Changes In Airway Responsiveness Research Articles

Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment.

Bronchial thermoplasty is a recent treatment for asthma in which ablative thermal energy is delivered to specific large airways according to clinical guidelines. Therefore, current practice is effectively "blind," as it is not informed by patient-specific data. The present study seeks to establish whether a patient-specific approach based on structural or functional patient data can improve outcomes and/or reduce the number of procedures required for clinical efficacy. We employed a combination of extensive human lung specimens and novel computational methods to predict bronchial thermoplasty outcomes guided by structural or functional data compared with current clinical practice. Response to bronchial thermoplasty was determined from changes in airway responses to strong bronchoconstrictor simulations and flow heterogeneity after one or three simulated thermoplasty procedures. Structure-guided treatment showed significant improvement over current unguided clinical practice, with a single session of structure-guided treatment producing improvements comparable with three sessions of unguided treatment. In comparison, function-guided treatment did not produce a significant improvement over current practice. Structure-guided targeting of bronchial thermoplasty is a promising avenue for improving therapy and reinforces the need for advanced imaging technologies. The functional imaging-guided approach is predicted to be less effective presently, and we make recommendations on how this approach could be improved. NEW & NOTEWORTHY Bronchial thermoplasty is a recent treatment for asthma in which thermal energy is delivered via bronchoscope to specific airways in an effort to directly target airway smooth muscle. Current practice involves the treatment of a standard set of airways, unguided by patient-specific data. We consider the potential for guided treatments, either by functional or structural data from the lung, and show that treatment guided by structural data has the potential to improve clinical practice.

Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner.

Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.5 and then returned to normoxic conditions for the remainder of pregnancy. A control group was housed under normoxic conditions throughout pregnancy. Offspring were studied at 2 weeks (juveniles) and 8 weeks (adults), where lung volume was assessed by plethysmography, airway responsiveness to methacholine determined by the forced oscillation technique and lungs fixed for morphometry. IUGR offspring were lighter at birth, exhibited "catch-up growth" by 2 weeks, but were again lighter in adulthood. IUGR males were "hyper-responsive" at 2 weeks and "hypo-responsive" as adults, in contrast with IUGR females who were hyper-responsive in adulthood. IUGR males had increased inner and total wall thickness at 2 weeks which resolved by adulthood, while airways in IUGR females were structurally normal throughout life. There were no differences in lung volume between Control and IUGR offspring at any age. Our data demonstrate changes in airway responsiveness as a result of IUGR that could influence susceptibility to asthma development and contribute to sexual dimorphism in asthma prevalence which switches from a male dominated disease in early life to a female dominated disease in adulthood.

Paediatric total intravenous anaesthesia

### Key points Total i.v. anaesthesia (TIVA) has been used in adult practice since 1982 with target-controlled infusion (TCI) regimes available since 1989. Conversely, the use of TIVA in paediatric practice is far less routine with a survey finding only 10% of paediatric anaesthetists using it weekly or more.1 It has previously been the subject of a special edition of the journal Pediatric Anaesthesia 2 and the use for paediatric anaesthesia care is an increasing component at international meetings: educational sessions at the European Society for Paediatric Anaesthesia (2013), ASA (2014), and the Society for Intravenous Anaesthesia meeting in November 2015. Despite a number of obstacles (including interindividual pharmacokinetic and pharmacodynamic variability and safety concerns regarding propofol infusion syndrome—PrIS), there are notable benefits to TIVA and particular areas where it is indicated for anaesthetic or surgical reasons, where it may surpass volatile anaesthesia.3 It is a mandatory technique when inhalation agents are contraindicated. ### Advantages and disadvantages For physiological and clinical3 reasons (Table 2), TIVA has increasingly established a significant role in surgery in or around the airway (e.g. ENT) by obtunding airway reflexes (Table 2). The changes in airway reactivity facilitate extubation and result in a minimal incidence of laryngospasm and stridor …

A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity.

BackgroundObese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications. The purpose of this study was to determine the efficacy of pioglitazone, an anti-diabetic medication which can alter circulating adipokines and have direct effects on asthmatic inflammation, in the treatment of asthma in obesity.MethodsA two-center, 12-week, randomized, placebo-controlled, double-blinded trial. Treatments were randomly assigned with concealment of allocation. The primary outcome was difference in change in airway reactivity between participants assigned to pioglitazone versus placebo at 12 weeks.ResultsTwenty-three participants were randomized to treatment, 19 completed the study. Median airway reactivity, measured by PC20 to methacholine was 1.99 (IQR 3.08) and 1.60 (5.91) mg/ml in placebo and pioglitazone group at baseline, and 2.37 (15.22) and 5.08 (7.42) mg/ml after 12 weeks, p = 0.38. There was no difference in exhaled nitric oxide, asthma control or lung function between treatment groups over the 12 week trial. Participants assigned to pioglitazone gained a significant amount more weight than those assigned to placebo (pioglitazone group mean weight 113.6, CI 94.5-132.7 kg at randomization and 115.9, CI 96.9-135.1 at 12 weeks; placebo mean weight 127.5, CI 108.4 – 146.6 kg at randomization and 124.5, CI 105.4 – 143.6 kg at 12 weeks; p = 0.04).ConclusionsThis pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma.Trial RegistrationClinicaltrials.gov (NCT00634036)

Airway Hyperreactivity Is Delayed after Mild Neonatal Hyperoxic Exposure

Background: Wheezing disorders are prominent in former preterm infants beyond the neonatal period. Objectives: We used a neonatal mouse model to investigate the time course of airway hyperreactivity in response to mild (40% oxygen) or severe (70% oxygen) neonatal hyperoxia. Methods: After hyperoxic exposure during the first week of postnatal life, we measured changes in airway reactivity using the in vitro living lung slice preparation at the end of exposure [postnatal day 8 (P8)] and 2 weeks later (P21). This was accompanied by measures of smooth muscle actin, myosin light chain (MLC) and alveolar morphology. Results: Neither mild nor severe hyperoxia exposure affected airway reactivity to methacholine at P8 compared to normoxic controls. In contrast, airway reactivity was enhanced at P21 in mice exposed to mild (but not severe) hyperoxia, 2 weeks after exposure ended. This was associated with increased airway α-smooth muscle actin expression at P21 after 40% oxygen exposure without a significant increase in MLC. Alveolar morphology via radial alveolar counts was comparably diminished by both 40 and 70% oxygen at both P8 and P21. Conclusions: These data demonstrate that early mild hyperoxia exposure causes a delayed augmentation of airway reactivity, suggesting a long-term alteration in the trajectory of airway smooth muscle development and consistent with resultant symptomatology.

Airway responsiveness to mannitol 24 h after allergen challenge in atopic asthmatics.

Airway responsiveness to indirect stimuli correlates positively with airway inflammation. In atopic asthmatics, allergen inhalation is associated with an influx of inflammatory cells and increased responsiveness to the direct-acting stimuli methacholine at 3 and 24 h after exposure. We have shown mannitol responsiveness decreases 3 h after allergen inhalation. The current investigation assessed mannitol responsiveness 24 h after allergen challenge. Eleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24 h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured. Allergen challenge increased airway responsiveness to methacholine 24 h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9 mg/ml (1.8-19.4) to 2.2 mg/ml (0.81-5.89); P = 0.01. This coincided with a significant increase (P = 0.02) in FeNO levels. Conversely, allergen challenge decreased airway responsiveness to mannitol; geometric mean (95% CI) dose-response ratio was significantly higher after allergen exposure (57 mg/% FEV1 fall [27-121] to 147 mg/% FEV1 fall [57-379]; P = 0.03), and FeNO levels were not significantly increased (P = 0.054). Allergen-induced changes in airway responsiveness to direct and indirect stimuli are markedly different. The loss in responsiveness to mannitol is likely not explainable by a refractory state. The effect(s) of allergen exposure on airway responsiveness to indirect-acting stimuli require further investigation.

Nitrogen dioxide exposure and airway responsiveness in individuals with asthma

Controlled human exposure studies evaluating the effect of inhaled nitrogen dioxide (NO2) on the inherent responsiveness of the airways to challenge by broncho-constricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of the clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction (i.e. 70% of individuals with asthma exposed to NO2 at rest) experience increases in airway responsiveness following 30-min exposures to NO2 in the range of 200 to 300 ppb and following 60-min exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise.

Pharmacogenomics: novel loci identification via integrating gene differential analysis and eQTL analysis.

Nearly one-half of asthmatic patients do not respond to the most commonly prescribed controller therapy, inhaled corticosteroids (ICS). We conducted an expression quantitative trait loci (eQTL) analysis using >300 expression microarrays (from 117 lymphoblastoid cell lines) in corticosteroid (dexamethasone) treated and untreated cells derived from asthmatic subjects in the Childhood Asthma Management Program (CAMP) clinical trial. We then tested the associations of eQTL with longitudinal change in airway responsiveness to methacholine (LnPC20) on ICS. We identified 2484 cis-eQTL affecting 767 genes following dexamethasone treatment. A significant over-representation of lnPC20-associated cis-eQTL [190 single-nucleotide polymorphisms (SNPs)] among differentially expressed genes (odds ratio = 1.76, 95% confidence interval: 1.35-2.29) was noted in CAMP Caucasians. Forty-six of these 190 clinical associations were replicated in CAMP African Americans, including seven SNPs near six genes meeting criteria for genome-wide significance (P < 2 × 10(-7)). Notably, the majority of genome-wide findings would not have been uncovered via analysis of untreated samples. These results indicate that identifying eQTL after relevant environmental perturbation enables identification of true pharmacogenetic variants.

Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity.

Inhalation of diesel exhaust (DE) at moderate concentrations causes increased airway responsiveness in asthmatics and increased airway resistance in both healthy and asthmatic subjects, but the effect of baseline airway responsiveness and anti-oxidant supplementation on this dynamic is unknown. We aimed to determine if changes in airway responsiveness due to DE are attenuated by thiol anti-oxidant supplementation, particularly in those with underlying airway hyper-responsiveness. Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for 6 days. On the last of these 6 days, participants were exposed for 2 h to either filtered air (FA) or DE (300 μg/m(3) of particulate matter smaller than 2.5 microns). Twenty-six non-smokers were studied under each of three experimental conditions (filtered air with placebo, diesel exhaust with placebo, and diesel exhaust with N-acetylcysteine) using a randomized, double-blind, crossover design, with a 2-week washout between conditions. Methacholine challenge was performed pre-exposure (baseline airway responsiveness) and post-exposure (effect of exposure). Anti-oxidant supplementation reduced baseline airway responsiveness in hyper-responsive individuals by 20% (p = 0.001). In hyper-responsive individuals, airway responsiveness increased 42% following DE compared with FA (p = 0.03) and this increase was abrogated with anti-oxidant supplementation (diesel exhaust with N-acetylcysteine vs. filtered air with placebo, p = 0.85). Anti-oxidant (N-acetylcysteine) supplementation protects against increased airway responsiveness associated with DE inhalation and reduces need for supplement bronchodilators in those with baseline airway hyper-responsiveness. Individuals with variants in genes of oxidative stress metabolism when exposed to DE are protected from increases in airway responsiveness if taking anti-oxidant supplementation.

In vitro airway responses to methacholine challenge following intermittent neonatal CPAP in mice (870.5)

Although continuous positive airway pressure (CPAP) is commonly used in the care of pre‐term infants, its long‐term effects on airway reactivity are largely unknown. In the current study, we investigated whether neonatal CPAP leads to long‐term changes in airway responses to methacholine using the in vitro mouse lung slice preparation. We hypothesized that CPAP treatment during the first week of life would result in a long‐term decrease in airway responsiveness to methacholine. Neonatal mice were exposed to CPAP (6cm H2O) for 3 hours per day for the first 7 postnatal days. Control animals experienced the same conditions as experimental animals only with no CPAP. On days 7 and 21 (2 weeks after CPAP), precision cut lung slices were harvested, and airway responses to increasing doses of methacholine (0.25µM‐8µM) were examined. Contrary to our hypothesis, at both P7 and P21, airways from CPAP exposed mice displayed increased airway reactivity to methacholine challenge when compared to airways from age‐matched control mice. We concluded that CPAP treatment during the early neonatal period may lead to a long‐term increase in airway reactivity.

Inhalation of multi‐walled carbon nanotubes affects lung resistance and compliance and evokes airway hyperreactivity to methacholine in rats (660.1)

The incorporation of carbon nanotubes into new materials has raised concerns about their potential hazards to workers exposed during manufacturing. In animals, following pharyngeal aspiration, i.t. instillation and inhalation exposures to MWCNT, airway inflammation and lung fibrosis have been reported. However, the effects of inhalation of MWCNT on pulmonary function and reactivity to inhaled methacholine (MCh), a bronchoconstrictor, have not been studied. Therefore, we investigated whether inhaled MWCNT affect lung resistance (RL) and dynamic compliance (CDyn), and/or reactivity to inhaled MCh aerosol. Male rats were exposed for 6 h to filtered air or 5 mg/m3 of aerosolized MWCNT (MWNT‐7; Hodogaya Chemical Co.; 20 ‐ 50 walls; median length, 3.86 μm; mean width, 49 nm; mass median aerodynamic diameter, 1.5 μm; particle count aerodynamic diameter mode, ~0.4 μm). Basal RL and CDyn were measured 18 h and 7 d after the end of exposure, and responses to increasing concentrations of MCh were obtained. Eighteen h after exposure basal RL was increased and basal CDyn was decreased; 7 d after exposure basal RL and CDyn were not changed. Reactivity to MCh (RL) was increased and CDyn responses were decreased at 18 h but not 7 d after exposure. The results indicate that lung function and airway reactivity changes occur acutely, but that these changes subside over time following a single MWCNT inhalation exposure.Grant Funding Source: Supported by NIOSH

Refractoriness to inhaled mannitol 3 hours after allergen challenge

BackgroundA positive response to indirect airway challenges (eg, mannitol) that cause release of mast cell mediators causes refractoriness to a repeat exposure to the same or different indirect stimulus that lasts for at least several hours. Allergen challenge causes increased response to methacholine measured at 3 hours. ObjectiveTo compare allergen-induced changes in airway response to methacholine and mannitol 3 hours after completion of an allergen challenge. MethodsTen atopic patients with asthma completed a randomized clinical trial. The provocation concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV1) was measured 24 hours before and 3 hours after a standard allergen challenge. The provocation dose of mannitol causing a 15% decrease in FEV1 was also measured 24 hours before and 3 hours after allergen challenge. The allergen challenges were separated by 7 to 14 days. ResultsThe allergen-induced early responses, expressed as the maximum (SD) percent decrease in FEV1, were 29.7% (11.1%) and 27.8% (7.6%) on the methacholine and mannitol days, respectively. Airway response to methacholine increased significantly after allergen challenge (P = .02). By contrast, the airway response to mannitol was reduced by almost a doubling dose (P = .02) after allergen. ConclusionThree hours after allergen challenge at a time when the airways are more responsive to methacholine, there is a significant refractoriness to the indirect stimulus mannitol. Trial Registrationclinicaltrials.gov Identifier: NCT01699594

Assessment of bronchial responsiveness on exposure to isometric exercise during different phases of menstrual cycle: A pilot study

The present study was planned to assess the effects of gonadal steroids (estrogen and progesterone) on bronchial responsiveness, before and after handgrip exercise, during different phases of menstrual cycle. In this study, 30 healthy (25-40 years), non-athletic, adult female volunteers were studied. The various pulmonary function parameters (FVC, FEV1, PEFR, FEF 25-75%) were recorded with a spirometer under resting conditions and then within five minutes of cessation of isometric exercise. Recordings were taken during the Menstrual phase (MP), Proliferative phase (PP), and Luteal phase (LP) of menstrual cycle and were confirmed by plasma levels of estrogen and progesterone. The oral temperature was recorded during each phase of the menstrual cycle. Under resting conditions, the above-mentioned parameters did not reveal significant differences during the three phases. A significant fall was observed only in the Peak Expiratory Flow Rate (PEFR) during all the phases after handgrip, but there was a non-significant decline in the other parameters. By this study we conclude that the physiological changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway responsiveness before and after the handgrip test. The general fall seen in the pulmonary parameters could be due to fatigue or psychic factors.

The effect of rhinovirus on airway inflammation in a murine asthma model

PurposeThe aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection.MethodsBALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection.ResultsRV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05).ConclusionOur findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

S131 Identifying Occupational Asthma Among a Cohort of Cleaners in the North East England

IntroductionWe have demonstrated a prevalence of asthma of 14% in a survey of 1400 UK hospital and university cleaners, and an estimated incidence of asthma of 3.3/1000 person-years. 26% of...

Pathology and airway reactivity changes in Galectin-7 transgenic mice

Pathology and airway reactivity changes in Galectin-7 transgenic mice

Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation

Asthma in obese subjects is poorly understood, and these patients are often refractory to standard therapy. We sought to gain insights into the pathogenesis and treatment of asthma in obese subjects by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness (AHR), and markers of asthmatic inflammation. We performed a prospective study of (1) asthmatic and nonasthmatic patients undergoing bariatric surgery compared at baseline and (2) asthmatic patients followed for 12 months after bariatric surgery. We studied 23 asthmatic and 21 nonasthmatic patients undergoing bariatric surgery. At baseline, asthmatic patients had lower FEV(1) and forced vital capacity and lower numbers of lymphocytes in bronchoalveolar lavage fluid. After surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score, 1.55 to 0.74; P < .0001) and asthma quality of life (4.87 to 5.87, P < .0001). Airways responsiveness to methacholine improved significantly (methacholine PC(20), 3.9 to 7.28, P = .03). There was a statistically significant interaction between IgE status and change in airways responsiveness (P for interaction = .01). The proportion of lymphocytes in bronchoalveolar lavage fluid and the production of cytokines from activated peripheral blood CD4(+) T cells increased significantly. Bariatric surgery improves AHR in obese asthmatic patients with normal serum IgE levels. Weight loss has dichotomous effects on airway physiology and T-cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.

Effect of San’ao Decoction (三拗汤) on the airway inflammation and hyperresponsiveness in a murine model of lipopolysaccharide-enhanced asthma

San'ao Decoction (, SAD), as a representative Chinese medicine (CM) formula, was chosen to evaluate the effect of airway inflammation and hyperresponsiveness on the lipopolysaccharide (LPS) enhanced asthma model. The asthma model was reproduced in the Balb/C mice sensitized by ovalbumin (OVA), challenged by OVA and LPS. After Balb/C mice's administration of a dose (0.0024 g/kg) of dexamethasone acetate, and three doses (2.2 g/kg, 4.4 g/kg and 8.8 g/kg) of SAD, airway inflammation and responsiveness were observed. The airway inflammation was detected by counting bronchoalveolar lavage fluid (BALF) cells and lung histopathology. Also, differential expressions of interferon-r (IFN-γ), interleukin-4 (IL-4), and IL-5 in the supernatants of BALF were examined. The changes in airway responsiveness indicated by lung resistance (R(L)) and stimulated by acetylcholine (Ach) were determined. Small-dose SAD hardly inhibit airway inflammation or hyperresponsiveness in the LPS-enhanced asthma, while medium-dose and high-dose SAD significantly inhibited the airway hyperresponsiveness, and to some extent, reduced airway inflammation. Meanwhile, the small-dose, medium-dose, and high-dose SAD promoted Th1-type cytokines (IFN-γ) and reduced Th2-type cytokines (IL-4, IL-5) to different extents, which led to a Th1/Th2 balance. SAD has a good therapeutic effect on airway hyperresponsiveness in the LPS-enhanced asthma model, but its definite influence on airway inflammation is not remarkable.

Airway reactivity to inhaled spasmogens 18-24 h after antigen-challenge in sensitized anaesthetized guinea-pigs.

The anaesthetized allergic guinea-pig was used to assess changes in airway reactivity to four different inhaled spasmogens: methacholine, 5-hydroxytryptamine (5-HT), histamine and the thromboxane A2 mimetic, 9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha (U-46619). Reactivity was determined 18 to 24 h after challenge of ovalbumin-sensitized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensitivity to the spasmogen was assessed from the concentration-response curve for the increase in pulmonary inflation pressure (PIP) in ovalbumin- and saline-challenged sensitized animals. When methacholine, 5-HT or histamine were the spasmogens there was no hyper-reactivity. The geometric mean EC50 values (i.e. the concentrations inducing half the maximum effect) obtained from the dose-response curves for methacholine (73 (42-129) and 94 (66-134) micrograms mL-1), 5-HT (1.5 (0.81-3.03) and 1.1 (0.51-2.24 micrograms mL-1) and histamine (39 (21-75) and 72 (32-162) micrograms mL-1) did not differ significantly (P > 0.05) between saline- and ovalbumin-challenged animals, respectively. However, when U-46619 was the spasmogen, ovalbumin-induced airway hyper-reactivity was observed as a leftwards shift of the concentration-response curve and the EC50 value for ovalbumin-challenged animals (8.1 (5.1-13) ng mL-1) was significantly (P < 0.05) less than the value for control animals (39 (21-75) ng mL-1). Our findings suggest that airway hyper-reactivity is not 'non-specific', but instead depends on the chosen spasmogen. The absence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spasmogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because ozone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine and agonists at muscarinic receptors is regularly seen in man, the anaesthetized guinea-pig might not be the ideal model for assessing airway hyper-reactivity after antigen challenge and its modification by anti-asthma drugs.

Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma

PurposeSynthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question.MethodsWe prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid.ResultsRANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-γsynthesis nor airway responsiveness in either control or D. farinae mice.ConclusionRSV infection did not induce more RANTES in a murine model of asthma than in control mice.