Hyperresponsiveness In Asthmatic Patients Research Articles

Mannitol Challenge to Assess Therapy Response in Asthmatic Children: An Interventional Cohort Study.

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4-16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50-458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122-635] vs. 635 mg [635-635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

The Effect of Zingiber cassumunar (Phlai Capsule) on Bronchial Hyperresponsiveness in Asthmatic Patients: A Randomized Controlled Trial

Background: Bronchial hyperresponsiveness (BHR) is a key feature of asthma. Compound D, an active compound in Phlai, can bind cysteinyl leukotrienes receptors that play a role for asthma treatment. Objective: To determine the effect of Phlai capsules on BHR measured by the methacholine challenge test. Materials and Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted in adult asthmatic patients with partly controlled symptoms. Each patient received four weeks of treatment with either Phlai or placebo separated by a 2-week washout period. The main outcome was provocative concentration of methacholine causing a 20% drop in FEV₁ (PC₂₀). Asthma control test (ACT) scores, and fractional exhaled nitric oxide (FeNO) levels were secondary end points. Results: Thirty patients were randomly allocated to either the Phlai or the placebo group. All patients had allergic rhinitis and received inhaled corticosteroid and long-acting beta2-agonist (ICS/LABA) or ICS alone. Four weeks after treatment, mean PC₂₀ in the Phlai group was higher than in the placebo group at 9.76±1.56 mg/mL versus 6.05±1.65 mg/mL (p=0.151). The improvement of ACT scores in the Phlai group was significantly higher than in the placebo group. FeNO levels decreased after treatment in the Phlai group. All patients tolerated the treatment well and had no side effects. Conclusion: In adult asthmatic patients with partly controlled symptoms, concomitant treatment with Phlai capsules tended to decrease BHR and significantly improve symptom scores. Keywords: Asthma; Asthma control test; Bronchial hyperresponsiveness; Zingiber cassumunar; Phlai

The effect of Zingiber cassumunar (Phlai capsule) on bronchial hyperresponsiveness in asthmatic patients

The effect of Zingiber cassumunar (Phlai capsule) on bronchial hyperresponsiveness in asthmatic patients

The role of endosomal toll-like receptors in asthma

Asthma is a heterogeneous inflammatory disease caused by association of genetic and environmental factors and its incidence has significantly increased over the latest years. The clinical manifestations of asthma are the result of airway hyper-reactivity to a variety of triggers such as aeroallergens, viral and bacterial components. Toll-like receptors (TLRs) are pathogen associated molecular pattern receptors, which are also expressed in the lung tissue as well as in several cells of the innate and adaptive immune system. Ligation of TLRs results in alterations in the expression of several inflammatory and anti-inflammatory mediators, which are known to be involved in the pathogenesis of asthma. The endosomal TLRs have been shown to be associated with the induction of asthmatic inflammation (TLR3), and with disease exacerbations (TLR7, TLR8 and TLR9). Targeting these receptors seems to be an effective choice for suppressing airway inflammation, eosinophilia and airway hyperresponsiveness in asthmatic patients. In this review we provide information regarding endosomal TLRs and their role in the pathogenesis of asthma as well as their potential use as targets for the development of novel treatments for the therapy of asthma.

P192 A pilot study to assess the influence of β2-adrenoceptor polymorphism on small airway function and asthma control

Introduction and ObjectivesIt is increasingly recognised that small airway dysfunction is associated with suboptimal asthma control. We have previously reported that β2-adrenoreceptor polymorphism at position 16 (i.e. Arg/Gly) is not...

Influence of β2-adrenergic receptor polymorphism on methacholine hyperresponsiveness in asthmatic patients

BackgroundWe previously reported that the β2-adrenergic receptor (ADRB2) polymorphism had no effect on bronchial hyperresponsiveness (BHR) to methacholine in asthmatic patients. We have now replicated this analysis in a different and larger cohort of patients. ObjectiveTo assess the effect of the ADRB2 polymorphism in methacholine-responsive patients with asthma. MethodsWe conducted a retrospective analysis of the effects of ADRB2 haplotypes at position 16 (Gly/Arg) and 27(Gln/Glu) in 449 patients with a physician diagnosis of asthma who were responsive to methacholine (ie, provocation concentration that caused a decrease in forced expiratory volume in 1 second [FEV1] of 20% [PC20], <8 mg/mL). ResultsNo differences were found in age, FEV1, or inhaled corticosteroid dose among the genotypes or haplotypes. No significant differences were found in methacholine PC20 (ie, <8 mg/mL) between the separate genotypes at position 16 or 27 or between the haplotypes at positions 16/27 combined. In addition, no significant differences were found among individual genotypes when stratified according to severity of BHR using different doubling dilution cutoff points for methacholine PC20 (ie, <4 mg/mL, <2 mg/mL, and <1 mg/mL). ConclusionWe have confirmed in this replication study that common ADRB2 genotypes or haplotypes at positions 16/27 do not influence BHR in methacholine-responsive patients with asthma.

Tryptase: Genetic and functional considerations

Tryptase is one of the main proteases located in the secretory granules of the mast cells, and is released through degranulation. It is therefore assumed to play an important role in inflammatory and allergic processes. Four genes are known to encode for these enzymes, with different alleles that give rise to different types of tryptases. The term “tryptase” generally refers to β-tryptase, which in vivo is a heterotetramer, possessing a structure of vital importance for enabling drug and substrate access to the active site of the molecule. Tryptase has been reported to possess antagonistic functions, since it plays an important role both in inflammatory phenomena and as a protector against infection. In allergic processes it is associated to bronchial hyperresponsiveness in asthmatic patients, where PAR-2 is of great importance as an airway receptor. Lastly, the genes that encode for tryptase are highly polymorphic and complex. As a result, it is important to establish a relationship between genotype and phenotype in disorders such as asthma, and to identify mutations that are presumably of pharmacological relevance.

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

Background/AimsMany patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin.MethodsThe clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus.ResultsForty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 ± 0.02) than in the oral responders (1.36 ± 0.03, p < 0.01) and in non-responders (n = 141, 1.37 ± 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR.ConclusionsA considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.

EDITORIAL

Respirology is continuing the process of renewing its Editorial Board as several Editorial Board members completed their terms of office in April this year. I am pleased to welcome Dr Patrick Gerard Moral who represents the Philippine College of Chest Physicians. More new members will be announced in the next issue of Respirology. For the fourth year, Respirology is proud to publish a series of reviews from the Presidents of the major international respiratory societies. We start a new series in this issue with Prof. Norbert Berend our APSR President and his review entitled ‘Mechanisms of Airway Hyperresponsiveness in Asthma’ with Dr Salome and Dr King as co-authors. This comprehensive review details the mechanisms of airway hyperresponsiveness in asthmatic patients and discusses the clinical implication of the most recent advances in this field and represents a major reference work on the topic of airway reactivity. The first highlight in this issue is the paper ‘Airway stenting for the treatment of laryngotracheal stenosis secondary to thyroid cancer’ by Dr Tsutsui and colleagues. This retrospective study investigates airway stenting in the palliation of thyroid cancer and discusses the best stents to manage this condition. This study is unique as very few centres in the world have such extensive experience in managing the challenging problem of tracheal obstruction secondary to thyroid cancer. The second highlight in this issue, ‘Recombinant human erythropoietin reduces epithelial cell apoptosis and attenuates bleomycin-induced pneumonitis in mice’ by Dr Yoshimi and colleagues, investigates the protective role of erythropoietin in mice and discusses its potential clinical use in prevention of lung injury in particular in acute diseases. The potential for this to be used in the clinic deserves further evaluation. Another study of anti-oxidant protection in lung injury is that of Dr Tajami and colleagues ‘Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced lung injury in mice’, in which they show that acute lung injury could be prevented by a free-radical scavenger in this rodent model. Clinical implications are also discussed. The paper ‘Trends in asthma prevalence and severity in Omani schoolchildren: Comparison between ISAAC phases I and III’ by Dr Al-Rawas and colleagues presents the results from two cross-sectional studies in Omani children conducted 6 years apart revealing an important underdiagnosis and under treatment of asthma in Omani children. Implications of these findings are discussed. In ‘Bosentan therapy in patients with pulmonary arterial hypertension: The relationship between improvements in 6 minute walk distance and quality of life’, Dr Strange and colleagues conclude from the results of a large study that Bosentan improved six-minute walk test and quality of life in pulmonary arterial hypertension patients and discuss the importance of considering improvement of quality of life in these patients in therapy. The paper ‘Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD’ by Dr Zang and colleagues investigates the effect of the polymorphism of the gene for the angiotensin-converting enzyme on skeletal muscle exercise performance in patients with COPD. Finally, the technical report ‘A competency-based test of bronchoscopic knowledge using the Essential Bronchoscopist: An initial concept study’ by Dr Davoudi and colleagues investigates the relevance and usefulness of the competency-based test of bronchoscopic knowledge the Essential Bronchoscopist as a complementary educational tool for bronchoscopists of different background and countries and conclude on the usefulness of this tool. I hope you enjoy this issue of Respirology.

Relationship between Exhaled Nitric Oxide Measured by Two Offline Methods and Bronchial Hyperresponsiveness in Japanese Adults with Asthma

Exhaled nitric oxide (eNO) is a useful marker of eosinophilic airway inflammation in asthmatics. There have been no studies to show the relationship between eNO measured by offline methods and the degree of bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids. The study population comprised asthmatics at our outpatient clinic. We measured eNO levels by two methods ("eNOs" was measured with a Sievers kit; and "eNOc" was measured with a kit from the Center for Environmental Information Science, Japan). We also used spirometry to test bronchial hyperresponsiveness to acetylcholine (PC(20Ach)). We recruited 192 stable asthmatics. There was a significant relationship between eNOs and eNOc (r = 0.919, p < 0.001). LogPC(20Ach) levels were negatively correlated with eNOs or eNOc levels (eNOs, r = -0.31, p < 0.001; eNOc, r = -0.23, p = 0.0013). We classified the subjects into two groups based on eNOs levels ((A) the subjects with high eNOs levels (n = 92) and (B) the subjects with normal eNOs levels (n = 100)) ; logPC(20Ach) was significantly correlated with eNOs (r = -0.34, p = 0.001) or eNOc (r = -0.28, p = 0.0075) but not correlated with %FEV(1) in (A), whereas logPC(20Ach) was not significantly correlated with eNO but significantly correlated with %FEV(1) (r = 0.33, p = 0.002) in (B). Levels of eNOs and eNOc were correlated with the degree of bronchial hyperresponsiveness to acetylcholine in adult asthmatics treated with inhaled corticosteroids. Our findings suggest that offline monitoring of eNO will facilitate the management of bronchial asthma in patients treated with these drugs.

Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-kappa B signaling pathways.

Airway infections induce hyper-responsiveness in asthmatic patients. Toll-like receptors (TLR) mediate inflammatory responses to microbes. Occurrence and effects of TLR2, TLR3 and TLR4 were examined in a mouse organ culture model of asthma focusing on the smooth muscle responses to bradykinin. TLR2, TLR3 and TLR4 mRNA, and TLR2 and TLR4 immunoreactivity were detected in the tracheal muscle layer. Tracheal organ culture for 1 or 4 days with lipopolysaccharide (LPS; TLR2/4 agonist) or polyinosinic polycytidylic acid (poly-I-C; TLR3 agonist) enhanced bradykinin- and [des-Arg(9)]-bradykinin-induced contractions. Simultaneous LPS and poly-I-C treatment resulted in synergistic enhancement of bradykinin-induced contraction. In carbachol-pre-contracted segments TLR stimulation induced less potent relaxations to bradykinin and [des-Arg(9)]-bradykinin. The LPS and poly-I-C enhancement of bradykinin-induced contraction was inhibited by the transcriptional inhibitor actinomycin-D, dexamethasone, the proteasome inhibitor MG-132 and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. LPS and poly-I-C induced translocation of NF-kappa B p65 to the nucleus and up-regulation of kinin B(1) and B(2) receptor mRNA. In summary, TLR2, TLR3 and TLR4 are expressed in the mouse tracheal smooth muscle. Costimulation of these receptors results in NF-kappa B- and JNK-mediated transcription of B(1) and B(2) receptor, inducing hyper-responsiveness to bradykinin.

Relationship Between Exhaled Carbon Monoxide and Airway Hyperresponsiveness in Asthmatic Patients

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose‐response curves were characterized by their sensitivity (PD20) and reactivity. Dose‐response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 ± 0.4 vs. 5.74 ± 0.57 ppm, p = 0.025) and in the negative response group (2.84 ± 0.25 vs 4.00 ± 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD20 was found (r = − 0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r2 = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.

Airway Hyperresponsiveness

Airway hyperresponsiveness is a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to the agonist. Measurements of airway responsiveness are useful in making a diagnosis of asthma, particularly in patients who have symptoms that are consistent with asthma and who have no evidence of airflow obstruction. These tests can be performed quickly, safely, and reproducibly. Certain inhaled stimuli, such as environmental allergens, increase airway inflammation and enhance airway hyperresponsiveness. These changes in airway hyperresponsiveness are of much smaller magnitude than those seen when asthmatic patients with persistent airway hyperresponsiveness are compared to healthy subjects. They are, however, similar to changes occurring in asthmatic patients that are associated with worsening asthma control. The mechanisms of the transient allergen-induced airway hyperresponsiveness are not likely to fully explain the underlying mechanisms of the persistent airway hyperresponsiveness in asthmatic patients.

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism.

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

New Considerations About Measuring Airway Hyperresponsiveness

Measuring airway responsiveness to inhaled bronchoconstrictor stimuli, such as methacholine or histamine, has become an important tool in the diagnosis of asthma. This is measured by patients inhaling increasing closes or concentrations of the bronchoconstrictor stimulus until a given level of bronchoconstriction is achieved. Inhaled allergens initiate processes that increase airway inflammation and enhance airway hyperresponsiveness in asthmatic subjects. Studies using inhaled allergen challenges have provided insight into how changes in airway hyperresponsiveness are regulated by induced inflammatory processes. These changes in airway hyperresponsiveness (1-2 doubling doses) have been shown to be of much smaller magnitude than those demonstrated when asthmatics with stable airway hyperresponsiveness are compared to normals (4-8 doubling doses). These allergen-induced changes would be of little relevance in subjects with normal airway responsiveness, because they would not increase the degree of airway responsiveness into the asthmatic range. They are, however, important in asthmatics who already have airway hyperrespon-siveness because they are similar to changes associated with worsening asthma control. It is likely that the mechanisms responsible for the changes in airway hyperresponsiveness following experimental allergen exposure are similar to those producing transient worsening of control in asthmatics. Nevertheless, it is unlikely that the mechanisms of the transient allergen-induced airway hyperresponsiveness will explain the underlying mechanisms of the persistent airway hyperresponsiveness in asthmatic patients when compared with normal individuals.

Reduced intracellular magnesium concentrations in asthmatic patients.

Magnesium is important in the regulation of bronchomotor tone, and low dietary intake of magnesium has been associated with airway hyperresponsiveness in epidemiological studies. The concentration of magnesium in serum, erythrocytes and urine in 49 patients with asthma (29 males, aged 15-65 yrs) and in 25 normal subjects (15 males, aged 17-36 yrs) was studied by atomic absorption. Magnesium concentrations were significantly lower in erythrocytes and urine in both atopic (n = 26) and nonatopic (n = 23) asthmatic patients as compared with the control group, whereas serum concentrations did not differ. The concentration of magnesium in erythrocytes was not related to the degree of airway obstruction as measured by forced expiratory volume in one second (FEV1) but was significantly correlated with airway hyperresponsiveness measured as the provocative concentration causing a 20% fall in FEV1 to inhaled acetylcholine (r = 0.64; p<0.05). In addition, a magnesium tolerance test showed increased retention of magnesium (58.9% of administered dose in asthmatic patients compared with 8.9% in normal subjects, p<0.05). In conclusion, the low cellular concentration of magnesium may be associated with airway hyperresponsiveness in asthmatic patients.

Allergy to mites: relation to lung function and airway hyperresponsiveness

Exposure to house-dust-mite allergens is an important cause of allergic reactions in sensitized patients. In community-based studies, sensitization to house-dust mites, as ascertained by a positive skin test or by an increased allergen-specific IgE level in serum, is associated with both diminished lung function and enhanced airway hyperresponsiveness. Sensitization to house-dust mites is an independent risk factor for the development of asthma, especially in areas which favor the growth of house-dust mites. In studies with asthmatic patients, however, the relationship between sensitization to mites and lung function or airway hyperresponsiveness is less clear. The selection of asthmatic individuals (with sensitization to other inhalant allergens) and the use of medication such as inhaled steroids may interfere with the demonstration of a possible association between mite allergy and lung function or airway hyperresponsiveness in asthmatic patients.

Effect of once daily and twice daily sustained release theophylline formulations on daytime variation of bronchial hyperresponsiveness in asthmatic patients.

BACKGROUND: Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the...

Seasonal differences in airway hyperresponsiveness in asthmatic patients: relationship with allergen exposure and sensitization to house dust mites.

The degree of airway hyperresponsiveness in allergic asthmatic patients may be influenced by changes in environmental exposure to inhalant allergens. This study investigates the relationship between seasonal changes in exposure to house dust mite (HDM) allergens and non-specific airway hyperresponsiveness in asthmatic patients with multiple sensitizations to inhaled allergens. In 43 asthmatic patients sensitized to several inhalant allergens, lung function (FEV1), airway hyperresponsiveness (PC20 histamine), serum total IgE, house dust mite (HDM) specific IgE and number of peripheral blood eosinophils were measured during autumn 1990 (September-November) and spring 1991 (March-May). During each season, floor dust samples were collected twice from living- and bedrooms and the concentration of the HDM allergens Der p 1 and Der p 2 determined. More severe airway hyperresponsiveness (lower PC20 histamine) during autumn was only found in patients sensitized to HDM (n = 32; autumn: 2.05 mg/mL, spring: 4.51 mg/mL (geometric means), P < 0.01), whereas in patients not sensitized to HDM (n = 11) similar values were observed in both seasons (3.44 and 4.52 mg/mL, respectively, P = 0.56). More severe airway hyperresponsiveness of HDM sensitized patients in autumn was significantly associated with higher Der p 1 concentrations in floor dust. Aside from airway hyperresponsiveness, seasonal changes in serum total IgE and number of peripheral blood eosinophils were seen in patients sensitized to HDM. In allergic asthmatic patients, airway hyperresponsiveness may increase during autumn, depending on sensitization to HDM and an increase of exposure to HDM allergen.