Intermittent Allergic Asthma Research Articles

Evaluation of Bronchial Hyperreactivity with Mannitol Dry Powder Challenge Test in a Paediatric Population with Intermittent Allergic Asthma or Allergic Rhinitis

We evaluated the bronchial hyperreactivity (BHR) with a new bronchial challenge test, mannitol dry powder, in a paediatric population with intermittent allergic asthma or allergic rhinitis who did not respond to an exercise challenge test. We selected 50 children, aged 9-16 years, with intermittent allergic bronchial asthma (Group 1) or allergic rhinitis without clinical manifestation of asthma for at least 12 months (Group 2). All patients performed the following tests in three different days (≥ 48 hours apart): Day 1: exhaled nitric oxide (FeNO) determination followed by baseline spirometry and reversibility to inhaled beta2-agonists; Day 2: exercise challenge test followed by FeNO determination; Day 3: mannitol challenge test followed by FeNO determination. Forty children completed the study. Eighteen subjects of Group 1 (90 percent) and 5 subjects of Group 2 (25 percent) resulted positive to the mannitol test. Positive mannitol challenge subjects showed no statistically significant differences compared to negative subjects as regard baseline spirometry, reversibility to salbutamol and response to the exercise challenge test, but they had significantly higher FeNO values. In conclusion, the mannitol challenge test can be a diagnostic tool more useful than the exercise challenge test to identify BHR in a paediatric population with intermittent allergic asthma or allergic rhinitis because it is better reproducible, quick and easy to perform and well tolerated.

Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma

Allergic asthma is IgE-mediated and the IgE-sensitisation is usually demonstrated by skin prick tests (SPT) and IgE antibody determinations in serum. The SPT and IgE-antibody values do not directly predict if the allergy clinically contributes to the asthma. There is therefore a need for new objective tests that may indicate the clinical importance of an IgE-sensitisation. To evaluate basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in allergic asthma. Twenty-six subjects with stable, intermittent allergic asthma were tested with SPT and spirometry, and methacholine and allergen inhalation challenges to determine methacholine PD(20) (provocative dose causing a 20% drop in forced expiratory volume in 1 s) and allergen PD(20) . The results were compared with CD-sens and serological parameters, i.e. IgE- and IgG4 antibodies to the relevant allergens. A significant correlation was found between CD-sens and allergen PD(20) (P = 0.01; r = 0.49; n = 26) as well as between CD-sens and the ratio of allergen PD(20) to methacholine PD(20) (P = 0.007; r = 0.52; n = 26). In patients with a moderate to low degree of bronchial hyperresponsiveness there was an excellent correlation (P = 0.0001; r = 0.88, n = 13) between CD-sens and allergen sensitivity. No relation to either allergen PD(20) or the ratio was found for basophil allergen reactivity measured as CD63 up-regulation at high concentrations of the respective allergen. CD-sens was found to be an objective marker of airway allergen sensitivity in stable allergic asthmatics, that may be used to predict airway responsiveness when bronchial challenge tests cannot be performed.

Segmental allergen challenge alters multimeric structure and function of surfactant protein D in humans.

Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.

Oxidative stress and airway inflammation after allergen challenge evaluated by exhaled breath condensate analysis

Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane. The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2) ) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen. At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P<0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P<0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P<0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.85, P<0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.52, P=0.001). The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma.

Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure. In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 microg Turbuhaler, budesonide 160 microg/formoterol 4.5 microg Turbuhaler and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD(20)), exhaled nitric oxide fraction (F(eNO)), sputum eosinophils and prostaglandin D(2), and diary card recordings of symptoms (on a scale of 0-10), short-acting beta(2)-agonist use and evening forced expiratory volume in one second (FEV(1)). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD(20): 397 (98) microg before versus 168 (82) microg after), F(eNO) (mean+/-sd 46+/-31 ppb before versus 73+/-46 ppb after) and asthma symptom score (mean+/-sd 0.39+/-0.55 before versus 0.68+/-0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV(1). Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation. Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.

Body mass index, respiratory function and bronchial hyperreactivity in allergic rhinitis and asthma

Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. The aim of the study was to analyse the relationship between BMI and allergic diseases, including allergic rhinitis and asthma, and functional parameters, such as nasal airflow, FEV(1), and non-specific BHR to methacholine, in a cohort of navy army subjects. The study included 100 patients with moderate-severe persistent allergic rhinitis alone, 100 with intermittent allergic asthma alone, and 100 healthy controls. All subjects were evaluated performing skin prick test, spirometry, and bronchostimulation test with methacholine. Rhinomanometry was performed in patients with rhinitis. BMI values were significantly lower in control subjects with respect to patients with rhinitis (P=0.0002) and with respect to patients with asthma (P<0.0001). BMI was also significantly higher in males with respect to females (P=0.005). A significant relationship has been observed between some categories of BHR and BMI either in patients with rhinitis (P<0.01) or in patients with asthma (P<0.01), whereas there was no association between BMI and functional parameters. This study provides the first evidence of a significant relationship between BMI and allergic rhinitis and between BMI and BHR in both allergic disorders.

Minimal tolerance to the bronchoprotective effect of inhaled salmeterol/fluticasone combination on allergene challenge

In order to assess whether the administration of salmeterol/fluticasone propionate combination (50/250 mcg by Diskus) for 1 week induces tolerance to the bronchoprotective effect of salmeterol on allergen challenge, a single-blind, cross-over study was carried out. We studied nine subjects (eight men and one woman; mean age±SD: 31.3±11.0 yr) with mild intermittent allergic asthma, never treated with regular beta2-agonists or inhaled corticosteroids. In a previous allergen challenge all subjects had shown a positive early airway response (EAR) to allergen. They underwent allergen challenge after 1-week treatment with placebo and a single dose of placebo immediately before allergen challenge (T1), or 1-week treatment with placebo and a single dose of salmeterol/fluticasone immediately before allergen challenge (T2), or 1-week treatment with salmeterol/fluticasone combination bid and a single dose of salmeterol/fluticasone immediately before allergen challenge (T3). EAR was evaluated both as maximum decrease in FEV 1 (MaxΔFEV 1%) after allergen challenge and as area under FEV 1-time curve. MaxΔFEV 1% during allergen challenge protected by placebo (T1) was significantly greater than MaxΔFEV 1% during allergen challenges protected by single dose of salmeterol/fluticasone (T2) and by salmeterol/fluticasone 1-week treatment (T3). No difference was found in MaxΔFEV 1% between T2 and T3. The same results were observed also after computing the area under the curve for each challenge. When individually considered, all subjects were protected against EAR (protection index ⩾80%) at T2, while at 3 seven out of nine subjects were still protected against EAR. In conclusion, the simultaneous administration of salmeterol and fluticasone in the same device prevents in almost 80% of examined subjects the development of tolerance to the protective effect of salmeterol on allergen challenge. This observation may contribute to explain the positive interaction between inhaled beta2-agonists and corticosteroids in the long-term treatment of asthma.

Allergy to turnip greens

Rationale Turnip greens are the leaves of turnip ( Brassica napus), commonly eaten cooked in North-Western Spain. We present a 38-year-old-female patient with history of allergic rhinoconjunctivitis and mild intermittent allergic asthma, sensitized to grass, plantain and tree's pollen, who referred contact urticaria and rhinitis when handling and cutting turnip greens, but no symptoms when cooking or eating them. Methods We performed prick-by-prick with raw and cooked turnip greens, using negative (buffered physiologic saline) and positive (histamine) controls. We performed an open challenge by making the patient handle and cut the turnip greens. We measured specific IgE (EAST) and Western blotting (SDS-PAGE Immunoblotting) with and without 2-mercaptoethanol. Results Prick-by-prick with raw vegetable resulted on a 7 mm diameter wheal, greater than Histamine (4 mm). Was negative with the cooked vegetable. Negative control was also negative. Challenge was positive with skin eruption and rhinoconjunctivitis without spyrometric changes. Specific IgE was positive (class 1) for turnip greens, cabbage, cauliflower, celery and Brussel's sprout, negative (class 0) for broccoli and rape-seed. We could not detect any specific IgE fixing band on the turnip greens' extract on the Western blotting Conclusions Our patient presents immediate contact allergy to turnip greens, probably in relation with thermolabile allergens and in relation with crossreactivity with the primary sensitization to grass, plantain and trees' pollen.

Steroid-Naive Adolescents with Mild Intermittent Allergic Asthma Have Airway Hyperresponsiveness and Elevated Exhaled Nitric Oxide Levels

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25–75%, and FVC values not significantly different from controls, (p>0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 ≥ 400 µg or accumulative dose ≤1220 µg) and moderate in 32.7% (MCh PD20 400–1400 µg or accumulative dose 1220–4620 µg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 ± 5.3 ppb and 4.4 ± 0.7 ppb, respectively; p<0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., >2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25–75% values and MCh PD20 (r = 0.358; p<0.01) or MCh accumulative dose (r = 0.355; p<0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p>0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.

Tolerance to the Protective Effect of Salmeterol on Allergen Challenge Can Be Partially Restored by the Withdrawal of Salmeterol Regular Treatment

To assess whether the withdrawal of salmeterol treatment for 3 days (72 h) can restore its bronchoprotective ability on specific bronchial provocative test (sBPT) with allergen, which was completely lost after 1 week of regular treatment with salmeterol. Single-blind design. We investigated 10 nonsmoking subjects (8 men and 2 women; mean +/- SD age, 24 +/- 8 years) with mild intermittent allergic asthma in the stable phase of the disease, who were never previously treated with regular beta(2)-agonists. Subjects with a previous positive early airway response (EAR) to a screening allergen challenge were considered. They underwent sBPT with allergen after a single dose of inhaled salmeterol, 50 microg (T(1)), and then underwent sBPT after 1 week of regular treatment with inhaled salmeterol, 50 microg bid (T(2)); after that, they continued inhaled salmeterol treatment for 4 days, and then changed to inhaled salmeterol with placebo (two puffs bid) for 3 days (72 h) and underwent sBPT with allergen after a single dose of salmeterol, 50 microg (T(3)). EAR to allergen (DeltaFEV(1) > or = 20% with respect to postdiluent value) was completely abolished by a single dose of salmeterol (T(1); protection index [PI] > or = 50% in all subjects), but it was still present after 1 week of regular treatment with salmeterol (T(2); PI < 50% in all subjects). The maximum FEV(1) percentage fall during sBPT with allergen was significantly lower after withdrawal of regular inhaled salmeterol (T(3)) than after regular treatment with salmeterol (T(2)) (mean, 23% vs 29.5%; range, 4 to 41% vs 18 to 49%, respectively; p < 0.05); a similar result was obtained considering the PI of salmeterol on sBPT with allergen (mean, 44% vs 20%; range, 2 to 86% vs - 11 to 49%, respectively; p < 0.05). However, the maximum FEV(1) percentage fall and PI were significantly different in T(3) than after T(1), and only 4 of 10 patients showed in T(3) a PI > or = 50%. The bronchoprotective effect of salmeterol on allergen-induced EAR, completely lost after 1 week of regular treatment with salmeterol, may be partially restored by the withdrawal of salmeterol therapy for 3 days (72 h). However, this withdrawal time period is not sufficient to recover the baseline bronchoprotective efficacy of the first dose of salmeterol.