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Expert Opinion on Pharmacotherapy Jan 2012Airway hyperresponsiveness (AHR) is a key feature of asthma and can be assessed by the use of bronchial provocation tests. A test using inhaled dry powder mannitol for... (Review)
Review
INTRODUCTION
Airway hyperresponsiveness (AHR) is a key feature of asthma and can be assessed by the use of bronchial provocation tests. A test using inhaled dry powder mannitol for diagnosing asthma is now regulatory approved in 20 countries.
AREAS COVERED
This paper reviews the literature on inhaled mannitol from the first publication in 1997 until present (October 2011). It discusses the current knowledge on the clinical usefulness as a tool for diagnosing and managing asthma.
EXPERT OPINION
Inhaled mannitol can be regarded as a safe, standardized, specific, but less sensitive, tool for the diagnosis of asthma in both children and adults. Discomfort, in terms of cough, during the test occurs in 85.3% of subjects, but rarely (1.3%) leads to discontinuation. Headache (6.1%), pharyngolaryngeal pain (2.6%) and cough (1.3%) are the most frequent adverse events that occur on the day of the test. The test holds several advantages compared with existing tests; there is no need for additional equipment (i.e., a nebulizer) besides a spirometer; it requires no cleaning and has only one standard operating protocol. In a new study using mannitol for monitoring mild and moderate persistent asthma in primary care, the number of mild exacerbations was reduced.
Topics: Administration, Inhalation; Asthma; Bronchial Provocation Tests; Humans; Mannitol
PubMed: 22118547
DOI: 10.1517/14656566.2012.638917 -
The Journal of International Medical... 2011Postoperative pharyngolaryngeal complications (PPLC) occur during anaesthesia due to increased cuff pressure following the insertion of laryngeal mask airways. The use... (Randomized Controlled Trial)
Randomized Controlled Trial
Postoperative pharyngolaryngeal complications (PPLC) occur during anaesthesia due to increased cuff pressure following the insertion of laryngeal mask airways. The use of a pressure regulator to prevent PPLC was evaluated in a prospective, randomized study. Sixty patients scheduled to receive general anaesthesia were randomly assigned to two equal groups of 30, either with or without the regulator. The 'just seal' cuff pressure (JSCP), cuff pressure at 5-min intervals during anaesthesia, incidence of pharyngeal sore throat (PST), dysphagia, dysphonia and other complications were evaluated at 1 and 24 h postoperatively. The combined mean ± SD JSCP of both groups was 20.3 ± 3.2 mmHg. In the group with the regulator, cuff pressure was maintained at a constant level during anaesthesia. This study demonstrated that the regulator is a simple, functional device that can reduce the incidence of PST significantly at 1 h postoperatively, following general anaesthesia.
Topics: Adult; Aged; Anesthesia, General; Deglutition Disorders; Dysphonia; Female; Humans; Laryngeal Masks; Male; Middle Aged; Pharyngitis; Postoperative Period; Pressure; Treatment Outcome
PubMed: 22117992
DOI: 10.1177/147323001103900534 -
The Journal of Heart and Lung... Dec 2011Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study open-label extension.
BACKGROUND
Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy.
METHODS
A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH.
RESULTS
Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 ± 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double-blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]).
CONCLUSIONS
Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months.
Topics: Administration, Inhalation; Adolescent; Adult; Aged; Antihypertensive Agents; Blood Pressure; Bosentan; Double-Blind Method; Drug Therapy, Combination; Epoprostenol; Female; Headache; Humans; Hypertension, Pulmonary; Incidence; Longitudinal Studies; Male; Middle Aged; Nausea; Physical Endurance; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Young Adult
PubMed: 22055098
DOI: 10.1016/j.healun.2011.08.019 -
American Journal of Respiratory and... Nov 2011Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils.
OBJECTIVES
To evaluate the effect of the antibody to IL-5, reslizumab, in patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid.
METHODS
Patients were randomly assigned to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The primary efficacy measure was the difference between the reslizumab and placebo groups in the change in ACQ score from baseline to end of therapy (Week 15 or early withdrawal).
MEASUREMENTS AND MAIN RESULTS
Mean changes from baseline to end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P = 0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0 and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent of patients in the reslizumab group and 19% of patients in the placebo group had an asthma exacerbation (P = 0.083). The most common adverse events with reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain.
CONCLUSIONS
Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.
Topics: Adult; Antibodies, Monoclonal, Humanized; Asthma; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Interleukin-5; Leukocyte Count; Male; Middle Aged; Pulmonary Eosinophilia; Sputum; Surveys and Questionnaires; Treatment Outcome
PubMed: 21852542
DOI: 10.1164/rccm.201103-0396OC -
Allergy and Asthma Proceedings 2010The safety of loratadine (second-generation antihistamine) and montelukast (leukotriene receptor antagonist) as monotherapies is well documented. Safety of the...
The safety of loratadine (second-generation antihistamine) and montelukast (leukotriene receptor antagonist) as monotherapies is well documented. Safety of the fixed-dose, single-tablet therapy loratadine/montelukast (L/M; SCH 445761, containing loratadine [10 mg]/montelukast [10 mg]), for treatment of the symptoms of allergic rhinitis in >3800 subjects is described. Safety data from 19 randomized clinical studies in which subjects were administered L/M are presented. Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom, or laboratory data, including onset of new illness and exacerbation of preexisting conditions. Only AEs with an onset during the treatment period (i.e., treatment emergent) are summarized. Safety was also assessed via clinical laboratory evaluations and monitoring of vital signs and electrocardiogram (ECG). Overall, the incidence of AEs reported with L/M in the 19 studies was low and comparable with placebo, loratadine monotherapy, and montelukast monotherapy. The most frequently reported AE across all studies was headache. Most AEs were not severe and the duration of such events was short lived. Three AEs (headache [4.5%], fatigue [1.2%], and pharyngolaryngeal pain [1.2%]), regardless of relation to treatment, were reported by >1% of subjects in the L/M treatment group of multiple-dose, placebo-controlled studies. There were no clinically significant changes in clinical laboratory analyses or in vital signs, physical findings, or ECG found to be clinically relevant. Administration of the fixed-dose, single-tablet formulation of L/M was well tolerated. In these clinical studies, the safety of L/M was comparable with placebo, loratadine, and montelukast.
Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Clinical Protocols; Cyclopropanes; Disease Progression; Drug Combinations; Electrocardiography; Female; Headache; Humans; Loratadine; Male; Middle Aged; Quinolines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides
PubMed: 21708061
DOI: 10.2500/aap.2010.31.3401 -
The European Respiratory Journal Nov 2011This international phase III study of inhaled dry powder mannitol was a randomised, double-blind, 26-week study, followed by a further 26-week, open-label (OL)... (Randomized Controlled Trial)
Randomized Controlled Trial
This international phase III study of inhaled dry powder mannitol was a randomised, double-blind, 26-week study, followed by a further 26-week, open-label (OL) extension. 324 cystic fibrosis (CF) patients were randomised, in a 3:2 ratio, to mannitol (400 mg b.i.d.) and control groups. The primary efficacy end-point was to determine the change in forced expiratory volume in 1 s (FEV₁) over the double-blind phase. Secondary end-points included changes in forced vital capacity and pulmonary exacerbations. A significant improvement in FEV₁ was seen over 26 weeks (p<0.001) and was apparent by 6 weeks, irrespective of concomitant recombinant human deoxyribonuclease (rhDNase) use. At 26 weeks, there was a significant improvement in FEV₁ of 92.9 mL for subjects receiving mannitol compared with controls (change from baseline 118.9 mL (6.5%) versus 26.0 mL (2.4%); p<0.001). Improvements in FEV₁ were maintained up to 52 weeks in the OL part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045). The incidence of adverse events (AEs) was similar in both groups, although treatment-related AEs were higher in the mannitol compared with the control group. The most common mannitol-related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol showed sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.
Topics: Administration, Inhalation; Adolescent; Child; Cystic Fibrosis; Deoxyribonucleases; Double-Blind Method; Dry Powder Inhalers; Female; Forced Expiratory Volume; Humans; Male; Mannitol; Recombinant Proteins; Vital Capacity
PubMed: 21478216
DOI: 10.1183/09031936.00187510 -
Allergy and Asthma Proceedings 2011Nasal congestion is a frequent, bothersome symptom of seasonal allergic rhinitis (SAR). Mometasone furoate nasal spray (MFNS) has established efficacy in treating nasal... (Randomized Controlled Trial)
Randomized Controlled Trial
Nasal congestion is a frequent, bothersome symptom of seasonal allergic rhinitis (SAR). Mometasone furoate nasal spray (MFNS) has established efficacy in treating nasal allergy symptoms, but no study has been conducted with the primary purpose of evaluating MFNS for relief of congestion. This study assessed MFNS for congestion and other nasal symptoms in SAR. Two double-blind, placebo-controlled studies randomized symptomatic SAR patients to 15 days of MFNS, 200 micrograms, or placebo q.d. each morning. Participants scored individual components of total nasal symptom score (TNSS; congestion, rhinorrhea, sneezing, and itching) on a 4-point scale in the morning (A.M.) and evening (P.M.). Symptoms were scored for the time of assessment (NOW) and for the previous 12 hours (PRIOR). The pooled population comprised 684 patients randomized to MFNS (n = 344) or placebo (n = 340). Change from baseline in A.M./P.M. PRIOR nasal congestion score averaged over days 1-15, the primary end point, was significantly (p < 0.001) greater with MFNS than with placebo (0.68-point [25.2%] reduction versus 0.45-point [16.0%] reduction, respectively). Reduction in A.M./P.M. PRIOR TNSS averaged over days 1-15, a key secondary end point, was also superior with MFNS (2.83 points [28.5%] versus 1.79 points [17.6%]; p < 0.001). Predose A.M. NOW congestion, other nasal symptoms, and TNSS improved significantly more with MFNS, indicating 24-hour efficacy. Adverse events were infrequent and localized; the most common (epistaxis and pharyngolaryngeal pain) occurred in 1.0% of MFNS patients. MFNS q.d. provides sustained relief for nasal congestion and other SAR symptoms.
Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Obstruction; Nasal Sprays; Placebos; Pregnadienediols; Pruritus; Research Design; Rhinitis, Allergic, Seasonal; Sneezing; Treatment Outcome
PubMed: 21439168
DOI: 10.2500/aap.2011.32.3424 -
Indian Journal of Anaesthesia Aug 2009Supraglottic devices have changed the face of the airway management. These devices have contributed in a big way in airway management especially, in the difficult airway...
Supraglottic devices have changed the face of the airway management. These devices have contributed in a big way in airway management especially, in the difficult airway scenario significantly decreasing the pharyngolaryngeal morbidity. There is a plethora of these devices, which has been well matched by their wider acceptance in clinical practice. ProSeal laryngeal mask airway (PLMA) is one such frequently used device employed for spontaneous as well as controlled ventilation. However, the use of PLMA at times maybe associated with certain problems. Some of the problems related with its use are unique while others are akin to the classic laryngeal mask airway (cLMA). However, expertise is needed for its safe and judicious use, correct placement, recognition and management of its various malpositions and complications. The present article describes the tests employed for proper confirmation of placement to assess the ventilatory and the drain tube functions of the mask, diagnosis of various malpositions and the management of these aspects. All these areas have been highlighted under the heading of troubleshooting PLMA. Many problems can be solved by proper patient and procedure selection, maintaining adequate depth of anaesthesia, diagnosis and management of malpositions. Proper fixation of the device and monitoring cuff pressure intraoperatively may bring down the incidence of airway morbidity.
PubMed: 20640203
DOI: No ID Found -
Clinical Therapeutics Oct 2009Ticlopidine is an antiplatelet agent used for the prevention of vascular accidents. In clinical practice in Korea, ginkgo extract may be administered along with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticlopidine 250 mg/ginkgo extract 80 mg, and concomitant administration of ticlopidine 250-mg and ginkgo extract 80-mg tablets: an open-label, two-treatment, single-dose,...
BACKGROUND
Ticlopidine is an antiplatelet agent used for the prevention of vascular accidents. In clinical practice in Korea, ginkgo extract may be administered along with ticlopidine to enhance the inhibition of platelet aggregation.
OBJECTIVE
To meet the requirements for marketing a combined fixed-dose formulation in Korea, the investigators compared the pharmacokinetic characteristics of ticlopidine in a combined fixed-dose tablet of ticlopidine/ginkgo extract with the concomitant administration of ticlopidine and ginkgo extract tablets.
METHODS
An open-label, 2-period, 2-treatment, single-dose, randomized-sequence crossover study was conducted in healthy Korean male volunteers. Subjects were randomly allocated to 2 sequence groups. In one period, a combined ticlopidine 250 mg/ ginkgo extract 80-mg fixed-dose tablet was administered and, in the other period, ticlopidine 250-mg and ginkgo extract 80-mg tablets were concomitantly administered. A 7-day washout separated the 2 periods. For analysis of pharmacokinetic properties, including C(max), T(max), t((1/2)), AUC(0-infinity), and AUC(0-last), serial blood sampling was performed up to 48 hours after study drug administration during each period. Ticlopidine concentrations in plasma were determined by a validated method using LC-MS/MS. In order for the 2 treatments to be considered bioequivalent, the 90% CI of the geometric means ratios for C(max) and AUC needed to be between 80% and 125%. Bleeding time was determined before dosing (0 hour) and at 5 and 24 hours after dosing. Adverse events (AEs) were identified through patient interview, recording of blood pressure, heart rate, and body temperature, physical examination, 12-lead ECG, and laboratory assessments.
RESULTS
Twenty-four healthy Korean male subjects (mean [range] age, 23.9 [22-38] years; height, 174.0 [162-184] cm; weight, 67.4 [56-80] kg) completed the study. Median (range) T(max) of ticlopidine was 1.5 (0.5-2.0) hours in both groups. The mean (SD) t((1/2)) of ticlopidine in the combined fixed-dose formulation and the concomitant administration groups was 19.5 (3.4) and 19.0 (3.3) hours after study drug administration, respectively. The geometric means ratios of ticlopidine AUC(0-last), AUC(0-infinity), and C(max) between the combined fixed-dose formulation and concomitant administration were 1.04 (90% CI, 0.96-1.13), 1.04 (90% CI, 0.96-1.13), and 1.09 (90% CI, 0.96-1.23), respectively. The mean (SD) bleeding time at predose (0), and 5 and 24 hours after dose administration was 4.5 (1.6) to 5.4 (1.7) minutes in the combined fixed-dose formulation group and 4.4 (1.6) to 5.1 (1.1) minutes in the concomitant administration group. Five subjects (3 in the combined fixed-dose formulation group and 2 in the concomitant administration group) had bleeding times >8 minutes, but this was not considered to be clinically significant. A total of 24 AEs were reported in 13 of 24 subjects: nausea (3 cases), diarrhea (3), dizziness (3), epigastric discomfort (2), headache (2), rhinorrhea (2), purulent sputum (2), dyspepsia (1), upper abdominal pain (1), cough (1), pharyngolaryngeal pain (1), oropharyngeal swelling (1), dysphonia (1), and dysphagia (1). All were considered mild or moderate in nature. There was no statistically significant difference between the 2 treatments in the number of AEs or in the number of subjects who reported an AE.
CONCLUSION
Administration of a single dose of a combined fixed-dose formulation of ticlopidine 250 mg/ ginkgo extract 80-mg tablets and concomitant administration of ticlopidine and ginkgo extract tablets did not result in statistically significant differences in the pharmacokinetics of ticlopidine in these healthy Korean male volunteers.
Topics: Area Under Curve; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cross-Over Studies; Drug Combinations; Electrocardiography; Ginkgo biloba; Half-Life; Humans; Korea; Male; Mass Spectrometry; Plant Extracts; Platelet Aggregation Inhibitors; Ticlopidine
PubMed: 19922896
DOI: 10.1016/j.clinthera.2009.10.011 -
Acta Anaesthesiologica Scandinavica Feb 2010We designed a prospective randomized single-blind study to compare efficiency and post-operative upper airway morbidity when the laryngeal mask airway (LMA) Supreme is... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
We designed a prospective randomized single-blind study to compare efficiency and post-operative upper airway morbidity when the laryngeal mask airway (LMA) Supreme is used as an alternative to the endotracheal tube (ETT).
METHODS
One hundred and thirty-eight elective pelvic laparoscopic ASA I-II female patients were assigned to receive either the LMA Supreme or the ETT for airway management. Balanced anesthesia and ventilation techniques were standardized to control end-tidal CO(2) and BIS value in the range 4.5-5 kPa and 40-50, respectively, and to maintain adequate hemodynamic stability. A single surgeon blinded to the airway management technique performed all surgical procedures. The ventilation efficiency of each airway was evaluated. Anesthesia- and surgery-related times were calculated and anesthesia details were recorded. Post-operative pain and pharyngolaryngeal morbidity were measured in a blind fashion using a numerical rating scale (NRS) (0-100).
RESULTS
Surgery duration was similar in both groups. Airway management duration was shorter with the LMA Supreme. Post-operative pharyngolaryngeal morbidity incidence and all symptoms' intensity were significantly increased after ETT as compared with LMA Supreme anesthesia. At the end of the PACU stage, the incidence and mean NRS of post-operative hoarseness were reduced when LMA Supreme was used as an alternative to the ETT (16% vs. 47%; P<0.01 and 9 vs. 19, P<0.01, respectively).
CONCLUSION
We demonstrated that choosing an LMA Supreme was an efficient pharyngolaryngeal morbidity-sparing strategy. Moreover, we showed that the LMA Supreme and the ETT were equally effective airways for a routine gynecological laparoscopy procedure.
Topics: Adult; Anesthesia, General; Elective Surgical Procedures; Female; Follow-Up Studies; Gastrointestinal Contents; Gynecologic Surgical Procedures; Hoarseness; Humans; Intubation, Intratracheal; Laparoscopy; Laryngeal Diseases; Laryngeal Masks; Pain Measurement; Pain, Postoperative; Pharyngeal Diseases; Pharyngitis; Postoperative Complications; Prospective Studies; Respiration; Single-Blind Method; Stomach; Suction; Time Factors; Treatment Outcome
PubMed: 19681772
DOI: 10.1111/j.1399-6576.2009.02095.x