Air pollution and seasonal asthma during the pollen season. A cohort study in Puertollano and Ciudad Real (Spain)

BACKGROUND: Many studies have demonstrated a positive association between air pollutants and emergency visits for asthma. However, few studies have included pollen when analysing this relationship in mild-moderate asthmatic patients. OBJECTIVE: To determine the importance of the pollutants such as ozone (O(3)), particles (PM(10)), nitrogen dioxide (NO(2)) and sulphur dioxide (SO(2)) in the clinical course of mild-moderate pollen-allergic asthmatic patients from two Spanish towns in La Mancha: Puertollano (high pollution levels) and Ciudad Real (low pollution levels). METHODS: We used a Poisson regression model to study a cohort of 137 patients from Puertollano and Ciudad Real during two pollen seasons (2000-2001) and analysed the relationship between air pollutant and pollen levels and daily symptoms, the medication used and peak-flow measurements. RESULTS: The number of asthma symptoms and the mean values of the PM(10), SO(2) and NO(2) levels were higher in Puertollano than in Ciudad Real. In Puertollano, the risk of asthma increased by 6% with a 3-day lag for PM(10), by 8% with a 3-day lag for O(3), by 4% with a 1-day lag for SO(2) and by 15% with a 3-day lag for O(3) when its values exceeded the health threshold (P < 0.05). CONCLUSIONS: The air pollution levels in Puertollano were associated with an increased risk of asthma symptoms in pollen-allergic asthmatic patients com pared with a similar group from Ciudad Real.     

Peach allergy pattern: experience in 70 patients

We report the clinical characteristics of peach allergy encountered in a population of peach-allergic patients. We evaluated 165 patients. The 70 peach-allergic patients were diagnosed through clinical history, the skin prick-prick test, and open oral challenge and rub tests to peach. As a pollinic control group. 95 pollen-allergic patients were also evaluated. Some 49% of the patients were male and 51% female. The mean age was 20±8 years. Oral allergy syndrome (86%) was the most common symptom, followed by contact urticaria (61%) and systemic symptoms (26%). Some 67% of the patients were allergic to peach pulp, and 36% reported symptoms related to canned peach. Canned peach and pulp symptoms were statistically associated (P<0.01), and symptoms to canned peach were more frequently reported by patients with systemic symptoms (f <0.05). On evaluation of the peach-allergic patients" characteristics, three risk factors - allergy to peach pulp, allergy to canned peach, and peach allergy in non-pollen-allergic patients - were found, indicating development of systemic symptoms on eating peach. Most of the peach-allergic patients (81%) also had pollen allergy, which was linked to a higher prevalence of asthma (73%) than in the pollen-allergic patients of the control group (48%): this difference was statistically significant (f <0.01). Finally, two groups were clearly defined by the seriousness of the peach allergy - the non-pollen-allergic patients were more predisposed to the occurrence of systemic symptoms (>50%), and the pollen-allergic patients to asthma (>70%).     

Vine pollen allergy in areas with a high density of vineyards.

BACKGROUND: In Castilla-La Mancha, Spain, the area with the highest density of vineyards in the world, 2 cases of Vitis vinifera pollen allergy have been previously reported. OBJECTIVE: To determine the clinical relevance and biochemical characteristics of vine pollen in the Spanish province of Ciudad Real. METHODS: We designed a prospective study of patients treated in the allergy units from Puertollano and Ciudad Real for respiratory symptoms of 4 months' duration in the year 2000. Skin prick tests with a standard aeroallergen battery and V vinifera pollen extract were performed on all patients. We also performed conjunctival and bronchial provocation tests and serum specific IgE and sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting on the patients who tested positive for V vinifera pollen. RESULTS: We included 200 patients, 98 sensitized to any pollen and 9 to V vinifera pollen. We found 8 of 9 positive conjunctival provocation test results and a positive bronchial provocation result to vine pollen in a vine grower. Serum specific IgE against V vinifera pollen was detected in 9 of 9 patients. Immunoblotting with V vinifera pollen extract showed IgE-binding bands at 45 and 67 kDa. CONCLUSIONS: Vine pollen could be the cause of pollinosis in exposed patients living in areas with a high density of vineyards.     

Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children

BACKGROUND: Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well-tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose-response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma. METHODS: Eighty-eight children (5-15 years) with a history of tree pollen-induced allergic rhinoconjunctivitis with/without seasonal asthma for >or=2 years were included. Allergy to tree pollen was confirmed by positive skin-prick test, positive specific IgE and positive conjunctival provocation test. The extract used was a glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100,000 SQ-U/ml. Children were randomized into three groups receiving SLIT 5 days a week for up to 18 months; dose group 1: accumulated weekly dose of 24,000 SQ-U; dose group 2: accumulated weekly dose of 200,000 SQ-U; and placebo. RESULTS: In the birch pollen season, dose group 2 showed a significant reduction of symptom (P = 0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed a significant reduction of symptom scores (P = 0.03). There were no statistical differences between dose groups 1 and 2. All children tolerated the treatment well. CONCLUSION: SLIT with tree pollen extract provided dose-dependent benefits in tree pollen-allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.     

Peak-flow variability in asthmatic children is not related to wall-to-wall carpeting on classroom floors

The hypothesis was tested that wall-to-wall carpets on school classroom floors have a negative effect on the respiratory health of asthmatic children. Asthmatic patients ( n = 98) were selected from the records of the Sophia Children's Hospital in Rotterdam. The patients were between 5 and 11 years old. All children had peak-flow measurements three times a day for a 1-month period. The parents of the children completed a diary in which respiratory symptoms and medication use were recorded daily for the same period. Dust samples were taken from classroom floors, living-room and bedroom floors, and mattresses of the children. The dust samples were analyzed for Der p I content, the major allergen of the house-dust mite Dermatophagoides pteronyssinus. The results of the study showed that there was no significant difference between children visiting schools with or without carpeted classroom floors in peak-flow variability, acute respiratory symptoms, or medication use. The Der p I content of dust collected from classroom floors was much lower than of dust collected from homes. There was a significant correlation between peak-flow variability and mattress dust Der p I content in asthmatic children sensitized to dust mites, but not between peak-flow variability and classroom floor dust Der p I content. We concluded that carpeted classroom floors do not contribute to asthma symptom severity, possibly because of the low levels of Der p I on them.     

Psychological morbidity and coping skills in patients with brittle and non-brittle asthma: a case-control study

Background An association between psychological morbidity and asthma is well recognized and an increase in negative psychosocial factors in brittle asthma has been previously reported. Stich factors, apart from affecting patient perceptions, may alter patients’ self-management of their condition. Methods We have undertaken a case-control study on 29 well characterized brittle and non-brittle asthmatics in the West Midlands Region to assess their level of psychological morbidity, using the General Health Questionnaire (GHQ) and the living with asthma questionnaire, and their responses to changes in asthma symptoms, using the Asthma Symptom Checklist and a taped interview. Results Significant differences in GHQ (mean score brittle 19.5 vs non-brittle 7.2, P = 0.0002) and living with asthma (mean score brittle 1.30 vs non-brittle 1.00, P = 0.002) reinforced the presence of psychological factors in this group of patients with severe asthma. Interviews regarding responses to hypothetical asthma attacks showed that patients with brittle asthma delayed seeking medical attention more often than those with non-brittle asthma and instead preferred to self-administer beta-agonist medication. Sixteen (55.2%) of the 29 patients with brittle asthma would have delayed 7 days before seeking medical attention in a slow onset attack compared with 6/29 (20.7%) in the non-brittle group. In a fast onset attack 14 (48.3%) patients with brittle asthma would not have summoned help, despite finding it difficult to walk to the kitchen for a drink whereas in the non-brittle group 24 out of 29 (82.8%) would have summoned help. Levels of family support tended to be lower in patients with brittle asthma (mean family APGAR 7.3 vs 8.65 P = 0.09). Conclusions Brittle asthma is associated with greater psychological morbidity and altered strategies for coping with deteriorating asthma symptoms. Attention should be paid to the presence of such factors in the management of patients with brittle asthma.     

Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis

BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc. RESULTS: Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.     

Factors associated with severity of occupational asthma with a latency period at diagnosis

BACKGROUND: Severity of occupational asthma at diagnosis is an important prognostic factor. The aim of this study was to determine which factors affect the severity of occupational asthma with a latency period at diagnosis. METHODS: The study population consisted of 229 consecutive subjects with occupational asthma with a latency period recruited by four occupational health departments and divided into two groups according to the severity of the disease at diagnosis. The moderate-severe (FEV(1) <70% predicted, or PD(20) methacholine /=70% predicted and PD(20) methacholine >300 microg, n = 128) groups were compared in terms of clinical and demographic parameters. Multivariate analysis using logistic regressions was performed to examine factors associated with asthma severity. RESULTS: Duration of symptoms before diagnosis was significantly longer in the moderate-severe group (mean +/- SD: 6.3 +/- 6.8 years vs 3.4 +/- 4.4 years, P < 0.001). Sex ratio, age, atopy, smoking habits, duration of exposure before symptoms, and molecular weight of the causal agent were not significantly different between the two groups. On multivariate analysis, only duration of symptoms before diagnosis was associated with asthma severity (aOR = 1.12, 95% CI 1.05-1.18, P < 0.001). CONCLUSIONS: Severity of occupational asthma with a latency period at diagnosis was associated with duration of symptoms before diagnosis, but not with the type of causal agent. This finding emphasizes the need for early diagnosis and avoidance of exposure.     

Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study

BACKGROUND: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite-induced respiratory allergy. METHODS: Twenty-four patients (age range 8-15 years), suffering from mild to moderate asthma, with single sensitization to mite allergen, were enrolled. After a 1-year observation phase, patients were randomly allocated to one of two groups, and were given SLIT (sublingual-spit) as drops for 2 years according to a double-blind, placebo-controlled (DBPC) design. Symptoms/medication scores (diary card), visual analog scale, and immunologic parameters (house-dust-mite [HDM]-specific IgE, and total HDM-specific IgG and IgG4) were determined during the observation phase and during the DBPC treatment period. RESULTS: Twenty-one patients completed the study. At the beginning of the treatment, no difference in environmental allergenic pressure could be shown between the groups. After 2 years of therapy, there was a significant decrease in asthmatic symptoms (P=0.0001) and medication use (P=0.0001) in the active group compared to the placebo group. The visual analog score on overall asthma symptoms improved in the SLIT group (P=0.0001), but not in the placebo group. Nevertheless, the immunologic results did not show significant differences in HDM-specific IgE and total HDM-specific IgG or IgG4 between the active and placebo groups (P = NS). No relevant side-effects were recorded throughout the study. CONCLUSIONS: Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.     

Determinants of increased exhaled nitric oxide in patients with suspected asthma

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.     

Clinical pharmacology of H1-antihistamines in the skin

BACKGROUND: Birch pollen is a common allergen in northern, central, and eastern Europe. Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal. Long-term, placebo-controlled studies with subcutaneously administered standardized birch pollen extract are lacking. OBJECTIVE: The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen-allergic patients in a double-blind, placebo-controlled trial. METHODS: Forty-nine patients with histories of birch pollen allergy from the upper and lower airways, positive skin prick test and conjunctival provocation test results, and in vitro specific IgE to birch pollen (Betula verrucosa ) extract were included. Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind, randomized, placebo-controlled study. Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season. RESULTS: Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study. The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and 2.1 and 4.3, respectively, in the placebo group. The differences between the groups were significant (P =.05 in 1997 and P =.005 in 1998). The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group (P =.004 for 1997 and P =.004 for 1998). CONCLUSION: Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen-allergic patients during the pollen season.     

Time trends in asthma and wheeze in Swedish children 1996–2006: prevalence and risk factors by sex

Background:  Recent data suggest that the previously rising trend in childhood wheezing symptoms has plateaued in some regions. We sought to investigate sex-specific trends in wheeze, asthma, allergic conditions, allergic sensitization and risk factors for wheeze.
Methods:  We compared two population-based cohorts of 7 to 8-year olds from the same Swedish towns in 1996 and 2006 using parental expanded ISAAC questionnaires. In 1996, 3430 (97%) and in 2006, 2585 (96%) questionnaires were completed. A subset was skin prick tested: in 1996, 2148 (88%) and in 2006, 1700 (90%) children participated.
Results:  No significant change in the prevalence of current wheeze ( P  = 0.13), allergic rhinitis ( P  = 0.18) or eczema ( P  = 0.22) was found despite an increase in allergic sensitization (20.6–29.9%, P  < 0.01). In boys, however, the prevalence of current wheeze (12.9–16.4%, P  < 0.01), physician-diagnosed asthma (7.1–9.3%, P  = 0.03) and asthma medication use increased. In girls the prevalence of current symptoms and conditions tended to decrease. The prevalence of all studied risk factors for wheeze and asthma increased in boys relative to girls from 1996 to 2006, thus increasing the boy-to-girl prevalence ratio in risk factors.
Conclusions:  The previously reported increase in current wheezing indices has plateaued in Sweden. Due to increased diagnostic activity, physician diagnoses continue to increase. Time trends in wheezing symptoms differed between boys and girls, and current wheeze increased in boys. This was seemingly explained by the observed increases in the prevalence of risk factors for asthma in boys compared with girls. In contrast to the current symptoms of wheeze, rhinitis or eczema, the prevalence of allergic sensitization increased considerably.     

Determinants of undiagnosed asthma

BACKGROUND: The conformity between asthma diagnosed in a clinical setting and asthma from an epidemiological point of view has not been much studied. METHODS: History, symptoms, and clinical findings in persons with and without a previous physician diagnosed asthma were studied among persons classified as having asthma according to an epidemiological definition. RESULTS: Smoking was more prevalent in persons not diagnosed as having asthma prior to the study (n = 96), than in those with a previous asthma diagnosis (n = 119), (60% vs. 41%, P = 0.006). Positive skin prick test (SPT) was less common (39.6% vs. 58.0%, P = 0.009), lung function expressed as FEV1.0 in percentage of predicted was better (92.1 vs. 85.4, P = 0.018), reversibility to a bronchodilator was smaller (mean reversibility 4.0% vs. 6.2% of predicted, P = 0.003) and symptoms were less frequently reported (P < 0.001) by those who had not a physician diagnosed asthma prior to the study. CONCLUSION: The asthma diagnosis is often overlooked by the medical profession in patients with mild disease. Furthermore, smoking seems to worsen asthma exacerbations in patients with mild disease.     

心理干预辅助治疗儿童哮喘疗效观察

目的：探讨放松训练、家庭应对措施指导、认知和实践脱敏治疗等心理干预对治疗儿童哮喘的临床疗效。方法：采用随机对照方法，对诊断为儿童哮喘，符合纳入标准的116例患儿分为治疗组60人，对照组56人，给予同样药物治疗，治疗组同时进行心理干预，治疗前后观察两组临床疗效、日夜间症状记分及呼气峰流速（PEF）等。结果：治疗组在临床疗效、日间症状记分、PEF等方面均优于对照组（P＜0．05－0．01）。结论：药物辅以心理干预治疗儿童哮喘疗效优于单纯药物治疗。     

Are risk factors of childhood asthma predicting disease persistence in early adulthood different in the developing world?

BACKGROUND: Predictive factors of childhood asthma for favorable prognosis may differ between populations where a variety of genetic and environmental factors are present. OBJECTIVES: To document the factors predicting disease persistence in early adulthood in Turkey. METHODS: An outpatient cohort (n = 115) with a mean follow-up duration of 11.4 +/- 0.2 years was evaluated. Complete remission was defined as no asthma symptoms, no use of controller medication, no airflow limitation and no airway hyper-responsiveness, and clinical remission as no symptoms and no use of controller medication, within the past year. RESULTS: The mean ages during referral and at the final visit were 5.8 +/- 0.2 and 17.1 +/- 0.2 years, respectively. Thirty-one (27%) were in complete remission, and a further 30 (26%) in clinical remission. In multivariate logistic models, diminished airflow [forced expiratory volume in 1 s (FEV1) < 80% vs > or = 80%] at the initial lung function test predicted current diminished airflow (8.422; 2.202-32.206) (odds ratio; 95% confidence interval), and presence of obstructive pattern (FEV1/forced vital capacity (FVC) < 80% vs > or = 80%) predicted current obstructive pattern (29.333; 3.022-284.724). Furthermore, female gender appeared to predict persistence of asthma symptoms (3.330; 1.250-8.333) and absence of clinical remission (2.398; 1.038-5.254); eosinophilia predicted persistence of symptoms (4.271; 1.080-16.889) and presence of airway hyper-responsiveness (3.723; 1.129-12.278). CONCLUSIONS: Diminished airflow, female gender and eosinophilia appear to predict an adverse outcome of childhood asthma, supporting the concept that variability may exist between populations.     

The role of patient training in the management of seasonal rhinitis and asthma: clinical implications

BACKGROUND: Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms. METHODS: One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season. RESULTS: The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02). CONCLUSIONS: Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.     

Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, olacebo-controlled trial of a standardized five-grass-pollen extract in rhinitis

Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized grass-pollen extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the grass-pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the pollen season ( P <0.02). Moreover, at the peak of the pollen season, betamethasone consumption was significantly reduced in the SLIT group ( P <0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group ( P <0.02). IgG4 levels increased significantly in the SLIT group ( P <0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.     

Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma

BACKGROUND: Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma. METHODS: After a run-in period when an optimized fluticasone dose (> or =1000 microg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed. RESULTS: Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a > or =50% dose reduction (P=0.001). Fluticasone dose reduction to < or =500 microg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo. CONCLUSION: Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.     

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.     

The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy

BACKGROUND: Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies. AIM: To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors. METHODS: The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean). RESULTS: Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P < 0.001), higher annual mean temperature (16.2 degrees C vs. 12.9 degrees C), lower temperature range (16.0 C degrees vs. 22.1 degrees C) and lower NO2 levels (31.46 microg/m3 vs. 57.99 microg/m3) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 microg/m3 in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28). CONCLUSION: Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.