Onset of action is recognized as an important pharmacologic property of allergic rhinitis (AR) medications. This study was designed to evaluate the onset of action of loratadine/montelukast (L/M; 10 mg/10 mg) versus placebo in subjects with ragweed-induced seasonal AR (SAR). A single-center, double-blind, parallel-group study of ragweed-sensitive AR subjects (n = 310) was performed in the Environmental Exposure Unit (EEU). Subjects were exposed to ragweed pollen in the EEU and symptoms were recorded at 30, 60, 90, and 120 minutes before a single dose of L/M or placebo. After dosing, symptoms were recorded for 4 hours, at 15-minute intervals for the first 2 hours and at 30-minute intervals for the final 2 hours. The primary end point was time to onset of action of L/M, defined as the first time point at which the mean change from baseline in total symptom score (TSS) for L/M became and remained significantly better than placebo. Secondary end points included nasal congestion scores and peak nasal inspiratory flow (PNIF). The onset of action of L/M for TSS was 1 hour and 15 minutes (p = 0.005 versus placebo). L/M reduced nasal congestion as indicated by significant improvements in both the nasal congestion score (p = 0.011) and the PNIF measurements (p = 0.007) within 1 hour and 15 minutes postdose. The incidence of treatment-emergent adverse events was similar between groups. The onset of action after treatment with L/M was 1 hour and 15 minutes for TSS, as well as nasal congestion. L/M was well tolerated.

RATIONALE: Mometasone furoate nasal spray (MFNS) is effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR). A reanalysis of patient-reported symptom data in MFNS trials was performed to determine its impact on ocular symptoms.METHODS: Ocular symptom data were pooled from 4 randomized, double-blind, placebo-controlled, phase III clinical studies (three 2-week; one 4-week); these studies followed similar protocols which compared the effectiveness of MFNS 200 mcg qd and placebo in controlling ocular symptoms in patients ≥aged 12 years with a ≥2-year history of SAR (N=983). Individual sign/symptom scores for eye tearing, itching, and redness were evaluated on a 4-point scale (0=none; 3=severe), and a total ocular symptom score (TOSS) was calculated.RESULTS: The mean baseline TOSS was 4.35 for the MFNS group and 4.5 for the placebo group. The MFNS group (n=491) showed greater decreases in TOSS than the placebo group (n=492) starting at Day 2, first reaching statistical significance at Day 3. The decrease with MFNS for the Day 1-15 interval was 19.8% vs 5.6% for placebo (P<0.001). For the same time period, the scores for tearing decreased by 22.2% with MFNS vs a decrease of 3.9% with placebo (P<0.001), for eye itching by 17.3% with MFNS vs 12.3% with placebo (P=0.002), and for redness by 15.7% with MFNS vs 8.3% with placebo (P=0.002).CONCLUSIONS: MFNS successfully reduced ocular symptoms of SAR. The effects of MFNS on these ocular symptoms are consistent with results reported with other intranasal steroids. RATIONALE: Mometasone furoate nasal spray (MFNS) is effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR). A reanalysis of patient-reported symptom data in MFNS trials was performed to determine its impact on ocular symptoms. METHODS: Ocular symptom data were pooled from 4 randomized, double-blind, placebo-controlled, phase III clinical studies (three 2-week; one 4-week); these studies followed similar protocols which compared the effectiveness of MFNS 200 mcg qd and placebo in controlling ocular symptoms in patients ≥aged 12 years with a ≥2-year history of SAR (N=983). Individual sign/symptom scores for eye tearing, itching, and redness were evaluated on a 4-point scale (0=none; 3=severe), and a total ocular symptom score (TOSS) was calculated. RESULTS: The mean baseline TOSS was 4.35 for the MFNS group and 4.5 for the placebo group. The MFNS group (n=491) showed greater decreases in TOSS than the placebo group (n=492) starting at Day 2, first reaching statistical significance at Day 3. The decrease with MFNS for the Day 1-15 interval was 19.8% vs 5.6% for placebo (P<0.001). For the same time period, the scores for tearing decreased by 22.2% with MFNS vs a decrease of 3.9% with placebo (P<0.001), for eye itching by 17.3% with MFNS vs 12.3% with placebo (P=0.002), and for redness by 15.7% with MFNS vs 8.3% with placebo (P=0.002). CONCLUSIONS: MFNS successfully reduced ocular symptoms of SAR. The effects of MFNS on these ocular symptoms are consistent with results reported with other intranasal steroids.

RATIONALE: Mometasone furoate nasal spray (MFNS) is effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR), but its efficacy in terms of controlling ocular symptoms has received less attention.METHODS: A randomized, double-blind, placebo-controlled, phase III trial evaluated the effectiveness of MFNS 200 mcg qd vs placebo in the control of SAR, including ocular signs/symptoms. The change from baseline in total ocular symptom score (TOSS) were evaluated on a 4-point scale (0=none; 3=severe).RESULTS: Patients receiving MFNS or placebo had similar baseline TOSS (mean of 3.81 for the MFNS group and 3.72 for the placebo group). For the average TOSS scores over the 15-day treatment period, the MFNS treatment group (n=104) had a 1.08-point (21.9%) decrease from baseline in TOSS, which was greater than the 0.54-point (11.6%) decrease for the placebo group (n=104) (P=0.038). The most frequently reported adverse events were headache, coughing, and pharyngitis.CONCLUSIONS: MFNS 200 mcg qd was associated with a reduction in ocular symptoms of patients with SAR. RATIONALE: Mometasone furoate nasal spray (MFNS) is effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR), but its efficacy in terms of controlling ocular symptoms has received less attention. METHODS: A randomized, double-blind, placebo-controlled, phase III trial evaluated the effectiveness of MFNS 200 mcg qd vs placebo in the control of SAR, including ocular signs/symptoms. The change from baseline in total ocular symptom score (TOSS) were evaluated on a 4-point scale (0=none; 3=severe). RESULTS: Patients receiving MFNS or placebo had similar baseline TOSS (mean of 3.81 for the MFNS group and 3.72 for the placebo group). For the average TOSS scores over the 15-day treatment period, the MFNS treatment group (n=104) had a 1.08-point (21.9%) decrease from baseline in TOSS, which was greater than the 0.54-point (11.6%) decrease for the placebo group (n=104) (P=0.038). The most frequently reported adverse events were headache, coughing, and pharyngitis. CONCLUSIONS: MFNS 200 mcg qd was associated with a reduction in ocular symptoms of patients with SAR.

We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. Current measures of cough sensitivity in the human provide no information regarding the intensity of cough. The influence of codeine on cough perceptual sensitivity and the relationship to cough intensity with capsaicin-induced cough in normal subjects has not been evaluated. This study determined the effect of codeine on capsaicin-induced cough perceptual sensitivity and motor response in normal subjects in a double-blind, placebo-con trolled, crossover study. This approach investigated the relevance of cough sensitivity, intensity, and sensory modalities in the assessment of cough suppression in humans. This study consisted of three experimental trials: administration of placebo, 30 mg codeine and 60 mg codeine.The study was double-blinded. The order of the three trials was randomized. Respiratory motor pattern was recorded with EMGs from the rectus abdominis, lateral abdominal muscles and eighth intercostal space. The subjects leaned into a fume hood to inspire deeply for 2s once through a mouthpiece connected to the nebulizer. A modified Borg scale was used to estimate their Urge-to-Cough. The experimental trial consisted of eight test solutions of 0-200 mu M capsaicin. Each solution was presented three times in a randomized block order for a total of 24 presentations. The lowest capsaicin concentration to elicit a cough was determined. The lowest capsaicin concentration to elicit an Urge-to-Cough greater than zero was identified. The Urge-to-Cough sensitivity was determined from the log-log slope.For placebo, the Urge-to-Cough was zero with inhalation of the vehicle and no coughs were observed. The threshold capsaicin concentration for subjects to report an Urge-to-Cough was 15.6 mu M (+/- 2.6 SEM). The capsaicin concentration threshold for eliciting a cough was significantly greater, 39.3 mu M (+/- 5.6 SEM). As the capsaicin concentration increased, the magnitude estimation of the Urge to-Cough increased. The slope of the log-log relationship for the Urge-to-Cough was 0.94 (+/- 0.07 SEM). As the capsaicin concentration increased, the number and intensity of the coughs increased. The administration of 30 and 60 mg codeine had no significant effect on the threshold capsaicin concentration for the Urge-to-Cough. There was also no significant codeine effect on the slope of the log-log Urgeto-Cough relationship. Thirty and sixty milligram codeine had no significant effect on the relationship between the capsaicin concentration and the number and intensity of the coughs.The results of this study demonstrate that the threshold for a subject to perceive an Urge-to-Cough was less than the capsaicin concentration that elicits the cough motor response. There Was a direct relationship between the sensory intensity (magnitude estimation of the Urge-to-Cough) and the cough number and intensity. Thus, as the sense of an Urge-to-Cough increased the cough motor response increased. Neither the 30 nor 60 mg codeine affected the perceptual or motor sensitivity to capsaicin-induced cough. These results showed that the initial threshold for responding to capsaicin-induced cough is the perception of an Urge-to-Cough, followed by a motor cough response if the capsaicin is increased above the perceptual threshold. As the capsaicin concentration increases, both the perceptual need to cough and the cough motor response increase. The response of subjects to inhalation of capsaicin consisted of both a sensory component leading to perception of an Urge-to-Cough and motor cough behavior. (c) 2007 Elsevier Ltd. All rights reserved.

The airway defensive response to tussive agents, such as capsaicin, is frequently assessed by counting the number of cough sounds, or expulsive events. This method does not identify or differentiate important respiratory events that occur in the respiratory muscles and lungs, which are critical in assessing airway defensive responses. The purpose of this study was to characterize the airway defensive behaviours (cough and expiration reflex) to capsaicin exposure in humans. We observed complex motor behaviours in response to capsaicin exposure. These behaviours were defined as cough reacceleration (CRn) and expiration reflex (ERn), where n is the number of expulsive events with and without a preceding inspiratory phase, respectively. Airway defensive responses were defined in terms of frequency (number of expulsive events), strength (activation of abdominal muscles) and behaviour type (CRn vs. ERn). Thirty-six subjects (15 females, 24+/-4 yr) were instrumented with EMG electrodes placed over the rectus abdominis (RA), external abdominal oblique (EO) and the 8th intercostal space (IC8). A custom-designed mouth pneumotachograph was used to assess the airflow acceleration, plateau velocity and phase duration of the expulsive phase. Subjects inhaled seven concentrations of capsaicin (5-200 microM) in a randomized block order. The total number of expulsive events (frequency) and the sum of integrated EMG for the IC8, RA and EO (strength) increased in a curvilinear fashion. Differentiating the airway defense responses into type demonstrated predominately CR1 and CR2 (i.e. inspiration followed by one and two expulsive events, respectively) with very few ER's at <50 microM capsaicin. At higher concentrations (>50 microM) ER's with one or more expulsive events (ER1) appeared, and the number of CR's with three or more expulsive events (CR3) increased. The decrease in EMG activation and airflow measurements with each successive expulsive event suggests a decline in power and shear force as the number of expulsive events increased. Therefore, the airway defensive response to capsaicin is a complex motor pattern that functions to coordinate ER's and CR's with differing numbers of expulsive events possibly to prevent aspirations and keep air moving to promote clearance.

RATIONALE: Mometasone furoate nasal spray (MFNS) has been shown to be effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR). Its potential efficacy for moderately severe ocular symptoms has not been reported.METHODS: In a randomized, double-blind, placebo-controlled, phase III trial comparing the effectiveness of MFNS 200 mcg qd vs placebo in the control of SAR (including ocular signs/symptoms), we analyzed patients aged 12 to 63 years with a ≥2-year history of SAR presenting with moderate-to-severe ocular signs/symptoms (baseline total ocular symptom score [TOSS] ≥4). Individual symptom scores were evaluated on a 4-point scale (0=none; 3=severe); TOSS was the sum of the 3 scores.RESULTS: Patients receiving MFNS or placebo had similar baseline TOSS (mean of 5.51 for the MFNS group and 5.63 for the placebo group). For the average TOSS over the 15-day treatment period, the MFNS treatment group (n=47) had a -1.9-point (-35.2%) change from baseline, which was significantly (P=0.038) greater than the -1.07-point (-18.5%) change for the placebo group (n=45). The most frequently reported adverse events were headache, coughing, and pharyngitis.CONCLUSIONS: MFNS 200 mcg qd was shown to be an effective treatment for patients with moderately severe ocular symptoms of SAR. RATIONALE: Mometasone furoate nasal spray (MFNS) has been shown to be effective in controlling the nasal symptoms of seasonal allergic rhinitis (SAR). Its potential efficacy for moderately severe ocular symptoms has not been reported. METHODS: In a randomized, double-blind, placebo-controlled, phase III trial comparing the effectiveness of MFNS 200 mcg qd vs placebo in the control of SAR (including ocular signs/symptoms), we analyzed patients aged 12 to 63 years with a ≥2-year history of SAR presenting with moderate-to-severe ocular signs/symptoms (baseline total ocular symptom score [TOSS] ≥4). Individual symptom scores were evaluated on a 4-point scale (0=none; 3=severe); TOSS was the sum of the 3 scores. RESULTS: Patients receiving MFNS or placebo had similar baseline TOSS (mean of 5.51 for the MFNS group and 5.63 for the placebo group). For the average TOSS over the 15-day treatment period, the MFNS treatment group (n=47) had a -1.9-point (-35.2%) change from baseline, which was significantly (P=0.038) greater than the -1.07-point (-18.5%) change for the placebo group (n=45). The most frequently reported adverse events were headache, coughing, and pharyngitis. CONCLUSIONS: MFNS 200 mcg qd was shown to be an effective treatment for patients with moderately severe ocular symptoms of SAR.

OBJECTIVE:To evaluate the efficacy and safety of mometasone furoate nasal spray (NS) for the treatment of nasal polyposis.DESIGN:Randomized, double-blind, placebo-controlled, parallel-group, multicenter study.SETTING:A total of 24 centers in 17 countries.PATIENTS:A total of 310 subjects 18 years or older with bilateral nasal polyps.INTERVENTIONS:(1) A 200-microg dose of mometasone furoate NS in the morning and matching placebo in the evening; (2) 200-microg doses of mometasone furoate NS in the morning and evening; or (3) matching placebo in the morning and evening. All 3 regimens were administered as a nasal spray for 4 months.MAIN OUTCOME MEASURES:Primary end points were change from baseline to last assessment in physician-assessed bilateral polyp grade and change from baseline in subject-assessed congestion and/or obstruction score averaged over the first month of treatment. Analysis of variance was used for all efficacy end points except for change in bilateral polyp grade, for which baseline polyp grade was added as a covariate to the analysis of variance model to account for any between-group baseline differences in this variable.RESULTS:Mometasone furoate NS doses of 200 microg administered once or twice daily produced greater reductions in bilateral polyp grade at the end point than placebo, with differences reaching statistical significance with twice-daily dosing (P = .04). Over 1 month, both mometasone furoate NS regimens produced statistically superior improvements from baseline in congestion and/or obstruction score vs placebo (P = .01 for once-daily dosing; P<.001 for twice-daily dosing). The drug was well tolerated.CONCLUSION:Mometasone furoate NS is an effective and well-tolerated treatment for bilateral nasal polyposis in adults, reducing nasal polyp size and symptoms of nasal congestion and/or obstruction.

Background: Studies have suggested that topical corticosteroids are effective in the treatment of nasal polyps; however, this has yet to be confirmed in a large, robust clinical trial.Objective: To evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) for nasal polyposis.Methods: A total of 354 subjects with bilateral nasal polyps and clinically significant congestion/obstruction participated in this multinational, randomized, double-blind, placebo-controlled study. Subjects received MFNS 200 mu g once or twice daily or placebo for 4 months. Coprimary endpoints were (1) change from baseline to last assessment in physician-evaluated bilateral polyp grade score and (2) change from baseline averaged over month 1 in subject-assessed nasal congestion/obstruction. ANOVA was used for all efficacy endpoints, except for change in bilateral polyp grade score, for which baseline polyp grade was added as a covariate.Results: Compared with placebo, MFNS 200 mu g administered once or twice daily produced significantly greater reductions in bilateral polyp grade score (P <.001, P =.010, respectively) and congestion/obstruction (P =.001, P <.001), as well as improvement in loss of smell (P <.001, P =.036), anterior rhinorrhea (P <.001 for both), and postnasal drip (P <.001, P =.001) over month 1. MFNS 200 mu g twice daily was superior to MFNS 200 jig once daily in reducing congestion/obstruction (P =.039), and there were more improvers in the MFNS 200 mu g twice daily group (P =.035). MFNS was well tolerated in both groups.Conclusion: MFNS 200 mu g, once or twice daily, was safe and significantly superior to placebo in reducing polyp grade (size and extent) and improving congestion/obstruction and return of sense of smell. MFNS is an effective medical treatment for nasal polyposis and may reduce or delay the need for surgery.

Background: Cough is a frequent complaint of patients with a variety of respiratory disorders, including seasonal allergic rhinitis (SAR), and it is often evaluated subjectively to determine disease status and response to treatment. However, it is not known whether subjective reports of cough from patients with SAR are accurate.Objective: To compare a novel objective measurement with subjective reports of cough frequency in a subset of 28 patients (aged greater than or equal to12 years) with active SAR who were enrolled in a large, multicenter trial examining the efficacy of an active treatment for SAR.Methods: In this supplemental pilot study, subjective data were collected on a diary card and objective data were collected using home-based telemetry. Three 24-hour recording sessions were conducted with each patient: 2 consecutive baseline sessions (day 1 and day 2) and 1 session after randomization to placebo or active cough treatment (day 3).Results: Strong correlations existed between cough frequency data for days 1 and 2 (Spearman correlation coefficient = 0.91; P <.001) and between subjective and objective data for days 1, 2, and 3 (daytime greater than nighttime) (Spearman correlation coefficient = 0.51; P <.001).Conclusion: These results have implications for the design and interpretation of results from clinical trials that evaluate cough frequency as a treatment outcome.

Background: Asthma and seasonal allergic rhinitis (SAR) are recognized as manifestations of a single airway disease. Desloratadine has demonstrated efficacy in treating SAR symptoms, including nasal obstruction. Methods: Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind, placebo-controlled trial of patients with SAR and symptoms of asthma, who were assigned randomly to once-daily treatment with desloratadine 5 mg, montelukast 10 mg, or placebo for 4 weeks. Change from baseline of AM/PM reflective total asthma symptom severity scores (TASS), FEV1, individual asthma symptom scores, and β2-agonist usage were assessed. Results: Desloratadine and montelukast each were associated with statistically significant reductions from baseline in the mean TASS averaged over the 4-week period (p ≤0.022 vs. placebo). Individual asthma symptom scores also improved significantly for both therapies (p ≤ 0.05). Patients treated with desloratadine or montelukast demonstrated improvement from baseline in FEV1 versus placebo; significant improvement was seen in a subset of patients with baseline FEV1 <80% of predicted normal (both p < 0.05). Both active therapies significantly reduced β2-agonist use (both p < 0.01). Improvements for both therapies were comparable for all efficacy parameters; they were tolerated well with adverse event profiles similar to placebo. Conclusions: Asthma symptoms and β2-agonist were improved significantly in patients with concomitant SAR and asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily. Both therapies significantly improved FEV1 in a subset of patients with FEV1 <80% of predicted normal at entry. Improvements in asthma symptoms were comparable for both active treatment groups.

Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.

New-generation H1-blockers may possess antiallergic properties, and their effect may differ, depending on the target organ. A double-blind, placebo-controlled, parallel-group study was carried out during the pollen season to compare the clinical effect on nasal and conjunctival symptoms of astemizole (10 mg o.d.) and loratadine (10 mg o.d.) with their effect on skin-test reactivity to allergen and histamine. Thirty-eight patients (12-56 years of age) were studied. Nasal and ocular symptoms were recorded daily from days 4 to 7. Skin prick tests with serial concentrations of allergens and one concentration of histamine were carried out before and at the end of the 7-day treatment period. Parallel-line bioassay, analysis of variance, and covariance were used to analyze skin test data. Loratadine and astemizole significantly decreased symptoms from baseline (P < 0.004 and P < 0.006). Skin-test reactivity to allergen and histamine was more profoundly decreased by astemizole than loratadine. The histamine covariant was more important in the allergen effect of astemizole than in that of loratadine. Two H1-blockers having the same clinical effect on nasal and ocular symptoms during the pollen season have totally different effects on skin-test reactivity. Skin-test reactivity to allergen or histamine is not predictive of the clinical efficacy of H1-blockers during seasonal allergic rhinitis.

Background The aim of this study was to evaluate the in vivo and ex vivo effects of the H.‐antagonist loratadine on histamine release. Methods The study was designed as a double‐blind, crossover trial. Ten patients with allergic rhinitis due to Dermatophagoides pteronyssinus were treated with loratadine (10 mg daily p.o.) and with placebo for 1 week, with a 2‐week interval between the two treatments. Nasal lavages with saline solution were done before and after challenge with the relevant allergen at the end of treatments with loratadine and placebo. Venous blood was taken after treatments, and basophil histamine release induced by anti‐IgE (10 μg/ml), N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP, 1 μM). and Ca2+ ionophore A23187 (1 μM) was evaluated by ati automated fluorometric method. Results Treatment with loratadine attenuated early antigen‐tnduced nasal obstruction, rhinorrhea. and itching. Nasal symptoms were accompanied by a significant histamine release in the nasal lavages collected 5 min after stimulation when the patients received placebo (median 4 ng/ml, range 1‐28; P<0.05). After treatment with loratadine, histamine release in the 5‐min postchallenge lavages was almost abrogated (median 0.5 ng/ml, range 0‐3; P<0.01 vs placebo). Median anti‐IgE‐induced histamine release from basophils was 41.9% (range 27.8‐79.2) after placebo and 30.0% (range 1.7‐73.3, P < 0.05) after loratadine. Active treatment exerted an inhibitory effect also on basophil histamine release induced by fMLP and Ca2+ ionophore A23187. Conclusions Treatment for 1 week with loratadine reduces allergen‐mduced nasal symptoms and inhibits in vivo and ex vivo histamine release in patients with allergic rhinitis.

IL-5 is a prominent and perhaps an essential element in the induction of allergic inflammation in human asthma and other allergic diseases. Despite the strong biochemical and clinical correlates between lung eosinophilia and asthma, there is no clear understanding of how eosinophils exacerbate asthma. Antigen administration to sensitized animals produces eosinophilic infiltration that is very similar to that in man, and is prevented by administration of a neutralizing monoclonal antibody against IL-5. Mice in which the IL-5 gene is absent are unable to mount eosinophilic responses to antigen and do not sustain lung damage, but otherwise develop normally. The study of the biology of IL-5 has not only clarified the links between eosinophilia and airway hyperreactivity, but also strongly suggests that anti-IL-5 therapy may be an effective, safe, and novel way of treating human asthma and perhaps other eosinophilic diseases. There are many different potential approaches to the inhibition of IL-5, but the one most likely to provide "proof of principle" in "asthma in the wild" in man is a monoclonal antibody against IL-5.