Provocative Dose Research Articles

Expiratory flows and airway inflammation in elderly asthmatic patients

Asthma in the elderly is often underrecognized and suboptimally treated, resulting in an increased morbidity and mortality. The characteristics of asthma-related bronchitis and its optimal treatment remain to be determined in this population. We aimed to compare lung function and airway inflammation in elderly and younger asthmatic subjects. Data from two induced sputum databases were analyzed in three groups of asthmatic subjects (18-30 y, n = 136; 31-59 y, n = 385; 60-72 y, n = 172) and one group of healthy elderly subjects (60-89 y, n = 16). Expiratory flows and induced sputum cell counts were analyzed. Airway obstruction was more marked in elderly asthmatics compared with healthy elderly or younger asthmatic subjects (p < 0.01). An increase in sputum neutrophils and a decrease in macrophages and lymphocytes were observed in elderly asthmatics (p < 0.0001). Neutrophil percentages significantly increased with asthma severity in the young and the middle-aged groups, while they remained similar in elderly asthmatics regardless of asthma severity (p < 0.05). Neutrophil percentages weakly correlated with the dose of ICS in all asthmatics (r = 0.17, p < 0.0001). Age and dose of ICS were independent predictors of neutrophil percentage in asthmatic subjects in a regression model (R(2) = 0.12). Asthma in the elderly is associated with a more marked airway obstruction and sputum neutrophilia. Both age and the dose of corticosteroids need to be considered in the interpretation of the clinical relevance of sputum neutrophil count.

Airway refractoriness to inhaled mannitol after repeated challenge

Exercise and inhaled mannitol are thought to cause bronchoconstriction through a similar mechanism in asthma. The response to exercise becomes refractory with repeated challenges. This study aimed to investigate whether repeated challenge with mannitol induces refractoriness, as with exercise. Forty-one children with asthma underwent two consecutive dose-response mannitol challenges (Phase 1); the second challenge proceeded after recovery (FEV(1) : 95% or more of baseline value) from the first. The response to mannitol was expressed as a provocative dose causing a 15% fall in FEV(1) (PD(15) ) and the response-dose ratio (RDR) (% fall in FEV(1) /cumulative dose). In 18 subjects who were deemed to have mannitol refractoriness in Phase 1, a mannitol challenge was performed before and after a methacholine challenge (Phase 2). In Phase 1, the time taken for the FEV(1) to recover after the first mannitol challenge ranged from 20 to 100 min with a median of 50 min. In the 23 subjects with a measurable mannitol PD(15) in both challenges, the geometric mean (95%CI) PD(15) in the second challenge (163 mg [114-232]) was significantly higher than that in the first challenge (66 mg [50-88], P < 0.001). The geometric mean (95%CI) RDR decreased from the value of 0.083%/mg (0.055-0.125) in the first challenge to 0.029%/mg (0.017-0.048) in the second challenge (P < 0.001). In Phase 2, prior challenge with methacholine or mannitol did not significantly alter subsequent bronchoconstriction to the opposite challenge. Repeated challenge with mannitol resulted in less bronchoconstriction when compared with the initial challenge. This refractoriness seems not to be attributable to functional loss of responsiveness or non-specific effect of prior bronchoconstriction.

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.

Cysteinyl leukotriene antagonism inhibits bronchoconstriction in response to hypertonic saline inhalation in asthma

In asthma, cysteinyl leukotrienes (CysLTs) play varying roles in the bronchomotor response to multiple provocative stimuli. The contribution of CysLTs on the airway's response to hypertonic saline (HS) inhalation in asthma is unknown. Whether polymorphisms in the leukotriene biosynthetic pathway affect the contribution of CysLTs to this response is also unknown. In a prospective, randomized, double-blind, placebo-controlled cross-over study, mild and moderate asymptomatic asthmatics underwent inhaled 3% HS challenge by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min) 2 h after one dose of montelukast (a CysLT receptor 1 [CysLTR1] antagonist) or placebo, and after three-week courses. We examined the effect of the leukotriene C(4) synthase (LTC(4)S) polymorphism (A-444C) on the efficacy of montelukast against HS inhalation in an exploratory manner. In 37 subjects, 2 h after administration of montelukast, the mean provocative dose of HS required to cause a 20% drop in FEV(1) (HS-PD(20)) increased by 59% (9.17 ml after placebo vs. 14.55 ml after montelukast, p=0.0154). Three weeks of cysLTR1 antagonism increased the HS-PD(20) by 84% (10.97 vs. 20.21 ml, p=0.0002). Three weeks of CysLTR1 antagonism appeared to produce greater effects on blocking bronchial hyper-responsiveness (2 h vs. three-week HS-PD(20) values 14.55 vs. 20.21 ml respectively, p=0.0898). We did not observe an effect of the LTC(4)S polymorphism on the response to CysLTR1 antagonism in this cohort. A significant proportion of HS-induced bronchoconstriction is mediated by release of leukotrienes as evidenced by substantial acute inhibition with a CysLTR1 antagonist. There was a trend toward greater inhibition of bronchial responsiveness with three weeks of therapy as opposed to acute CysLTR1 antagonism. Clinicaltrials.gov registration number NCT00116324.

Comparison of central and peripheral airway involvement before and during methacholine, mannitol and eucapnic hyperventilation challenges in mild asthmatics

Testing for airway hyperresponsiveness with indirect stimuli as exercise or mannitol has been proposed to better reflect underlying airway inflammation, as compared with methacholine (MCh), believed to act directly on airway smooth muscle cells. To investigate whether different direct and indirect stimuli induces different patterns of obstruction, recorded as central and peripheral resistance, and to see whether baseline resistance could predict a positive response to direct or indirect provocation. Thirty-four mild asthmatics and 15 controls underwent MCh, mannitol and eucapnic voluntary hyperventilation (EVH) challenge tests. The response was evaluated with spirometry and impulse oscillometry (IOS). Twenty-three out of 34 asthmatics were positive to either EVH (22) or mannitol (13). Those positive to mannitol had a significant increased baseline value of IOS parameters such as ΔR5-R20 and AX. Twelve of the asthmatics had a 10% fall or more in forced expiratory volume in 1 s (FEV(1)) in all three challenge tests. However, the response pattern measured by IOS did not differ between the tests. When the limit for a positive mannitol provocation was set to 10% fall in FEV(1), 16 out of 19 mannitol-positive patients were also positive to EVH. Even in mild asthmatics, a substantial number had a positive indirect test. Mannitol FEV(1) provocative dose to decrease FEV(1) by 10% from baseline (PD10) was closely associated to EVH10%. No difference in bronchoconstrictive pattern could be seen between the different provocation tests, but those positive to mannitol had more peripheral airway involvement at baseline. This supports the idea that peripheral airway involvement is an important predictor of asthma airway reactivity.

Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial

In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n=16), SCIT (n=16) or pharmacotherapy alone (n=16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

A 10-year open follow-up of eczema and respiratory symptoms in patients with atopic dermatitis treated with topical tacrolimus for the first 4 years

Objectives: To examine the 10-year outcome of affected body surface area (BSA), respiratory symptoms, and serum IgE in adult AD patients 6 years after a 4-year intervention with topical tacrolimus.Methods: Patients who 10 years ago participated in a 4-year, open tacrolimus study (n = 65) were contacted for assessment of affected BSA, bronchial hyper-reactivity (BHR), respiratory symptoms, skin prick tests and serum IgE.Results: Altogether, 50 (77%) patients attended the follow-up visit. The median affected BSA decreased from 19% to 1.6% during the 10-year follow-up (p < 0.0001). Patients with active asthma and rhinitis symptoms at baseline reported a significant decrease at the follow-up (p = 0.02 andp = 0.01). In patients with BHR at baseline, the provocative dose of inhaled histamine producing a 15% decrease in FEV1 increased. Responders (≥ 60% improvement of affected BSA) to tacrolimus treatment at the 1-year visit had a significantly smaller affected BSA at the 4- and 10-year visits than non-responders (< 60% improvement). Responders also showed a significant decrease in serum IgE at the follow-up visit compared to baseline (p = 0.002).Conclusions: The long-term, effective treatment of patients with AD may have a beneficial effect on affected BSA, respiratory symptoms, and serum IgE.

Airway responsiveness measured by body plethysmograph connecting a circuit of an inhalation system of serially concentrated bronchoconstrictant

We developed a new methodology to examine the bronchial response to the bronchoconstrictants, acetylcholine and methacholine. An inhalation device was connected to the body plethysmograph circuit so that a minute inhalation of serially concentrated bronchoconstrictant could be quickly switched to the circuit of the measurement of the airway resistance. The following were calculated: airway responsiveness in terms of sensitivity, provocative dose to increase the airway resistance up to 35% from the baseline. PC35 or PD35 and the reactivity, the slope of the declining specific airway conductance and %delta SGaw. The airway responsiveness was examined in asthmatics, COPD outgrew -childhood asthma patients and normal subjects. These three groups were categorised differently from each other in both sensitivity and reactivity.

Role of 5‐HT2A, 5‐HT4 and 5‐HT7 receptors in the antigen‐induced airway hyperresponsiveness in guinea‐pigs

A possible role of 5-hydroxytryptamine (5-HT) in the origin of antigen-induced airway hyperresponsiveness (AI-AHR) has been scarcely investigated. To explore the participation of different 5-HT receptors in the development of AI-AHR in guinea-pigs. Lung resistance was measured in anaesthetized guinea-pigs sensitized to ovalbumin (OVA). Dose-response curves to intravenous (i.v.) acetylcholine (ACh) were performed before and 1 h after antigenic challenge and expressed as the 200% provocative dose (PD(200)). Organ bath experiments, confocal microscopy and RT-PCR were additionally used. The 5-HT content in lung homogenates was measured by HPLC. Antigenic challenge significantly decreased PD(200), indicating the development of AI-AHR. This hyperresponsiveness was abolished by a combination of methiothepin (5-HT(1)/5-HT(2)/5-HT(5)/5-HT(6)/5-HT(7) receptors antagonist) and tropisetron (5-HT(3)/5-HT(4) antagonist). Other 5-HT receptor antagonists showed three different patterns of response. Firstly, WAY100135 (5-HT(1A) antagonist) and ondansetron (5-HT(3) antagonist) did not modify the AI-AHR. Secondly, SB269970 (5-HT(7) antagonist), GR113808 (5-HT(4) antagonist), tropisetron or methiothepin abolished the AI-AHR. Thirdly, ketanserin (5-HT(2A) antagonist) produced airway hyporresponsiveness. Animals with bilateral vagotomy did not develop AI-AHR. Experiments in tracheal rings showed that pre-incubation with LP44 or cisapride (agonists of 5-HT(7) and 5-HT(4) receptors, respectively) induced a significant increase of the cholinergic contractile response to the electrical field stimulation. In sensitized lung parenchyma strips, ketanserin diminished the contractile responses to ACh. Sensitization was associated with a ninefold increase in the 5-HT content of lung homogenates. Confocal microscopy showed that sensitization enhanced the immunolabelling and co-localization of nicotinic receptor and 5-HT in airway epithelium, probably located in pulmonary neuroendocrine cells (PNECs). RT-PCR demonstrated that neither sensitization nor antigen challenge modified the 5-HT(2A) receptor mRNA levels. Our results suggested that 5-HT was involved in the development of AI-AHR to ACh in guinea-pigs. Specifically, 5-HT(2A), 5-HT(4) and 5-HT(7) receptors seem to be particularly involved in this phenomenon. Participation of 5-HT might probably be favoured by the enhancement of the PNECs 5-HT content observed after sensitization.

Experimental hookworm infection: a randomized placebo‐controlled trial in asthma

BackgroundEpidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.ObjectivesTo determine the effects of experimental hookworm infection in asthma.MethodsThirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD20AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects.ResultsMean PD20AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: −1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated.ConclusionsExperimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.Cite this as: J. R. Feary, A. J. Venn, K. Mortimer, A. P Brown, D. Hooi, F. H. Falcone, D. I. Pritchard and J. R. Britton, Clinical & Experimental Allergy, 2010 (40) 299– 306.

The impact of inhaled corticosteroids on cough and bronchial hyperreactivity in cough variant asthma

Classic asthma is characterized by cough, wheezing and dyspnea. Cough, however, may be the sole presenting symptom of asthma and this type of asthma is known as cough-variant asthma. The therapeutic approach to cough variant asthma is similar to that of the typical form of asthma. A diagnosis of cough-variant asthma is made when a chronic cough is associated with airway hyperresponsiveness and a favorable response to asthma therapy in the absence of other discernible cause. The aims of this study were to analyse the influence of inhaled corticosteroids on cough and bronchial hyperresponsiveness. The study included 55 patients with cough as the sole presenting symptom. 40 patients (Group A) were treated with inhaled corticosteroids and beta2 agonists for eight weeks while 15 patients (Group B) were treated only with oral beta2 agonists. The nonspecific bronchoprovocative test with histamine was performed on all the patients before the treatment and after the examination and there was established the provocative dose of histamine causing the 20% fall in FEVI (PD20). At the end of the study in Group A we found a statistically significant decrease of PD20 0.98 +/- 0.86 vs. 1.58 +/- 1.06 (p < 0.005), while in Group B there were no significant changes. In 90% of the patients treated with inhaled corticosteroids the cough was completely relieved while in 80% of the patients treated with only beta2 agonists the cough has remained unchanged. Inhaled corticosteroids are choice drugs for the treatment of cough-variant asthma because they relieve cough and decrease bronchial hyperresponsiveness, thus ultimately reducing the risk of classic asthma.

Methacholine challenge – Comparison of an ATS protocol to a new rapid single concentration technique

Bronchial methacholine challenge is well established in asthma diagnostics and research. ATS guidelines propose a five step standard dosimeter (SDM) protocol with incremental concentrations of methacholine to calculate the concentration causing a 20% drop in FEV(1) in an individual (PC(20)FEV(1)). In contrast, the aerosol provocation system (APS) by Viasys automatically determines the administered dose of methacholine by measuring the effective nebulisation time and referring it to drug concentration and nebuliser power. Therefore, it offers a feasible and less time-consuming provocation procedure by applying incremental doses (PD(20)) of methacholine using a single concentration (16mg/mL methacholine, APS-SC). In this study we compared these two methods in 52 young adults (25+/-5.8 years). Following a screening visit, subjects were randomly assigned to undergo either SDM or APS-SC followed by the other method within 1 week. A close correlation between concentration and dosage causing a 20% fall of FEV(1) was found (r=0.69, p<0.001). Using the ATS categorisation of bronchial responsiveness we interpreted the results of the APS-SC method as follows: PD(20) methacholine<0.3mg as "moderate to severe BHR", 0.3 - 0.6mg as "mild BHR", 0.6 - 1.0mg as "borderline BHR", and>1.0mg as "normal bronchial response". We conclude that the five-step APS-SC is a suitable method, providing reliable results. In clinical practice the APS-SC is a timesaving procedure and less prone to errors since only one dilution of methacholine is necessary compared to the SDM.

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo‐controlled feasibility study

BackgroundEpidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.ObjectiveTo determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms.MethodsThirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD10AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks.ResultsMean maximum change in PD10AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (−1.67 and −1.16 doubling doses; mean difference −0.51, 95% confidence interval −1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups.ConclusionHookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.

Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica

Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024-0.97; P = 0.05]). Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.

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.

Are asymptomatic airway hyperresponsiveness and allergy risk factors for asthma? A longitudinal study

To the Editors: We read with interest the recent paper by van den Nieuwenhof et al. 1 who reported no statistically significant association of airway hyperresponsiveness (AHR) with asthma incidence over 14 yrs in 123 asymptomatic adolescents aged 10–22 yrs at baseline. They concluded that AHR is not a risk factor for the development of asthma in adulthood and that screening for AHR in adolescents to detect subjects at risk for asthma cannot be recommended. We similarly assessed the association between AHR at baseline and asthma incidence over 11.4 yrs among 172 asymptomatic children (44.2% with AHR (provocative dose causing a 20% fall in forced expiratory volume in one second <4 mg methacholine) at baseline) and 517 adults (31.7% with AHR at baseline) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) 2, 3. Asymptomatic adults were defined as those with a null symptomatic score according to Pekkanen et al. 4 over the previous 12 months. The score is based on asthma-like symptoms (wheeze with breathlessness, woken with chest tightness, attack of shortness of breath (SOB) at rest, attack of SOB after …

Airway hyperresponsiveness and airway inflammation in elite swimmers

The prevalence of respiratory symptoms and airway hyperresponsiveness (AHR) is high in elite athletes; swimmers have one of the highest prevalences. No consensus exists on what airway challenge to use when identifying AHR in elite athletes. Further, knowledge is sparse about when during their active sport career AHR develops and if there is an acute effect on the airway inflammation of a swimming training session. We aimed to (i) evaluate the airway response to a methacholine challenge, a eucapnic voluntary hyperpnoea (EVH) test, a field-based exercise test (FBT) and a laboratory-based exercise test (LBT) in adult elite swimmers; (ii) investigate airway responsiveness and airway inflammation in adolescent elite swimmers; and (iii) evaluate the acute effect of a training session in an indoor swimming pool on airway inflammation in adolescent elite swimmers. Two groups were studied. (i) In adult elite swimmers (n = 16), we examined airway response in four airway provocation tests: methacholine challenge, EVH test, FBT and LBT. (ii) In adolescent elite swimmers (n = 33), we examined airway responsiveness to EVH and methacholine, and airway inflammation and compared the findings with those in asthmatic adolescents (n = 32) and unselected adolescents (n = 35). Further, we examined the acute effect of swimming on airway inflammation in a subpopulation of the adolescent swimmers (n = 21). Airway inflammation was evaluated using sputum induction, measurements of exhaled nitric oxide (FeNO) and exhaled breath condensate (EBC). Of 16 adult swimmers, eight (50%) had AHR; five of the eight (63%) were identified with the EVH test, four (50%) with the FBT, four (50%) with the LBT and none with the methacholine challenge [provocative dose of methacholine causing a 20% fall in FEV1 (PD(20)) <or= 2 micromol]. There were no differences in the prevalence of AHR to either EVH or methacholine (PD(20) <or= 8 micromol) among the adolescent swimmers, the asthmatic adolescents and the unselected adolescents. When looking at airway responsiveness as a continuous variable, the swimmers were more responsive to EVH than were the unselected subjects, and less responsive to methacholine than were the asthmatic adolescents. There were no differences in FeNO, EBC pH or in the cellular composition of the sputum among the three groups. Lung function, FeNO, EBC pH, EBC lactate and differential cell counts in sputum were not acutely affected by the swimming session. We found that the EVH test is the most sensitive test for identifying AHR in elite athletes when using the diagnostic criteria set forward by the International Olympic Committe. Whereas a high prevalence of AHR in adult swimmers was found, the prevalence of AHR in the adolescent swimmers did not differ from that in unselected adolescents nor did the adolescent swimmers have signs of airway inflammation. There was no acute effect of a swimming training session in an indoor chlorinated pool on lung function or airway composition in adolescent swimmers. We believe that elite swimming results in airway changes with AHR and airway inflammation.

Survey of airborne pollen in Hubei province of China

To study the genera and seasonal distribution of airborne pollen in Hubei province of China, and its relationship with pollinosis. From November 2003 to October 2004, an airborne pollen investigation was performed in 16 chosen areas in 12 cities of Hubei province using gravity sedimentation technique. Meanwhile, univalent skin prick tests of pollens were performed and the invasion season was studied on 2,300 patients with pollinosis. Among them, 352 cases underwent the airway responsiveness measurements, and the correlation between airway responsiveness and results of pollen count was analyzed. A total of 61 pollen genera were observed and 257,520 pollens were collected. The peak of airborne pollen distribution occurred in two seasons each year: spring (March and April) and autumn (from August to October). The attack of pollinosis corresponded to the peak of pollen distribution. There was a significantly negative relationship between the provocation dose causing a 20% decrease of forced expiratory volume in one second (FEV1) from baseline and airborne pollen concentration (r= -0.6829, P < 0.05). This study provides useful information for airborne pollen epidemiology of Hubei province, and it provides important insights to clinical prevention, diagnosis, and treatment of pollen-related allergic diseases.

Maize food allergy: a double‐blind placebo‐controlled study

Maize allergy is not very common especially in Europe. The number of studies that address IgE mediated maize allergy is all too few. Evaluate subjects with a history of maize allergy by double-blind, placebo-controlled food challenge; identify the spectrum of symptoms manifested during challenge; determine the lowest provocation dose (PD) during challenge; determine the performance characteristics of maize skin prick test and specific IgE. Twenty-seven patients with a history of maize allergy were enrolled to be evaluated by skin test, specific IgE and double-blind placebo-controlled maize challenge. Forty-eight percent of the patients were challenge positive. PD range was 0.1-25 g. Fifty-four percent of the maize allergic subjects had a PD that was < or = 2.5 g; two subjects reacted to 100 mg of maize. Comparison of maize specific IgE levels and skin test results to the challenge results revealed the following (specific IgE level/skin testing): sensitivity 1.00/0.846, specificity 0.077/0.384, positive predictive value 0.520/0.579, and negative predictive value 1.00/0.714. Maize is a cause of IgE-mediated allergic reactions to foods in adults and children. Nearly half of the subjects recruited were confirmed by challenge to be allergic to maize. Twenty-three percent of the positive challenge patients manifested symptoms that involved two organ systems, thus fulfilling the criteria for maize induced anaphylaxis. Maize is allergenic and can pose a risk for symptomatic food allergy at a dose of 100 mg.

Maize allergy: what we have learned so far

Maize allergy: what we have learned so far