s. A retrospective review in 2009 of patients with Parkinson’s disease reported a frequency of 13.2% for compulsive behavior including new-onset pathological gambling and hypersexuality after being started on therapeutic doses of pramipexole or ropinirole.1 Several reports and reviews have been published on this topic. Here we present a case of new-onset compulsive behavior with the dopamine agonist ropinirole in a patient who presented in a mental health clinic setting. Case report. Mr A, a 41-year-old white, married male veteran with a history of Parkinson’s disease with cognitive impairment as well as DSM-IV-TR posttraumatic stress disorder and major depressive disorder, single episode, moderate, was referred to the mental health clinic by his primary care physician for management of his psychiatric symptoms. The patient reported that his depressive symptoms had been stable since he started treatment with venlafaxine 2 months earlier, but for the past few months he was having compulsive behavior, including intense sexual desires toward other women, and had started to gamble on scratchcards, on which he had lost $1,000 to $1,500 in a month. This was unusual for him, as he had a supportive and loving wife and had never gambled before. He had noted an increase in appetite (weight gain of 20 lb [9.1 kg]), endorsed that he had compulsive eating behaviors, and drank about a 20-pack of beer per day. He also described having nightmares and vivid dreams and endorsed having visual hallucinations in the form of shadows in the room on multiple occasions. This behavior had been causing stress in his marriage. He had no previous history of strokes, seizures, bipolar disorder, psychosis, impulse-control disorder, or drug dependence. His psychiatric medications included venlafaxine 150 mg twice daily, zolpidem 10 mg at bedtime, and clonazepam 1 mg twice daily, and his Parkinson’s disease medications included tablet carbidopa/levodopa 25 mg/250 mg every 3 hours, ropinirole 3 mg 3 times daily, entacapone 200 mg every 5 hours, and donepezil 10 mg at bedtime. Other medications were tramadol, losartan, flunisolide nasal inhaler, albuterol metered-dose inhaler, cetirizine, formoterol inhaler, and mometasone metered-dose inhaler. Mr A informed us that, at his last visit, his neurologist had increased his ropinirole dosage from 1 mg orally twice daily to 3 mg orally twice daily, as he was experiencing dyskinesia, swallowing difficulty, gradual decline in memory, and worsening of his Parkinson’s symptoms. Review of medical records confirmed that he indeed started having this weight gain and impulsive behavior within the first few weeks after the ropinirole dose was increased. After conducting a literature search on ropinirole, we decided to discontinue the medication. Following discontinuation, the symptoms resolved completely, and Mr A started to have weight loss and did not have the urge to gamble; however, his Parkinson’s motor symptoms reemerged. Thus, he was restarted on ropinirole at 0.5 mg orally twice daily for 1 wk and then increased to 1 mg orally twice daily, which he tolerated well without reemergence of his symptoms. The appearance of symptoms on increasing the dose and then improvement with reducing the dose suggests a strong correlation between ropinirole and impulsive behavior. This case highlights the importance of awareness regarding drug-related psychiatric symptoms that may originate in the course of management of Parkinson’s disease. Physicians who care for patients taking dopamine agonists should watch for and differentiate between conditions including drug-induced adverse effects from primary psychiatric disorders and work in collaboration with neurologists to manage these treatment-emergent adverse effects.