Efficacy of add-on montelukast in patients with non-controlled asthma: a Belgian open-label study*

ABSTRACT

Objective: To evaluate the efficacy of add-on montelukast on asthma control and allergic rhinitis symptoms in asthmatic patients still symptomatic with chronic treatment with inhaled corticosteroid and long-acting β₂ agonist (ICS/LABA), irrespective of the dose.

Research design and methods: This 2-month, open-label, real-life, multicentre, observational study was undertaken by 499 general practitioners in Belgium. Patients (≥?4?years old) with uncontrolled asthma despite fluticasone/salmeterol or budesonide/formoterol therapy had oral montelukast 4, 5, or 10?mg daily added to their therapy, depending on the registered dose for their age. Asthma control, assessed by the 6-item Juniper Asthma Control Questionnaire (ACQ) was recorded at baseline and after 2?months of treatment with montelukast and the patients’ global evaluation of asthma was also recorded at the end of the study. Concomitant allergic rhinitis symptoms were evaluated according to the patients’ perception.

Results: A total of 5769 patients were eligible for analysis. Addition of montelukast was associated with significant decrease in mean (SD) ACQ score (from 1.97 [0.77] at baseline to 1.05 [0.69] after add-on treatment, p?<?0.001). There was also a significant improvement in all individual symptoms of the ACQ score (p?<?0.001). After 2?months, 89% of the patients reported global improvement of their asthma, with a good correlation between patients’ global evaluation and change in ACQ scores. Of the 2442 patients who reported allergic rhinitis symptoms at baseline, 91% showed a global improvement of their asthma symptoms and 82% in their rhinitis symptoms after adding montelukast.

Conclusion: This open-label observational study showed an improvement, after 2?months of add-on therapy with montelukast, in both asthma and allergic rhinitis symptoms in patients not adequately controlled on a fixed association of ICS/LABA.     

Cost and utilization of COPD and asthma among insured adults in the US*

ABSTRACT

Objectives: This study evaluates the burden of concomitant chronic obstructive pulmonary disease (COPD) + asthma, two highly prevalent and costly conditions.

Patients and methods: The authors identified commercial enrollees from a large health plan database who were aged ≥40 years with medical and pharmacy benefits and medical claims with diagnosis codes for COPD or asthma between January 1, 2004 and December 31, 2004. We assigned patients to COPD or COPD + asthma cohorts, excluding all others. A patient index date was the first evidence date of COPD or COPD?+?asthma. We excluded those with one outpatient COPD or asthma claim or who were not continuously enrolled during the 12 months before and after index date. After controlling for differences, postindex respiratory-related emergency department (ED) visits and/or hospitalizations and costs were compared between cohorts.

Results: We identified 24,935 patients, 17,394 (70%) in the COPD cohort and 7,541 (30%) in the COPD?+?asthma cohort. COPD?+?asthma patients were younger (58 versus 60 years; p?<?0.0001) and more were females (62% vs 45%; p?<?0.0001). COPD?+?asthma patients were 1.6 times more likely to have respiratory-related EDs and/or hospitalizations than COPD patients (95% CI 1.5, 1.8), and had $1987 (SE?=?$174, p?<?0.0001) more respiratory-related healthcare costs. Mean adjusted respiratory-related healthcare costs were $3803 for COPD and $5790 for COPD?+?asthma. Limitations include a potential for misclassification due to misdiagnosis or coding errors as well as traditional biases of observational studies including the potential for omitted variable bias.

Conclusion: COPD?+?asthma patients are more costly and use more services than those with COPD, and may be more unstable and require more intensive treatment.     

Asthma control in Switzerland: a general practitioner based survey

ABSTRACT

Background: Achievement of optimal asthma control is the goal of the Global Initiative for Asthma (GINA) guidelines.

Methods: In a survey involving 281 physicians, asthma control was assessed using the Juniper asthma control questionnaire (ACQ); physicians were also asked to judge patients’ asthma control subjectively.

Results: In total, 2127 patients were included. Follow-up was available in 1893 (89%) patients (885 females). The mean time between visits was 62 ± 29.3 days; mean age was 45 years (± 19 years) and 30% were smokers. Well-controlled asthma was found in 298 patients (16%). Smokers were less likely to have well-controlled asthma (smokers 12% vs. non-smokers 18%). Physicians assessed asthma control to be good in 292 patients (15%), sufficient in 504 (27%), insufficient in 954 (50%) and poor in 137 (7%) patients. Of the 292 patients assessed by their physicians as ‘good asthma control’, only 142 (49%) were confirmed as ‘well-controlled’ by the ACQ. At the first visit, 1308 (69%) patients were pre-treated with any inhaled corticosteroids (ICS). Pre-treatment with leukotriene receptor antagonists (LTRAs) was reported in 127 patients (7%). Add-on therapy with the LTRA montelukast was the most frequent treatment adjustment at the first visit. Out of 1893 patients who had a follow-up visit, 298 (16%) were well controlled at the first visit and 1170 (62%) at the follow-up visit.

Conclusion: Asthma control is insufficient in the majority of patients. Improvement of asthma control can be achieved by using objective measures such as the ACQ in regular clinical practice and adapting therapy.     

The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis

SUMMARY

Objective: The objective of this study was to evaluate montelukast 10?mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season.

Methods: This was a multicenter study of 831 patients (ages 15?years–85?years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma. Following a single-blind, placebo run-in period of 3?days–5?days, patients were randomized to oral montelukast 10?mg (n = 415) or placebo (n = 416) daily during the 2-week, double-blind, active-treatment period.

Main outcome measures: The primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal Symptoms and Nighttime Symptoms, as self-rated by patients on a 0–3 scale on daily diaries.

Results: Montelukast reduced the Daily Rhinitis Symptoms score: difference between montelukast and placebo in mean change from baseline was –0.12 [95% CI –0.18, –0.06; p ≤ 0.001]. Similar improvements were seen in Daytime Nasal Symptoms (–0.14 [–0.21, –0.07; p ≤ 0.001]) and Nighttime Symptoms (–0.10 [–0.16,–0.04; p ≤ 0.001]). Improvements (p < 0.05) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In exploratory analyses, improvement in rhinitis symptoms was numerically (though not statistically) larger in patients with greater levels of asthma at study start. Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician: mean differences were –0.24 [–0.41, –0.06; p = 0.008] and –0.17 [–0.33,–0.01; p = 0.037]. Similarly, as-needed β-agonist use (puffs/day) was reduced with montelukast (?p ≤ 0.005).

Conclusion: Montelukast provides significant relief from symptoms of seasonal allergic rhinitis, while also conferring a benefit for asthma, in patients with both allergic rhinitis and asthma.     

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study

ABSTRACT

Background: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.

Objective: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care.

Methods: This multicenter, 24?month, pre–post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting β-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy.

Results: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (?p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy.

Conclusions: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.     

A retrospective randomized study of asthma control in the US: results of the CHARIOT study

ABSTRACT

Background: The third version of the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report (EPR-3): Guidelines on the Diagnosis and Management of Asthma emphasizes the need to use asthma control rather than patient severity to base adjustments to treatment and ultimately improve patient outcomes. The objectives of the current study were to assess control of patients with moderate-to-severe asthma, examine the natural history of the disease, practice patterns and resource utilization in specialty community practices according to recently reviewed NAEPP guidelines.

Research design and methods: This analysis represents a retrospective, multicenter, randomized study of 1009 patient charts in sixty United States allergy and pulmonary medicine community practices. The proportion of patients with controlled and uncontrolled asthma over 12 months, prevalence and characteristics of atopy, past asthma history, pulmonary function, medications and treatment patterns, patient and clinical practice characteristics were analyzed.

Main outcome measures: The primary outcome of interest was asthma control.

Results: A total of 365 male and 644 female patients with moderate-to-severe persistent asthma (mean 43.2 ± 17.1 years) were enrolled. 81.9% of patients were uncontrolled according to recent NAEPP guidelines. Importantly, a greater percentage of patients with moderate asthma vs. severe persistent asthma were uncontrolled (p < 0.0114). Atopy was detected in 92% of patients. Patients with early onset of asthma were associated with control (p < 0.0433). Atopic symptoms, such as allergic rhinitis (p < 0.0130) and rhinosinusitis (p < 0.0476), were associated with uncontrolled asthma. Uncontrolled patients were also associated with more medications (a mean of 4.05 ± 1.87 medications) than were controlled patients (a mean of 3.40 ± 1.37 medications (p < 0.0001), although the temporal relationship of this association was not recorded. Limitations may have included patient and/or study site selection bias and difficulty in the process of operationalizing the definitions of control and disease severity. Since the current study only examined patients from specialty practices, the results may not be generalizable to the overall asthma population.

Conclusions: Greater than 80% of asthma patients from specialty practices were uncontrolled with regard to asthma symptoms. Atopic symptoms, such as allergic rhinitis and rhinosinusitis, in addition to a greater number of medications, were associated with uncontrolled asthma. Moreover, patients designated as having asthma of moderate severity were associated with being uncontrolled more than were those with severe asthma (p < 0.0114), which suggests that the former population may not have received adequate assessment of impairment or risk, with subsequent changes in treatment for control of symptoms.     

Evaluation of the tear film instability in children with allergic diseases

Context: The presence of dry eye syndrome (DES) in ocular allergic diseases was evaluated in several studies. Despite this, little exists about the tear film instability in atopic children including patients with allergic rhinitis (AR), allergic conjunctivitis (AC) and asthma. This is a study which presents intriguing findings regarding the relationship of tear film instability with clinical aspects in atopic children.

Objective: To determine the tear film instability in children with AR, AC and asthma.

Materials and methods: One hundred and thirty-five consecutive children with AR, AC and asthma as study group and 45 children without any systemic and ocular abnormality as control group were included in the study. Skin prick tests, measurement of tear film breakup time (TFBUT), serum immunoglobulin E and eosinophil counts were performed in all patients. Also four subgroups of patients were designated as AR group (Group I), AC group (Group II), asthma group (Group III) and control group (Group IV).

Results: Socio-demographic characteristics were similar except for family atopy between the groups (p?>?0.05). The mean TFBUT was significantly lower in the study group (15.5?±?4.4?s) than the control group (18.4?±?2.9?s; p?=?0.000). Also, there was no significant differences in the percentage of the patients who has TFBUT<10?s (p?=?0.066). In logistic regression analysis, atopy was found to be the determinant of lower TFBUT (OR?=?16.33, 95%; CI?=?1.17 to 228.05, p?=?0.03).

Conclusion: The presence of tear film instability was higher in children with AC, AR and asthma. This finding should be taken in consideration in atopic children.     

Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa

ABSTRACT

Objectives: To compare the efficacy and safety of polymyxin sulfate 7500?IU/neomycin sulfate 3500?IU/dexamethasone phosphate 0.1% (PN?+?Dx) otic solution with polymyxin sulfate 7500?IU/neomycin sulfate 3500?IU (PN???Dx) in patients with acute bacterial otitis externa (AOE), in order to determine the possible benefit of the addition of dexamethasone.

Research design and methods: Active controlled, double-blind, randomized, parallel group, multi-center clinical trial in ear, nose, and throat (ENT) specialist practices with a planned interim analysis for sample size adaptation. In total, 338 patients aged 18–76 who had a previous episode of otitis externa within the last year were randomized to receive 10?±?2 days of treatment with two drops, three times daily, of either PN?+?Dx or PN???Dx.

Main outcome measures: Change in the clinical symptom score (consisting of the subscores redness, swelling, pain, and secretion) and of the visual analogue scale (VAS) rating for pain from Visit 1 (Day 1) to Visit 2 (Day 4?±?1), patient's assessment of efficacy at Visit 3 (Day 10?±?2), and the frequency and type of adverse events.

Results: There was a significantly greater reduction of swelling from Visit 1 to Visit 2 with PN?+?Dx, and more patients rated the efficacy of PN?+?Dx as ‘very good’ or ‘good’ at Visit 3 (p?=?0.03). There was also a significantly greater decrease in the clinical symptom score from Visit 1 to Visit 2 in the PN?+?Dx group in patients who had at least a moderately severe symptom score with more than seven points at Visit 1 (p?=?0.01) and in patients suffering from their current episode of otitis externa for more than 2 days (p?=?0.02). In total, 14 adverse events were reported during the study period with no related adverse drug reactions for PN?+?Dx.

Conclusions: The addition of dexamethasone phosphate to polymyxin B/neomycin significantly reduces swelling in patients with AOE and leads to significantly higher patient's ratings of treatment efficacy. It especially leads to an overall reduction of symptoms in cases of moderately or more severe otitis externa and cases lasting for more than 2 days.     

Efficacy and safety of the single pill combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not controlled by amlodipine 10 mg plus olmesartan 20 mg in free combination

ABSTRACT

Background and objective: For patients with moderate hypertension (grade 2, defined as systolic blood pressure [SBP] 160–179?mmHg and/or diastolic blood pressure [DBP] 100–109?mmHg), current guidelines recommend initial combination therapy and rapid dose-adjustment to achieve blood pressure goal. In this study we investigated the efficacy and tolerability of the single pill combination of amlodipine 10?mg plus valsartan 160?mg (A?10?+?Val 160) in patients not controlled by the free combination of amlodipine 10?mg plus olmesartan 20?mg (A?10?+?O 20).

Methods: In this prospective, open-label, non-randomized trial, 257 patients with mean sitting DBP of 100–109?mmHg at trough entered a 4 week treatment phase with A?10?+?O 20 in free combination once daily. Patients in whom DBP remained uncontrolled were switched in a second 4 week treatment phase to A?10?+?Val 160. The primary efficacy variable was the reduction in DBP at week 8 compared to week 4 in the intent-to-treat population.

Results: In the total cohort, baseline SBP/DBP of 164.2?±?9.8/103.6?±?2.1?mmHg decreased by 19.2?±?12.4/14.1?±?7.4?mmHg at week 4. In patients who did not achieve BP control (n?=?175), subsequent treatment with A?10?+?Val 160 for 4 weeks reduced SBP from 149.6?±?11.1 at week 4 by 7.9?mmHg at week 8 (95% CI: 6.1–9.6, p?<?0.0001) and DBP from 93.4?±?3.9?mmHg by 9.1?mmHg (95% confidence interval: 8.1–10.2, p?<?0.0001). The combination of A?10?+?Val 160 was well tolerated, and the observed adverse events (15.3% of patients in phase 2) were consistent with the known drug profiles.

Conclusions: In a study designed to reflect typical clinical practice, in patients not controlled by the free combination of A?10?+?O 20, the single pill combination of A?10?+?Val 160 produced a statistically and clinically significant additional BP reduction and was well tolerated. Potential limitations of the design (open-label, non-controlled design, short term treatment) have to be taken into account.     

Comparison of costs of sublingual immunotherapy and drug treatment in grass-pollen induced allergy: results from the SIMAP database study

ABSTRACT

Objectives: This analysis is focused on the comparison of costs of allergic rhinitis (R) alone or with allergic asthma (R?+?A) in grass pollen allergy, for subjects treated with sublingual immunotherapy (SLIT) and symptomatic drugs, versus standard care controls.

Methods: The SIMAP (Sublingual IMmunotherapy in Allergic Patients) study is a longitudinal observational database operated by a network of Allergy centers. Patients suffering from grass pollen allergy were included in this analysis and assigned to SLIT (plus drugs as needed) or to treatment with drugs alone. Outcome measures included use of medications, SLIT, visits and tests. Costs were assessed from the perspective of the Italian National Health Service; unit costs were obtained from published sources to produce an average cost/patient for the first year after enrolment.

Results: One hundred and two patients were analyzed. Demographics were comparable in the two groups. Overall per patient yearly cost of treatment was higher in SLIT patients, both in the whole sample (€311 vs. €180/patient), in the R (€288 vs. €116) and R?+?A (€362 vs. €230) subpopulations, with R?+?A patients generating more costs than R patients in both groups. Nevertheless considerable savings were obtained in the cost of symptomatic drugs (?22% for R; ?34% for R?+?A) in SLIT patients.

Conclusions: Other studies have shown that SLIT can reduce the use of drugs for asthma and rhinitis, but this is the first time this outcome has been demonstrated in a routine care population (in the medical practice environment of an observational study) within the first year of treatment.     

Observational study of sublingual specific immunotherapy in persistent and intermittent allergic rhinitis: the EFESO trial

ABSTRACT

Background: Sublingual specific immunotherapy (SLIT) is a valid treatment for allergies. However, there are few data on a large sample size regarding its clinical role in ‘real life’.

Study aim: We performed a multicentre, case-control study to evaluate the effectiveness of SLIT in patients with allergic rhinitis (AR).

Methods: A total of 305 patients with AR were enrolled. Cases (n?=?154) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated daily for at least two consecutive years with specific SLIT. Controls (n?=?151) were defined as age-, sex- and type of allergen-matched AR subjects who were never treated with specific immunotherapy. The main outcomes of the study were the rhinoconjunctivitis symptom score (SS) and the symptomatic medication score (MS). SS and MS were evaluated at the end of the observational period in relation to the peak of relevant pollen season or during the period of maximum allergen exposure in case of non-seasonal allergens.

Results: SS mean (SD) value was 5.1 (3.0) in cases and 9.3 (3.3) in controls (?43%) (?p?=?0.0001). MS mean (SD) value was 2.6 (1.8) and 4.4 (2.6) in the case and control groups, respectively (?41%) (?p?=?0.0001). At the end of the observation period, asthma-related symptoms were present in 8.5% of cases and in 20% in the control group (?p?=?0.01).

Conclusion: The EFficacia nella rinitE allergica di SlitOne (EFESO) trial shows that SLIT treatment in AR is associated with lower SS and MS in comparison with controls. SLIT is also associated with a lower incidence of asthma and new sensitizations. As this was an observational study, our results need to be confirmed in randomized, double-blind, controlled trials.     

Efficacy of Omalizumab,an Anti-immunoglobulin E Antibody,in Patients with Allergic Asthma at High Risk of Serious Asthma-related Morbidity and Mortality

Summary

Aim: Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality.

Methods: A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n?=?135; placebo, n?=?119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies).

Results: Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p?=?0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p?=?0.026), overall AQoL (p?=?0.042) and mean nocturnal (p?=?0.007) and mean total (p?=?0.011) asthma symptom scores compared with placebo.

Conclusions: In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.     

Impact of Montelukast on Symptoms in Mild-to-Moderate Persistent Asthma and Exercise-Induced Asthma: Results of the ASTHMA Survey

Summary

A nation-wide survey was undertaken in Belgium among general practitioners (GPs) to evaluate the impact of the leukotriene receptor antagonist (LTRA) montelukast on the control of asthma symptoms, after at least 4 weeks of treatment. Patients from 6 years of age were eligible if they were suffering from mild-to-moderate persistent asthma which was still symptomatic despite inhaled corticosteroids (ICS) treatment, or from exercise-induced asthma. Patient general satisfaction was evaluated by recording the willingness to continue the treatment. A total of 1360?GPs took part in the study and more than 11 000 patients were included in the survey.

Of the included patients, 85% were receiving inhaled corticosteroids, 60% of whom were also on long-acting β2-agonists (LABA). However, despite the use of daily controller medication, 92% of the patients still reported limitation of activities, 49% difficulties with sleep and 45% early morning awakening due to asthma. Moreover, 78% of the patients used rescue medication more than twice a week.

At the end of the survey, 90% of the patients expressed their willingness to continue montelukast therapy. Of the patients having symptoms at the start of the study, 87% reported amelioration in sleep while on montelukast therapy, 80% less frequent early morning awakening, 85% better ability to perform daily activities and 77% decreased need for rescue medication.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.     

Antiallergic effect of piperine on ovalbumin-induced allergic rhinitis in mice

Abstract

Context: Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.

Objective: The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.

Materials and methods: Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40?mg/kg, p.o.), or montelukast (10?mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1β), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action.

Results: PIP (10, 20, and 40?mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p?<?0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p?<?0.001), as well as reduced expression of IL-6, IL-1β, and IgE (p?<?0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p?<?0.001).

Discussion and conclusion: PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.     

Osmotically controlled pulsatile release capsule of montelukast sodium for chronotherapy: Statistical optimization,in vitro and in vivo evaluation

Abstract

The purpose of present study was to design, optimize and evaluate osmotically controlled pulsatile release capsule (PRC) of montelukast sodium (MKS) for the prevention of episodic attack of asthma in early morning and associated allergic rhinitis. Assembly of the capsular systems consisted of push, active and plug tablet arranged from bottom to top in hard gelatin capsule. The capsule system was coated with a semi-permeable membrane of cellulose acetate and drilled towards plug side in cap. A three-factor, three-level central composite design (CCD) with α?=?1 was introduced to execute the experiments and quadratic polynomial model was generated to predict and assess the independent variables with respect to the dependent variables. The composition of optimal formulation was determined as weight of push tablet 138?mg (coded value: +0.59), plug tablet 60?mg (coded value: +0.49) and coating weight gain of 8.4?mg (coded value: ?0.82). The results showed that the optimal formulation of PRCs had lag time of 4.5?h, release at 6 and 12?h are 61.95% and 96.29%, respectively. The X-ray radiographic imaging study was carried out to monitor the in vivo behavior of developed barium sulfate-loaded PRCs in rabbits under fasting conditions. In vivo pharmacokinetic study revealed T_max of 2?h for marketed tablets; however 7?h for PRCs with initial lag time of 4?h. Thus designed capsular system may be helpful for patients with episodic attack of asthma in early morning and associated allergic rhinitis.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting β2‐agonists: addition of montelukast in an open-label pilot study

ABSTRACT

Background: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit.

Objective: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA.

Methods: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (≥ 15 years old) suffering from persistent asthma (pre-bronchodilator FEV₁ ≥ 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10?mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians.

Results: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 ± 5.1 at baseline versus 7.4 ± 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (?p < 0.001) and in pre-bronchodilator FEV₁ score (from 2.2 ± 1.5 to 1.6 ± 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (κ = 0.66).

Conclusion: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

Improvement in quality of life with omalizumab in patients with severe allergic asthma

ABSTRACT

Background: Patients with severe persistent asthma experience daily symptoms and frequent serious exacerbations that contribute to a significant impairment of health-related quality of life (QoL).

Methods: A pooled analysis was completed of six controlled clinical trials that evaluated the effect of add-on omalizumab on asthma-related QoL in patients with severe persistent allergic (IgE-mediated) asthma. Asthma-related QoL was assessed at baseline and treatment endpoint using the well-validated Juniper Asthma Quality of Life Questionnaire (AQLQ). Change from baseline in AQLQ total score was compared between treatments using analysis of covariance methods. The percentage of patients who achieved a clinically meaningful (≥ 0.5-point) improvement in AQLQ total score was compared using the Mantel–Haenszel Chi-square test.

Results: The pooled patient population comprised 2548 patients (omalizumab, n = 1342; control, n = 1206), of whom 96% had severe persistent asthma according to the GINA 2002 classification. Omalizumab produced significantly greater improvements in AQLQ total score vs the control group (mean increases of 1.01 and 0.61 points, respectively; p < 0.001). In addition, significantly more omalizumab-treated patients achieved a clinically meaningful improvement in AQLQ total score than patients in the control group (66.3% vs 52.4%; p < 0.001).

Conclusions: Add-on therapy with omalizumab improves QoL to a significant and clinically meaningful level in patients with severe persistent allergic asthma.