Changes In Bronchial Hyperresponsiveness Research Articles

Sex-based differences in factors associated with bronchial hyperresponsiveness in adolescents with childhood asthma

BackgroundBronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma.PurposeWe aimed to investigate the factors associated with BHR in adolescents with childhood asthma.MethodsTwo hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV1] [PC20], n=113) or non-BHR group (≥25 mg/mL of PC20, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC20 at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents.ResultsMold sensitization (adjusted odds ratio [aOR], 5.569; P=0.005) and increased blood eosinophil count (aOR, 1.002; P=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; P=0.010) but not girls. A reduced FEV1/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; P=0.007). BHR decreased with age throughout childhood. A low methacholine PC20 at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; P=0.028).Conclusion Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.

Does new sensitization correlate with nasal symptoms in children with allergic rhinitis?

To evaluate the correlation between the increased number of sensitized allergens and nasal symptoms in patients with allergic rhinitis who were sensitized to house dust mites (HDMs). Among the patients who were enrolled in the Allergic Rhinitis Cohort Study for Kids, 174 children with rhinitis symptoms who were sensitized to HDMs were included in the analysis. Skin prick tests, serum total immunoglobulin E, eosinophil count, and bronchial provocation tests were carried out during the initial and 3-year follow-up visits. The patients were divided into two groups depending on the change in the number of sensitized allergens: increased number of sensitized allergens (group I) and maintained or reduced number of sensitized allergens (group II). In the analysis of allergen sensitization from baseline to the 3-year follow-up, no significant correlation was observed between the changes in the number of allergens and the total nasal visual analog scale score (R2 < 0.001, P = .813). Furthermore, the comparison of demographic data and immunological factors between groups I and II did not show any significant differences. The changes in bronchial hyper-responsiveness were not significantly different between the two groups (P = 1.000). New sensitization may not be correlated with nasal symptoms in patients in Asian countries where HDMs play a major role as a dominant allergen. Although further investigation must be conducted, the importance of new sensitization as an indicator of treatment outcome should be reconsidered in individuals in Asia. 2b Laryngoscope, 130: 1864-1871, 2020.

Association of symptom control with changes in lung function, bronchial hyperresponsiveness, and exhaled nitric oxide after inhaled corticosteroid treatment in children with asthma

BackgroundA key therapeutic approach to asthma, which is characterized by chronic airway inflammation, is inhaled corticosteroid (ICS). This study evaluated the association of symptom control with changes in lung function, bronchial hyperresponsiveness (BHR), and exhaled nitric oxide (eNO) after ICS treatment in asthmatic children. MethodsA total of 33 children aged between 5 and 12 years with mild to moderate persistent asthma were treated with 160 μg ciclesonide per day for 3 months. At days 0 and 90, the following parameters were assessed: asthma symptom scores; lung function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25–75% of forced vital capacity (FEF25–75%); BHR to methacholine and adenosine 5-monophosphate (AMP); and eNO. ResultsAsthma symptom scores, lung function parameters, BHR to methacholine and AMP, and eNO levels at day 90 were significantly improved versus day 0 (all p < 0.001). Symptom scores at day 90 were not correlated with changes in lung function and BHR to methacholine during the follow-up period, whereas those at day 90 were more closely correlated with changes in BHR to AMP (r = 0.511, p = 0.003) than with eNO (r = −0.373, p = 0.035). Additionally, changes in PC20 AMP were correlated with changes in PC20 methacholine (r = 0.451, p = 0.011) and eNO (r = −0.474, p = 0.006). ConclusionsChanges in the BHR to AMP, and to a lesser extent eNO, correlate with asthma symptom control after ICS treatment. BHR to AMP may better reflect the relationship between improved airway inflammation due to ICS treatment and asthma symptoms.

Experimental Asthma Induced By Tropomyosins from Cockroach and Shrimp: Insights into in Vivo Cross-Reactivity

In vivo cross-reactivity among tropomyosins, major pan-allergens among invertebrates, is not established. Our aim was to investigate the effects of purified tropomyosins from cockroach (recombinant Pera7) and shrimp (natural Litv1) on airway inflammation and hyperresponsiveness in a mouse model of asthma. Balb/c mice, 4 to 6 weeks-old, were sensitized twice with 50μg of rPera7 or nLitv1 intraperitoneally with 1 mg alum, and challenged with 50μg of rPer7 or nLitv1 intranasally for three days. A group was sensitized with rPera7 and challenged with nLitv1 under same conditions. Controls received saline on same days. Twenty-four hours after the last challenge, mice were ventilated with FlexiVent®, and in vivo bronchial hyperresponsiveness was evaluated with inhaled methacholine (6.25,12.5,25 and 50mg/ml). After ventilation, bronchoalveolar lavage fluid (BALF) was collected and cell counts were performed. Sensitization and challenge of mice with rPera7 or nLitv1 resulted in increase in bronchial hyperresponsiveness, given by increase in resistance and elastance. Total cells in BALF increased in rPera7 and nLitv1 groups, as compared to controls. There was increase in macrophages (5x104 vs 1x105 and 3x105 for rPera7 and nLitv1, p<0.001) and eosinophils (2x103 vs 1.4x105 and 9.1x105, p<0.001). Mice immunized with rPera7 and challenged with nLitv1 showed no changes in bronchial hyperresponsiveness or cells on BALF as compared to controls. Experimental asthma induced by tropomyosins from cockroach and shrimp mimicked the main characteristics of human asthma. Despite the high degree of sequence identity and IgE immunologic cross-reactivity, our data suggested that in vivo cross-reactivity of these tropomyosins is unlikely.

A half doubling dose change in bronchial hyperresponsiveness in a population represents an important difference.

BackgroundThe prevalence of asthma has increased over recent decades and the reasons for this are poorly understood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness (BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference in BHR for an individual is accepted to be around one doubling dose, the minimum important change in a population is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and cholesterol, a change that is not clinically important in an individual may be extremely important in public health terms.FindingsTo assess the potential impact of a small absolute change in BHR across a population, we modelled the effect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population. We calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR by 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe asthma, this would be highly significant in public health terms.ConclusionsWe propose that a one half doubling dose worsening in BHR across a population may represent an important change.Electronic supplementary materialThe online version of this article (doi:10.1186/2213-0802-1-4) contains supplementary material, which is available to authorized users.

Acute respiratory effects in firefighters

Associations between acute respiratory inflammatory responses, changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and exposure to fire smoke were studied. The study comprised 51 firefighters. Blood samples were taken within 24 hr following exposure to fire smoke, and after a week and 3 months. Sputum was induced within 5 days post-exposure and subjects underwent spirometry and methacholine provocation one week post-exposure. Exposure was registered by a questionnaire. No changes were observed following smoke exposure in bronchial hyperresponsiveness and serum pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters (44%) elevated sputum neutrophil levels (≥60%) were found. Serum IL-8 concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated neutrophil levels in sputum were associated with elevated serum IL-8 (β = 0.010, P = 0.004) and TNFα (β = 0.005, P = 0.034) levels within 24 hr post-exposure and IL-8 elevation lasted up to 3 months. Acute exposure to fire smoke induces acute neutrophilic airway and long-lasting systemic inflammation in healthy firefighters in the absence of bronchial hyperresponsiveness.

Changes in Exhaled Nitric Oxide Measured by Two Offline Methods Predict Improvements in Bronchial Hyperresponsiveness after Inhaled Steroid Therapy in Japanese Adults with Asthma

The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. No studies have examined the relationship between the change in FeNO levels measured offline and changes in bronchial hyperresponsiveness (BHR) in asthmatic patients treated with inhaled corticosteroids (ICS). The objective of this study was to investigate the relationship between the change in FeNO levels measured offline and the change in BHR to acetylcholine in asthmatic patients taking ICS. The study population comprised 41 ICS-treated asthmatics from our outpatient clinic. We measured FeNO levels by two methods -with a Sievers kit ("FeNOs") and with a kit from the Center for Environmental Information Science, Japan ("FeNOc") at baseline and after 1 year of regular treatment. We also used spirometry to test BHR to acetylcholine (PC(20Ach)). The mean of duration of observation was 406 days. There were significant relationships between DeltalogPC(20Ach) and logPC(20Ach) (r = -0.877, P < 0.001), FeNOs (r = 0.465, P = 0.002), and FeNOc (r = 0.524, P = 0.004) at baseline, but not with age, the dose of ICS, FEV(1), or %FEV(1). Moreover, there was a significant relationship between DeltalogPC(20Ach) and DeltaFeNOs (r = -0.386, P = 0.013) and DeltaFeNOc (r = -0.473, P = 0.004), but not with DeltaFEV(1). Changes in FeNOs and FeNOc correlated with improvements in BHR to acetylcholine in adult asthmatics after ICS therapy. Our findings suggest that offline monitoring of FeNO will facilitate the management of bronchial asthma in patients treated with ICS.

Allergic Rhinitis and Onset of Bronchial Hyperresponsiveness

Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies. To estimate the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period. BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey. BHR was defined as a >or=20% decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>or=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV(1)). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93] and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]). BHR "remission" was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]). Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis.

Changes in bronchial hyperresponsiveness following high‐ and low‐sulphite wine challenges in wine‐sensitive asthmatic patients

Previous studies suggest that challenge of most wine-sensitive asthmatic patients may not result in a reduction in forced expiratory volume in 1 s (FEV(1)). The aim of this study was to assess whether changes in bronchial hyperresponsiveness (BHR) occur following wine challenge of asthmatic patients who report sensitivity to wine, and whether such changes could help clarify the role of sulphite additives in wine-induced asthmatic responses. Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. FEV(1) and histamine PC(20) were measured before and after consumption of 150 mL of wine. None of the eight subjects demonstrated a clinically significant >or=15%) reduction in FEV(1) following challenge with either high- or low-sulphite wine. In contrast, one patient demonstrated clinically significant increase in BHR following challenge with both high- and low-sulphite wines, and a smaller increase in BHR following placebo challenge. A second patient showed a significant increase, while another showed a significant decrease in BHR following challenge with low-sulphite wine. A fourth patient showed borderline increases in BHR following challenge with both high- and low-sulphite wines. Although changes in BHR, in the absence of reductions in FEV(1), were observed in some asthmatic patients following wine challenge, these changes were not consistent with a single aetiology. Consequently, this study did not support a major role for the sulphite additives in wine-induced asthmatic responses in the patients studied. The aetiology of wine-induced asthma is likely to be complex and appears to vary among individuals who are sensitive to these drinks.

Longitudinal Changes in Bronchial Hyperresponsiveness and Exposure to High Levels of Domestic Pet Allergens

RATIONALE: Allergen exposure is thought to play an important part in the development and persistence of the asthma syndrome. We investigated the prognostic significance of exposure to domestic pet allergens in a large cohort of well-characterised asthmatics.

Antimicrobial strategies: An option to treat allergy?

Respiratory infections by bacteria and viruses often trigger symptoms of asthma in both adults and children. This observation and subsequent mechanistic studies have demonstrated important interactions among allergens, microbes and the atopic host. The mechanisms responsible for microbe-induced asthma exacerbations are only incompletely understood. A focal point of current research is the inflammatory response of the host following an encounter with a pathogenic microbe, including variations in chemokine and cytokine production and resulting in changes in bronchial hyper-responsiveness and lung function. Direct bronchial infection, exposure of nerves with resulting neurogenic inflammation and a deviated host immune response are among the mechanisms underlying these functional disorders. Lately, suboptimal innate immune responses, expressed as defective interferon production, have gained attention as they might be amenable to intervention. This review describes the suggested mechanisms involved in the complex interactions between ‘asthmagenic’ microbes, the immune system and atopy, based on in-vitro and in-vivo experimental models and epidemiological evidence. In addition, it provides a synopsis of potential therapeutic strategies either directly against the microorganisms or in respect to the associated inflammation.

Effect of nasal continuous positive airway pressure in uncontrolled nocturnal asthmatic patients with obstructive sleep apnea syndrome

The mechanisms of nocturnal asthma are intimately related to circadian rhythms, which influence inflammatory cells and mediators, hormone levels and cholinergic tone. Nocturnal airway narrowing in asthma is sometimes associated with sleep disorders, such as obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the association of nocturnal asthma and OSAS, and investigate the influence of continuous positive airway pressure (CPAP) therapy to improve nighttime symptoms in asthmatic patients with OSAS. Forty-three asthmatic patients who had nocturnal symptoms in spite of the optimal medical treatment according to the Global Initiative for Asthma guidelines and associated with snoring were studied. Pulmonary function tests (PFTs), asthma nighttime symptom scores, and polysomnography were performed on all patients. We treated the patients with an apnea-hypopnea index (AHI) 15 (moderate-severe OSAS) (n=16) with CPAP during 2 months. After 2 months, PFT, asthma nighttime symptom scores were reperformed. There was no significant difference in PFT values before and after CPAP treatment in OSAS patients. Asthma nighttime symptom scores were improved significantly (P<0.05) after CPAP treatment. In conclusion, in some patients with nocturnal asthma, OSAS may be responsible disease for nocturnal symptoms. In this condition, CPAP improves nocturnal symptoms without amelioration in PFT abnormalities.

Dissimilarity between Seasonal Changes in Airway Responsiveness to Adenosine-5’-Monophosphate and Methacholine in Patients with Grass Pollen Allergic Rhinitis: Relation to Induced Sputum

Background: In patients with allergic rhinitis, bronchial hyperresponsiveness (BHR) and airway inflammation may increase during pollen exposure. BHR can be assessed by adenosine-5′-monophosphate (AMP) or methacholine challenge. It has been suggested that BHR to AMP is more closely related to airway inflammation than BHR to methacholine. Seasonal allergic rhinitis offers a dynamic model to study changes in BHR and airway inflammation during natural allergen exposure. Methods: We measured BHR [provocative concentration causing a 20% fall (PC₂₀) in forced expiratory volume in 1 s (FEV₁)] to AMP and methacholine, and induced sputum cells in 16 rhinitis patients before and during the 2001 grass pollen season. Results: There was a decrease in PC₂₀ methacholine during pollen exposure (geometric mean PC₂₀ from 3.22 to 1.73 mg/ml, p = 0.0023), whereas no reduction was observed for PC₂₀ AMP (p = 0.11). There was no increase in sputum eosinophils [pre: 0.69% (95% confidence interval 0.22–2.07); during: 1.85 (0.55– 5.6), p = 0.31]. Although the correlation of log PC₂₀ methacholine and log PC₂₀ AMP at baseline was good (r = 0.76, p = 0.001), individual seasonal changes (doubling concentrations) in PC₂₀ methacholine were not correlated with changes in PC₂₀ AMP (ρ = 0.21, p = 0.44). There was no correlation between baseline log PC₂₀ methacholine or seasonal changes in PC₂₀ methacholine and sputum eosinophils (p > 0.12, all correlations). In contrast, there was a significant correlation between seasonal changes in PC₂₀ AMP and changes in sputum eosinophils (ρ = –0.59, p = 0.025). Conclusions: These data show dissimilarity between seasonal changes in PC₂₀ AMP and methacholine in patients with seasonal allergic rhinitis. Moreover, PC₂₀ AMP seems to be more closely related to sputum eosinophils than PC₂₀ methacholine. The clinical significance of this discrepancy is unclear.

Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: A 5-year prospective follow-up study of 42 highly trained swimmers

Abstract Background: Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. Objective: The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. Methods: Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers). Results: Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P = .025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P = .023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P = .025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P = .0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P = .033 and P = .0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period ( P = .17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P = .019). Conclusion: In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career. (J Allergy Clin Immunol 2002;109:962-8.)

Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: a 5-year prospective follow-up study of 42 highly trained swimmers.

Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers). Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P =.025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P =.023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P =.025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P =.0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P =.033 and P =.0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period (P =.17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P =.019). In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career.

Comparison of oral montelukast and inhaled fluticasone in the treatment of asthma associated with chronic rhinopolyposis: a single-blind, randomized, pilot study

Background: Rhinopolyposis is considered to be a non-immunoglobulin E-mediated inflammatory condition of the nose and sinuses, often associated with chronic rhinitis and asthma. Inhaled corticosteroids are currently the most commonly used anti-inflammatory agents for the chronic treatment of asthma and rhinopolyposis. Recently, montelukast, a selective cysteinyl leukotriene receptor antagonist indicated for the prophylaxis and treatment of asthma, has been shown to be effective in controlling rhinopolyposis and related symptoms. Objective: The aim of this study was to compare the short-term clinical efficacy of montelukast with that of fluticasone propionate in patients with asthma associated with rhinopolyposis. Methods: In this prospective, single-blind, randomized, pilot study, 12 out-patients with asthma associated with rhinopolyposis were given oral montelukast (10 mg once daily) or inhaled fluticasone propionate (intranasal suspension 50 μg and spray 250 μg twice daily). At baseline and after 30 days of treatment, the patients completed an asthma and rhinitis questionnaire and underwent nasal endoscopy, pulmonary function tests, and bronchial provocation testing. Results: Of the 12 study patients (9 men, 3 women), 7 were randomized to the montelukast group and 5 to the fluticasone group. There were no significant differences in baseline characteristics between the 2 treatment groups. After treatment, improvements in nasal and respiratory symptoms and nasal endoscopy results were found in 6 patients, 3 in each treatment group. No significant differences in the peak expiratory flow rate, forced expiratory volume in 1 second, or bronchial hyperresponsiveness changes after treatment were observed between the 2 groups. Conclusions: Our preliminary data show a comparable effect on respiratory and nasal symptoms and pulmonary function test results between oral montelukast and inhaled fluticasone in this small patient population, suggesting that leukotriene-receptor antagonists might be considered an alternative to inhaled corticosteroids in the treatment of asthma associated with rhinopolyposis.

Changes in FVC During Methacholine-Induced Bronchoconstriction in Elderly Patients With Asthma: Bronchial Hyperresponsiveness and Aging

We evaluated whether aging may produce changes in bronchial hyperresponsiveness, risk of enhanced bronchoconstriction, and changes of bronchoconstriction perception. Each subject underwent a methacholine bronchial challenge. Methacholine challenge was stopped when one of the following conditions occurred: (1) plateau of bronchoconstriction; (2) decrease of FEV(1) > 40%; (3) FEV(1) drop below 1 L; or (4) excessive respiratory discomfort. Methacholine dose-response curves were plotted both for FVC and FEV(1). The provocative dose of methacholine causing a 20% decrease in FEV(1) with respect to baseline (PD(20)) and the fall in FVC (DeltaFVC) at PD(20) were computed. The Borg scale was used for scoring the perception of respiratory discomfort. We compared 17 young asthmatic patients (aged 22 to 45 years) with 17 older asthmatic patients (aged 63 to 78 years) selected on the basis of similar baseline pulmonary function and disease duration. No significant between-group difference was found in PD(20) and in plateau development. Conversely, DeltaFVC was significantly higher in the older group (mean +/- SD, 15.5 +/- 3.9% vs 11.6 +/- 5.5% in younger patients). In addition, DeltaFVC showed a positive linear relationship with age (p = 0.0026). Elderly subjects were less aware of bronchoconstriction during the methacholine challenge (p = 0.04). In elderly patients with asthma having comparable pulmonary function and disease duration, bronchial responsiveness is not different from that observed in younger asthmatic patients. Nevertheless, in such patients, an age-related tendency to an enhanced bronchoconstriction and a reduced perception of the degree of bronchoconstriction exist.

Development of Bronchial Hyperresponsiveness During Childhood

Bronchial hyperresponsiveness (BHR) produces the characteristic pathological abnormalities seen in asthma and clearly plays a central role in the pathophysiology of asthma. The presence of BHR has been demonstrated in infants with asthma, as has the possibility of BHR persisting through the childhood period. The level of BHR may not only reflect the state of the airways, as a marker of airway dysfunction, but may also predict the persistent prognosis of the disease. Thus, measurement of BHR may provide important information about the symptoms and lung function in children with asthma. In view of multiple pathophysiological mechanisms, BHR does not seem to have a single cause. Many potential confounding variables, such as age, gender, and genetic status, and some environmental factors, such as allergens, infections, and pollutants, could be responsible for the establishment of childhood BHR. There may be differences between the mechanisms that induce transient BHR and the mechanisms that induce persistent BHR. Also, there may be differences between the causes that induce BHR in the infantile period and the causes that maintain persistent BHR during childhood asthma. There is also disagreement as to the most suitable method to measure BHR in children, especially in infants. The assessment of BHR in young children has not been uniformly successful, and measurements of BHR changes over the childhood period are associated with a number of problems. To resolve these problems, there may be two ways to study childhood BHR. One is to use age-matched specific techniques to clarify the precise BHR in each age group; the other is to use simple techniques that can be performed over the childhood period on a large number of subjects. In studies of infantile respiratory dysfunction the ultimate goal is to establish a simple, noninvasive method by which measurements of respiratory function may be obtained in infants. Further investigations and acceptable methods will be needed to clarify the mechanisms involved in the establishment of asthma throughout the childhood period.

Equivalent asthma control after dose reduction with HFA-134a beclomethasone solution aerosol

Aim: The replacement of chlorofluorocarbon (CFC) by hydrofluoroalkane has the potential to improve airway deposition of BDP. We investigated whether HFA-BDP extra-fine solution aerosol 400 μ g day−1is as effective as CFC-BDP 1000 μ g day−1in patients with stable, moderate asthma, having persistent bronchial hyper-responsiveness.Patients and Methods: One hundred and fifty patients with moderate asthma from 20 centres, on inhaled steroids for ≤3 months, entered a 4-week run-in period with 1000 μ g day−1CFC-BDP. Patients were then allocated to a 10-week study phase, receiving CFC-BDP 1000 μ g day−1or HFA-BDP 400 μ g day−1. Symptom score and PEF were measured daily and recorded as biweekly means. Spirometry, PC20FEV1, blood eosinophils and serum ECP were determined on days 15, 29, 43 and 71, and compared to the last visit of the run-in period. All group members were trained in a quality control centre.Results: Treating the population of the HFA-BDP group (n=72) and the CFC-BDP group (n=78) did not show significant differences in terms of symptoms, lung function, airway hyperresponsiveness and serum markers of inflammation at the end of the run-in period and the end of the study phase.Conclusion: Using HFA instead of a CFC metered dose inhaler, containing less than half the daily dose of BDP, allows control of symptoms and lung function parameters, without changes in bronchial hyperresponsiveness.

Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P = 0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: 1) In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. 2) MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms. 3) It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.