Long-term safety and efficacy studies of epinephrine HFA metered-dose inhaler (Primatene® Mist): a two-stage randomized controlled trial.

Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reformulated to replace the previously marketed epinephrine chlorofluorocarbon (CFC) MDI. In addition to the HFA propellant change, several enhanced modifications (i.e. changed from solution to suspension, 43% dose reduction, etc.) were made to the formulation of epinephrine HFA MDI. This study evaluates the 6-month long-term safety and efficacy profile of the new epinephrine HFA MDI.Method: The long-term safety study consists of two 3-month, multi-center, double- or evaluator-blinded, parallel-group, placebo, and active controlled stages. In each stage, subjects aged ≥12 years with intermittent or mild-to-moderate persistent asthma were randomized to receive epinephrine HFA (2 × 125 mcg/inhalation), placebo HFA, or epinephrine CFC (2 × 220 mcg/inhalation). Bronchodilator efficacy was assessed in Stage 1 and was determined primarily by the change in the forced expiratory volume in 1 s (ΔFEV1) at Week 12, relative to the same day baseline.Results: The primary efficacy endpoint (AUC0-6hrs of %ΔFEV1 at Week 12) for epinephrine HFA (47.3 ± 54.2) closely paralleled those for the active control, epinephrine CFC (41.0 ± 43.4). Both groups were found to be overall comparable in bronchodilator efficacy. Both also showed low incidence rates of AEs with tremor being most commonly reported for epinephrine HFA. All AEs found were non-serious and non-significant. The observed changes in vital signs, ECG, serum glucose, and potassium were minimal and not clinically relevant.Conclusion: This study demonstrated that the new epinephrine HFA is overall comparable, in both safety and efficacy, to the previous epinephrine CFC.

Lebrikizumab treatment in adults with asthma.

BACKGROUND: Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity. METHODS: We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level. RESULTS: At baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 µg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P = 0.045). CONCLUSIONS: Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163 .).

Beclomethasone dipropionate nasal aerosol with an integrated dose counter: functionality and performance.

Consistent medication delivery is critical for disease control including symptom management of allergic rhinitis (AR). Available aqueous intranasal corticosteroid devices lack an accurate dose (actuation) counter, which may lead patients to prematurely discard a unit or use a unit beyond its labeled number of actuations, therefore impacting patient adherence. Beclomethasone dipropionate (BDP) nasal aerosol, a nonaqueous hydrofluoroalkane formulation in a device with a novel integrated dose counter and an established efficacy/safety profile, was approved to treat AR-associated nasal symptoms in adolescent and adult patients. This study was designed to evaluate performance of the BDP nasal aerosol device with an integrated dose counter in perennial AR (PAR) patients. In a 6-week, double-blind, placebo-controlled study in PAR patients (≥12 years), patients were randomized to receive once-daily BDP nasal aerosol at 320 micrograms or placebo. In addition to assessing the primary efficacy end point, patients evaluated the performance of the device and reliability, accuracy, and functionality of the dose counter. Concordance between daily patient-reported actuations and dose counter readings was assessed by classifying discrepancies into four categories: "fire not count," "count not fire," "count unknown fire," and "count up unknown fire." Analysis was performed for the total device completer population (n = 374), which included all randomized patients completing ≥80% of actuations during the last 4 weeks of treatment. Low discrepancy rates were shown for all discrepancy categories. Of 41,891 patient-reported actuations, only 159 discrepancies (diary versus counter) were noted, resulting in an overall discrepancy rate of 0.38 per 100 actuations. The medically important discrepancy rate of "fire not count" was low (0.09 per 100 actuations). Overall, 79.1% of patients reported zero discrepancies, 9.4% reported one discrepancy, and 6.4% reported two discrepancies. These results showed the functionality and reliability of the BDP nasal aerosol device with an integrated dose counter in a clinical setting. (ClinicalTrials.gov identifier: NCT01134705.).

Nasal carbon dioxide for the symptomatic treatment of perennial allergic rhinitis.

BACKGROUND: Brief nasal carbon dioxide insufflation has previously been shown to provide rapid relief of the symptoms of allergic rhinitis. OBJECTIVE: To examine the safety and efficacy of nasal carbon dioxide on the symptoms of perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, multicenter, in-clinic study that evaluated 2 flow rates (5 or 10 mL/s) and 2 administration durations (10 or 30 seconds per nostril) for nasal carbon dioxide vs placebo. Study participants rated their symptoms in clinic for 4 hours after administration and then through 24 hours outside the clinic. A total of 348 symptomatic patients with a minimum 2-year history of perennial allergic rhinitis requiring pharmacotherapy were randomized and treated. RESULTS: The mean change in total nasal symptom score from baseline at 30 minutes (the primary end point) showed greater improvement in the nasal carbon dioxide-treated groups compared with placebo. This change was statistically significant in the group treated with 10 mL/s for 10 seconds per nostril: -4.69 carbon dioxide vs -2.00 placebo (P = .03). The effect of a single dose lasted approximately 4 to 6 hours. The mean change from baseline at 30 minutes in total nonnasal symptom score was also statistically significant (-4.06 carbon dioxide vs -2.25 placebo, P = .029) for this group. The most common adverse events were nasal discomfort, lacrimation, and headache. CONCLUSION: The study provides further evidence that nasal carbon dioxide is a potentially efficacious treatment for the symptoms of allergic rhinitis.

A phase I randomized, placebo-controlled, dose-exploration study of single-dose inhaled montelukast in patients with chronic asthma.

BACKGROUND: The efficacy of oral montelukast has been well established in asthma and allergic rhinitis in adults and children. The purpose of this study was to evaluate dose-related bronchodilation and tolerability of inhaled montelukast. METHODS: Randomized, double-blind, crossover, adaptive-design study comparing single-dose administration of inhaled montelukast versus placebo in patients age 15-65 years with chronic asthma (n = 68). Montelukast was delivered as a witnessed dose through dry powder inhaler at doses of 25, 250, or 1000 µg, and doses of 50, 100, and 500 µg could be used if needed based on a prespecified dose-response algorithm. Each administration was followed by a 4- to 7-day washout period before crossing over to the next treatment. The primary endpoint was the change from baseline in a forced expiratory volume in 1 second (FEV1) over the first 4 hours after administration, calculated as a time-weighted average (ΔFEV1 [0-4 hours]). Other endpoints included the onset and duration of bronchodilation and the effect of albuterol when added to inhaled montelukast. RESULTS: Over 4 hours postdose, and compared with placebo (least-squares [LS] mean 0.03 L), inhaled montelukast 100 µg (0.13 L; p ≤ .001), 250 µg (0.10 L; p < .01), and 1000 µg (0.12 L; p ≤ .001) had significantly greater ΔFEV1 (0-4 hours). At 24 hours postdose, inhaled montelukast 100 µg (0.10 L) and 1000 µg (0.09 L) had significantly greater bronchodilation compared with placebo (0.02 L; p < .05 vs. montelukast). Montelukast 1000 µg provided significant bronchodilation versus placebo within 20 minutes of administration (0.03 L vs. -0.05 L), whereas montelukast 100 µg provided significant bronchodilation relative to placebo within 2 hours of dosing (0.09 L vs. 0.01 L). Montelukast (pooled doses) plus albuterol was significantly more effective than montelukast plus placebo for ΔFEV1 (0-90 minutes) (0.34 L vs. 0.15 L; p = .015). The tolerability of inhaled montelukast was similar to that of placebo. No serious adverse experiences were reported. CONCLUSIONS: Inhaled montelukast provided significant bronchodilation compared with placebo as early as 20 minutes after the administration that persisted for 24 hours and provided additive bronchodilation to albuterol.

Budesonide/formoterol pressurized metered-dose inhaler for patients with persistent asthma.

The combination of budesonide and formoterol administered in one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) is approved in the United States in two dosage strengths (budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations [160/9 microg] or 160/4.5 microg x 2 inhalations [320/9 microg]) in a fixed-dose, twice-daily regimen for the treatment of patients > or =12 years old with persistent asthma not adequately controlled with an inhaled corticosteroid (ICS) alone. This article reviews the clinical profile of budesonide/formoterol pMDI in patients with persistent asthma, including information on pharmacogenetics, efficacy, and tolerability. Studies of budesonide/formoterol pMDI in patients with asthma were identified through PubMed and respiratory meeting abstract databases. Budesonide/formoterol pMDI 160/9 microg has shown a rapid onset (within 15 minutes) of clinically significant bronchodilation that is faster than fluticasone propionate/salmeterol dry powder inhaler (DPI) 250/50 microg (within 30 minutes). The efficacy and tolerability profile of budesonide/formoterol pMDI 320/9 microg was similar to fluticasone propionate/salmeterol DPI 250/50 microg and budesonide/formoterol DPI 320/9 microg in adults and adolescents with persistent asthma. Short-term (12-week) and long-term (6- to 12-month) studies have established greater efficacy and similar tolerability of budesonide/formoterol pMDI compared with its monocomponents and placebo in patients with mild/moderate or moderate/severe persistent asthma. Studies evaluating patient-reported outcomes, including health-related quality of life and patient satisfaction with treatment, further support the benefits of budesonide/formoterol pMDI in patients with persistent asthma. In summary, budesonide/formoterol pMDI is an effective, well-tolerated treatment option for patients with persistent asthma for whom ICS/long-acting beta2-adrenergic agonist combination therapy is appropriate.

Nasal Carbon Dioxide Used As Needed in the Symptomatic Treatment of Seasonal Allergic Rhinitis.

BACKGROUND: Nasal, noninhaled carbon dioxide (CO2) was shown to be effective for the treatment of symptoms of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis in single application studies. OBJECTIVE: To assess the efficacy of as-needed treatment with nasal, noninhaled CO2 in patients with SAR. METHODS: Fifty-six ragweed-allergic patients were enrolled at 3 sites in this study. After a 3- to 7-day run-in, 32 eligible patients who had an instantaneous total nasal symptom score of 8 or more out of a maximum of 12 in at least 2 SAR episodes per day were randomized to the CO2 group (n = 19) or to the placebo group (n = 13). A 10-second/nostril application was used as needed for 14 days (maximum 6 times/d). Patients evaluated their symptoms before and 30 minutes after each application. All symptoms were scored on a 0 to 3 scale. RESULTS: Analysis of all treated episodes (CO2 = 816, placebo = 516) showed a statistically significant beneficial change in total nasal symptom score from baseline (effect size = -0.51; P < .001). The effect size was larger with more severe baseline symptoms (baseline severities of ≥6 = -0.98; ≥8 = -1.14; and ≥10 = -1.61; all P < .001). CO2 was well tolerated, with transient nasal discomfort as the most common adverse event reported. There were no serious adverse events, serious adverse device effects, or early discontinuations. CONCLUSIONS: Nasal, noninhaled CO2 is effective for the as-needed treatment of SAR symptoms. The effect is rapid and the effect size is large. It represents a novel potential option for the as-needed treatment of rhinitis symptoms.

Twelve-week, randomized, placebo-controlled, multicenter study of the efficacy and tolerability of budesonide and formoterol in one metered-dose inhaler compared with budesonide alone and formoterol alone in adolescents and adults with asthma.

BACKGROUND: The addition of the long-acting beta(2)-adrenergic agonist formoterol to low- to moderate-dose budesonide has shown clinical efficacy in patients with persistent asthma. Combination therapy with budesonide/formoterol in 1 pressurized metered-dose inhaler (pMDI) has been found to have greater efficacy than its monocomponents in patients with moderate to severe persistent asthma, but it has not been assessed in patients with mild to moderate persistent asthma. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of budesonide and formoterol delivered via 1 pMDI (budesonide/formoterol pMDI), budesonide pMDI, formoterol dry powder inhaler (DPI), and placebo. METHODS: This 12-week, multicenter, double-blind, randomized, placebo-controlled, double-dummy study was conducted at 56 centers across the United States. Patients aged > or =12 years with mild to moderate persistent asthma treated with inhaled corticosteroids (ICSs) for > or =4 weeks before screening and who had a forced expiratory volume in 1 second (FEV(1)) of > or =60% to < or =90% of predicted normal at screening were eligible. After 2 weeks (current asthma therapy discontinued), patients received twice-daily budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), budesonide pMDI 80 microg x 2 inhalations (160 microg), formoterol DPI 4.5 microg x 2 inhalations (9 microg), or placebo. The coprimary efficacy variables were changes from baseline in morning predose FEV(1) and 12-hour mean FEV(1) (from serial spirometry) after administration of the morning dose of study medication. Tolerability was assessed based on adverse events (AEs); routine laboratory assessments; electrocardiography; 24-hour Holter monitor assessments; and physical examinations, including vital signs (eg, systolic and diastolic blood pressure and heart rate). AEs were recorded manually by the patient in paper notebooks and reviewed at each clinic visit by the investigator and during a final follow-up phone call. RESULTS: A total of 480 patients were randomized (299 females, 181 males; mean age, 36 years; mean FEV(1), 2.4 L; budesonide/formoterol pMDI, 123 patients; budesonide pMDI, 121; formoterol DPI, 114; placebo, 122). At end of treatment, the mean increases from baseline in predose FEV(1) were greater with budesonide/formoterol pMDI versus budesonide pMDI, formoterol DPI, and placebo (0.37 vs 0.23, 0.17, and 0.03 L, respectively; all, P<0.005). 0.005). After administration of the first dose and at weeks 2 and 12, mean increases in 12-hour mean FEV(1) were significantly greater with budesonide/formoterol pMDI (0.41, 0.47, and 0.50 L, respectively) versus budesonide pMDI (0.17, 0.30, and 0.32 L) and placebo (0.15, 0.12, and 0.12 L) (all, P < 0.001). Fewer patients receiving budesonide/formoterol pMDI met criteria for (18.7%; P < 0.001) or withdrew because of (7.3%; P < or = 0.010) worsening asthma versus formoterol DPI (42.1% and 18.4%, respectively) and placebo (56.6% and 32.8%); results were similar between budesonide pMDI (21.5% and 6.6%, respectively) and budesonide/formoterol pMDI. Three patients experienced serious AEs; none was considered related to study medication. The proportions of withdrawals due to worsening asthma were not significantly different between the budesonide/formoterol pMDI and budesonide pMDI groups. CONCLUSIONS: In this population of adults and adolescents with mild to moderate persistent asthma previously treated with ICSs, twice-daily budesonide/formoterol pMDI was associated with significantly increased pulmonary function versus its monocomponents. All study drugs were generally well tolerated.

Treating asthma in the older patient: is there a place for leukotriene modifiers?

Asthma is a common airway disease found in people of all ages, although most studies of asthma therapies are focused on adolescent and young adults. Little information exists on the use of asthma therapeutics in the older patient (>65 years of age). The newest therapeutic class to be released in the US for the treatment of asthma is the leukotriene modifiers. These medications (either receptor antagonists or enzyme inhibitors) have been found to be beneficial in younger patients with asthma, but their potential role in older patients is less clear. In this review, the data regarding the use of these medications in older patients are examined, as are the epidemiological and pathophysiological issues regarding asthma in this growing patient population. On the basis of the two published reports of leukotriene modifiers in the older patient, we conclude that leukotriene modifiers are useful in this population, but like other controller therapies for asthma, they are less effective in the older population.

Zafirlukast treatment for acute asthma: evaluation in a randomized, double-blind, multicenter trial.

CONTEXT: Acute asthma causes nearly 2 million hospital emergency department (ED) visits in the United States annually, and hospitalization after an ED visit and relapse after ED discharge are common. OBJECTIVE: To evaluate the adding of therapy with zafirlukast to standardized care for patients with acute asthma in the ED and a 28-day follow-up period. DESIGN AND PATIENTS: A total of 641 patients presenting to the ED with acute asthma were randomized to receive either single-dose zafirlukast, 160 mg (Z160) [162 patients], zafirlukast, 20 mg (Z20) [158 patients]), or placebo (321 patients) as adjunct treatment to standard care in this double-blind, multicenter trial. Assessments, including spirometry and symptom scores, were obtained before each albuterol treatment and at 4 h. Patients who were discharged from the ED after 4 h continued outpatient therapy over a 28-day period and received either Z20 bid (276 patients) or placebo (270 patients) in addition to prednisone, albuterol, and their previous asthma medications. FEV(1) was measured at clinic visits on days 10 and 28. Patients recorded outpatient clinical data twice daily on a home diary card. MAIN OUTCOME MEASURES: the effect of zafirlukast on relapse after ED discharge. Other assessments were the rate of extended care (ie, ED stay for > 4 h or hospitalization), FEV(1), and symptoms. RESULTS: At the end of the outpatient period, 65 of 276 patients (23.6%) treated with zafirlukast and 78 of 270 patients (28.9%) treated with placebo relapsed (p = 0.047; absolute reduction, 5.3%; relative reduction, 18.3%). At the end of the ED period, 16 of 162 patients (9.9%) treated with Z160, 26 of 158 patients (16.5%) treated with Z20, and 48 of 321 patients (15.0%) treated with placebo required extended care (p = 0.052; absolute reduction with Z160 compared to placebo, 5.1%; relative reduction, 34%). These findings were supported by a significant improvement in FEV(1) and dyspnea in the ED with the use of Z160 therapy, and by greater improvement in FEV(1) and symptoms during the outpatient period for patients treated with Z20. CONCLUSIONS: When added to standardized care, therapy with Z20 bid reduced the risk of relapse compared with placebo over a 28-day treatment period. One dose of Z160 in the ED also reduced the rate of extended care.

Anti-interleukin 4 and 13 for asthma treatment in the era of endotypes.

PURPOSE OF REVIEW: To summarize recent advances in IL-4 and IL-13 blockade in the treatment of asthma. RECENT FINDINGS: Historically, anticytokine therapies have historically been unsuccessful in the treatment of asthma because of the heterogeneity of its pathogenesis. Recent advances in our understanding of asthma pathophysiology and our increased ability to phenotype patients have led to the identification of asthmatic subsets (endotypes) that are most likely to respond to anticytokine therapy. Several new biologic therapies targeting IL-13 or both IL-4 and IL-13 signaling are currently in clinical trials and both types of therapies have demonstrated therapeutic benefit. SUMMARY: Anti-IL-4/13 therapies, guided by knowledge of an individual's underlying pathophysiology, are a promising class of therapies for treatment of asthma.

Ciclesonide and the treatment of asthma.

IMPORTANCE OF THE FIELD: Asthma is a chronic disease characterized by airway inflammation and hyper-responsiveness. Inhaled corticosteroids (ICSs) constitute the guideline-recommended first-line therapy for persistent asthma. However, concerns regarding ICS-related adverse events may contribute to their underutilization by physicians and patients. AREAS COVERED IN THIS REVIEW: The currently available published data on the pharmacokinetic and pharmacodynamic properties, safety and efficacy of the ICS, ciclesonide, is described. Peer-reviewed publications (1996 - 2009) on the pharmacodynamic and pharmacokinetic profile, safety and efficacy of ciclesonide were reviewed. WHAT THE READER WILL GAIN: Ciclesonide is delivered as an inactive prodrug, which is cleaved to the active molecule by intracellular esterases located in the lungs. This and other pharmacodynamic and pharmacokinetic properties may limit the amount of active molecule outside the lung and may reduce the incidence of side effects. Randomized placebo-controlled studies found that ciclesonide can initiate and maintain disease control in subjects with persistent asthma of all disease severities. Moreover, studies have found that ciclesonide is as effective as other ICSs in establishing and controlling disease symptoms. Controlled clinical trials also showed that ciclesonide is associated with minimal systemic and local treatment-related adverse events. TAKE HOME MESSAGE: Published findings indicate that ciclesonide is effective at initiating and maintaining asthma control and is well tolerated, with a positive safety profile.

Efficacy and safety evaluation of ciclesonide in mild-to-moderate persistent asthma previously treated with inhaled corticosteroids.

Inhaled corticosteroids (ICSs) are recommended as first-line treatment for persistent asthma. This study was designed to evaluate the ability of ciclesonide (CIC) in subjects with stable asthma previously receiving another ICS or ICS/long-acting beta(2)-agonist (LABA) to maintain asthma disease control. In this 12-week, multicenter, double-blind, parallel-group study, subjects aged > or =12 years with stable mild-to-moderate persistent asthma were switched at randomization from an ICS or ICS/LABA to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 149); CIC, 160 microg once daily (CIC160 q.d.; n = 150); or placebo (n = 147). Change in forced expiratory volume in 1 second (FEV(1); primary end point), morning peak expiratory flow (PEF), rescue albuterol use, total asthma symptom score, nighttime awakenings, and safety were evaluated. FEV(1) improved from baseline to week 12 after CIC80 b.i.d. treatment (+0.07 L; p = 0.0232), and was maintained after CIC160 q.d. (+0.01 L; p = 0.6217). FEV(1) declined from baseline after placebo (-0.12 L; p < 0.0001) and significantly versus CIC treatments (p < 0.001). At week 12, morning PEF maintained baseline values after CIC80 b.i.d. (-4.43 L/minute; p = 0.1272) and decreased after CIC160 q.d. (-5.77 L/minute; p = 0.0490) and placebo (-12.82 L/minute; p < 0.0001); the difference between CIC80 b.i.d. and placebo was significant (p = 0.035). Baseline albuterol use, total daily asthma score, and nighttime awakenings were maintained after CIC treatments (p > 0.25), but increased after placebo (p < or = 0.002); the difference between CIC80 b.i.d. and placebo was significant (p < 0.02). Incidence of adverse events was similar among treatment groups (range, 52.0-57.9%). In this study, CIC80 b.i.d. maintained asthma control in subjects with stable mild-to-moderate asthma previously treated with ICS or ICS/LABA, was well tolerated, and, in general, was better than CIC160 q.d. in maintaining disease control.

The role of antileukotriene drugs in management of rhinitis and rhinosinusitis.

Antileukotriene drugs have been studied for more than 15 years. In this review we examine the role of leukotrienes in rhinitis and rhinosinusitis, and explore the clinical literature supporting the use of anti-leukotriene agents in these diseases. Although these medications clearly are efficacious in rhinitis, it is unclear where in the armamentarium they should be used. The evidence for use in sinusitis has not been well studied except in sinusitis-associated aspirin-exacerbated respiratory disease. In this circumstance there is information that allows use of antileukotriene agents to be considered efficacious. We provide our rationale for use and await future clinical studies to answer this important question.

The emerging role of leukotriene modifiers in allergic rhinitis.

Leukotriene modifiers have been shown to be efficacious in the treatment of asthma. Because of this success, and the fact that leukotrienes can be recovered not only from bronchoalveolar lavage fluid but also nasal lavage fluid, some researchers have suggested that these medications may also be useful for treating allergic rhinitis. Because the upper and lower airways are linked physically, there has been an assumption that therapy for upper and lower airway disease should be similar. This critical appraisal examines available data both supporting and refuting the emerging role of leukotriene modifiers in the treatment of allergic rhinitis. Although many studies have shown an improvement in nasal symptoms when comparing a leukotriene modifier with placebo, few studies have conclusively shown that a leukotriene modifier is any more effective in treating allergic rhinitis than an antihistamine. Results from several reported studies suggest that the addition of a leukotriene antagonist to an antihistamine is no more efficacious than antihistamine alone. However, many of these studies were small and/or primarily designed to examine the asthmatic response, with nasal symptoms being a lesser endpoint. To better understand how, where, and when leukotriene modifiers should be used in the armamentarium of therapies for allergic rhinitis, larger clinical investigations designed specifically to study allergic rhinitis need to be undertaken. We conclude that currently, the data do not support widespread use of a leukotriene modifier with or without an antihistamine in place of an intranasal corticosteroid with or without an antihistamine in the treatment of allergic rhinitis.