Increased Airway Responsiveness Research Articles

Effect of Perinatal secondhand tobacco smoke exposure on in vivo and intrinsic airway structure/function in non-human primates

Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in responsiveness. Pregnant rhesus monkeys were exposed to filtered air (FA) or SHS (1 mg/m 3 total suspended particulates) for 6 h/day, 5 days/week starting at 50 days gestational age. The mother/infant pairs continued the SHS exposures postnatally. At 3 months of age each infant: 1) had in vivo lung function measurements in response to inhaled methacholine, or 2) the right accessory lobe filled with agarose, precision-cut to 600 μm slices, and bathed in increasing concentrations of methacholine. The lumenal area of the central airway was determined using videomicrometry followed by fixation and histology with morphometry. In vivo tests showed that perinatal SHS increases baseline respiratory rate and decreases responsiveness to methacholine. Perinatal SHS did not alter intrinsic airway responsiveness in the bronchi. However in respiratory bronchioles, SHS exposure increased airway responsiveness at lower methacholine concentrations but decreased it at higher concentrations. Perinatal SHS did not change eosinophil profiles, epithelial volume, smooth muscle volume, or mucin volume. However it did increase the number of alveolar attachments in bronchi and respiratory bronchioles. In general, as mucin increased, airway responsiveness decreased. We conclude that perinatal SHS exposure alters in vivo and intrinsic airway responsiveness, and alveolar attachments.

Childhood Asthma and Increased Airway Responsiveness

Asthma is associated with increased airway responsiveness (AR), but the age when this relationship becomes established is not clear. The present study tested the hypothesis that the association between increased AR and asthma is established after 1 month of age. To relate AR in infancy to asthma in childhood. As part of a birth cohort study, AR was determined at 1 (early infancy), 6 (mid-infancy), and 12 months of age (late infancy). At 11 years of age (childhood), AR and the presence of asthma symptoms were determined. Of the 253 study subjects enrolled, AR was determined in 202 in early infancy, 174 in mid-infancy, 147 in late infancy, and 176 in childhood. Increased AR in late infancy, but not in early or mid-infancy, was associated with increased wheeze at 11 years of age (P = 0.016). Increased AR in infancy persisted into childhood in association with male gender, early respiratory illness, and maternal smoking and asthma. Among the 116 subjects assessed in late infancy and childhood, recent wheeze was present in 35% of children with increased AR at both ages, 13% with increased AR in childhood only, 12% for those with increased AR in late infancy only, and 0% for those who did not have increased AR at either age (P = 0.023); the proportions of children with diagnosed asthma in the corresponding groups were 27, 20, 12, and 0% (P = 0.038). The association between increased infantile AR and childhood asthma emerges at the end of the first year of life.

Vγ1+ T Cells and Tumor Necrosis Factor-Alpha in Ozone-Induced Airway Hyperresponsiveness

gammadelta T cells regulate airway reactivity, but their role in ozone (O3)-induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of gammadelta T cells in O3-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total gammadelta T cells or specific subsets of gammadelta T cells, were exposed to 2.0 ppm of O3 for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored. Exposure of C57BL/6 mice to O3 resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-delta(-/-) mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of gammadelta T cells in wild-type mice suppressed O3-induced AHR without influencing airway inflammation or epithelial damage. Depletion of Vgamma1+, but not of Vgamma4+ T cells, reduced O3-induced AHR, and transfer of total gammadelta T cells or Vgamma1+ T cells to TCR-delta(-/-) mice restored AHR. After transfer of Vgamma1+ cells to TCR-delta(-/-) mice, restoration of AHR after O3 exposure was blocked by anti-TNF-alpha. However, AHR could be restored in TCR-delta(-/-)mice by transfer of gammadelta T cells from TNF-alpha-deficient mice, indicating that another cell type was the source of TNF-alpha. These results demonstrate that TNF-alpha and activation of Vgamma1+ gammadelta T cells are required for the development of AHR after O3 exposure.

Occupational asthma caused byArabidopsis thaliana: a case of laboratory plant allergy

A 36-yr-old male never-smoker with an 8-yr history of hay fever but no past history of asthma undertook a 3-yr research project involving the plant Arabidopsis thaliana. The subject was based in a small laboratory with an attached growing room. After 30 months of research, he began to develop breathlessness within 5-10 min of entering the laboratory. Initial investigations confirmed asthma with airflow obstruction (forced expiratory volume in one second (FEV(1))/forced vital capacity was 3.01/4.75 L; predicted values were 3.67/4.43 L) and increased airway responsiveness. Serial peak expiratory flow measurements showed a work-related pattern. A supervised workplace challenge test led to a fall in FEV(1) from the baseline value of 3.10 L to 1.95 L within 20 min of entering the growing room. Skin-prick solutions were prepared from Arabidopsis leaves and flower heads; positive 4-mm responses were obtained to the flower heads (i.e. to the pollen). Arabidopsis is a member of the Brassicaceae family. It is used extensively in plant biology research as its genome is small, has been fully sequenced and is easily manipulated. The present article represents the first reported case of occupational asthma due to Arabidopsis thaliana.

Liver X Receptor Agonists Increase Airway Reactivity in a Model of Asthma via Increasing Airway Smooth Muscle Growth

The liver X receptors (LXRalpha/beta) are orphan nuclear receptors that are expressed in a large number of cell types and have been shown to have anti-inflammatory properties. Nuclear receptors have previously proved to be amenable targets for small molecular mass pharmacological agents in asthma, and so the effect of an LXR ligand was assessed in models of allergic airway inflammation. LXR agonist, GW 3965, was profiled in rat and mouse models of allergic asthma. In the Brown Norway rats, GW 3965 (3-30 mg/kg) was unable to reduce the bronchoalveolar lavage eosinophilia associated with this model and had no impact on inflammatory biomarkers (eotaxin and IL-1beta). The compound did significantly stimulate ABCA-1 (ATP-binding cassette A1) mRNA expression, indicating that there was adequate exposure/LXR activation. In the mouse model, the LXR ligand surprisingly increased airway reactivity, an effect that was apparent in both the Ag and nonchallenged groups. This increase was not associated with a change in lung tissue inflammation or number of mucus-containing cells. There was, however, a marked increase in airway smooth muscle thickness in both treated groups. We demonstrated an increase in contractile response to exogenous methacholine in isolated airways taken from LXR agonist-treated animals compared with the relevant control tissue. We corroborated these findings in a human system by demonstrating increased proliferation of cultured airway smooth muscle. This phenomenon, if evidenced in man, would indicate that LXR ligands may directly increase airway reactivity, which could be detrimental, especially in patients with existing respiratory disease and with already compromised lung function.

Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood

Background:Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on...

Brain-derived neurotrophic factor enhances histamine-induced airway responses and changes levels of exhaled nitric oxide in guinea pigs in vivo

The neurotrophin brain-derived neurotrophic factor (BDNF) occurs in elevated levels during airway inflammation, including asthma and hypoxic lung injury, and has been suggested to be associated with airway hyperresponsiveness in these conditions. The aim of the present study was to examine whether airway responses to histamine challenge and levels of exhaled nitric oxide (NO) in vivo might be altered upon BDNF treatment. Pulmonary resistance, lung compliance, insufflation pressure, and levels of exhaled NO were measured in anaesthetized guinea pigs exposed to BDNF prior to challenge with histamine and with intact or inhibited endogenous NO production. BDNF pretreatment significantly enhanced histamine-evoked increase in pulmonary resistance and insufflation pressure, as well as the decrease in lung compliance. BDNF markedly accentuated the reduction in exhaled NO following histamine challenge. In animals with inhibited endogenous NO production BDNF induced a significantly earlier histamine-evoked increase in airway responses. The present data show that BDNF can induce an augmentation of histamine-evoked airway responses and reduce levels of NO in exhaled air in vivo. Endogenous NO seems to exert a braking action on BDNF-induced enhancement of airway responses and a reduced ability to release NO may be one mechanism for increased airway response during elevated BDNF levels. Taken together this indicates that BDNF may be of importance for airway hyperresponsiveness in vivo. The interaction between BDNF and airway NO formation, and its relation to airway responses, merit further investigation.

The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model.

Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus and electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Herein we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than did control mice, although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-gamma, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens.

Competitive swimmers with allergic asthma show a mixed type of airway inflammation: Fig. 1—

To the Editors: Elite swimmers are at increased risk of asthma 1. This has been attributed to airway inflammation and increased airway responsiveness induced by high-intensity long-term exercise and repeated exposure to the chlorine-rich atmosphere in swimming pools during training and competition 2, 3. Recently, increased levels of leukotriene (LT)B4 in exhaled breath condensate and normal exhaled nitric oxide fraction ( F eNO) levels have been reported in five elite swimmers, suggesting possible underlying neutrophilic airway inflammation 4. Previous analysis of induced sputum in nonasthmatic elite swimmers showed increased proportion of eosinophils and neutrophils compared with healthy controls 3. We aimed to characterise the airway inflammation in competitive asthmatic swimmers. Athletes from the FC Porto main swimming team and 20 nonathlete asthmatics were recruited; participants gave informed consent. Subjects were classified by their asthma and training status as asthmatic swimmers (n = 6, two female, aged 17±2 yrs, competing 8±3 yrs, training 16±4 h·week−1), asthmatics (n = 20, eight female, aged 14±3 yrs) and swimmers (n = 20, six female, aged 17±2 yrs, competing 8±3 yrs, training 17±3 h·week−1). All asthmatics and nine (45%) of the swimmers were atopic according …

Asthma, allergy, the athlete and the Olympics

As the 2008 Summer Olympics in Beijing approach, both the general public and health care professionals are gaining interest in the potential health implications of sport. When asthma and allergy are present in athletes, this may affect their performance and achievements and justify the special attention of health care professionals who specialize in taking care of top athletes. However, the impact of allergy and asthma on sport and exercise goes further than just top athletes. The Editors of Allergy decided that in this issue they would focus the attention of allergy and asthma specialists by presenting a series of articles on the relationship between sport, asthma and allergy in the hope that an increased awareness of these problems would be highlighted not only for sports medicine doctors but also for all practicing allergists. Exercise-induced asthma (EIA) is a general concern for growing children and adolescents. In most international guidelines, one of the main objectives of treating asthma during childhood is for the child to be able to master EIA. Also among athletes, and especially elite athletes, EIA and bronchial hyperresponsiveness (BHR) have become major problems with regard to the correct diagnosis and to treatment. EIA is increasingly common among the top athletes of several different types of sport. Traditionally this has been reported mainly in athletes competing in endurance sports in cold climates, especially among crosscountry skiers (1, 2) and swimmers (3, 4), but also among endurance athletes in summer sports (5). A surprisingly high prevalence of asthma (56%) diagnosed by the reversibility of lung function to inhaled s2-agonists (56%) was reported among professional Canadian football players (6). The prevalence of EIA among top athletes has increased over the past decades. Weiler et al. reported 11% prevalence of EIA among American athletes participating in the 1984 Summer Olympic Games (7) and an increase to a prevalence of more than 20% was noticed among American participants in the 1996 Summer Olympic Games in Atlanta (8).

Pharmacodynamic and pharmacokinetic characterisation of RBx 7796: a novel 5-lipoxygenase inhibitor

RBx 7796, a 5-lipoxygenase inhibitor, was evaluated in in vivo efficacy models, in vitro ADME and in vivo pharmacokinetic models. RBx 7796 was evaluated for inhibition of 5-lipoxygenase enzyme and release of LTB4 from isolated rat and human neutrophils. RBx 7796 was tested in allergic bronchoconstriction model in Balb/c mice and LPS induced airway hyperreactivity model in rats. RBx 7796 was evaluated for metabolic stability in liver microsomes and cytochrome P450 inhibition potential. Pharmacokinetic profile of RBx 7796 was also determined in rat and dog. RBx 7796 inhibited 5-lipoxygenase enzyme and inhibited release of LTB4 from neutrophils. RBx 7796 also inhibited early and late airway reactivity following allergen challenge in mouse model. LPS induced increase in airway reactivity was blocked by RBx 7796. Compound was found to be stable in liver microsomes and devoid of major cytochrome P450 inhibition potential. The oral bioavailability of RBx 7796 in rat and dog was 83 % and 47 %, respectively. Following repeated daily administration, compound did not exhibit any sign of accumulation and/or tendency to induce its own metabolism. The results suggest that RBx 7796 is an inhibitor of 5-lipoxygenase enzyme that is orally efficacious in two different models of airway reactivity. The molecule also demonstrated acceptable pharmacokinetic profile warranting further development.

Indoleamine 2,3-dioxygenase–dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive effects on asthma manifestations and (2) whether tryptophan depletion or generation of its downstream metabolites is involved. Ovalbumin (OVA)-sensitized and OVA-challenged BALB/c mice that display increased airway responsiveness to methacholine, serum OVA-specific IgE levels, bronchoalveolar eosinophilia, and TH2 cytokine levels were used as a model of allergic asthma. Sensitized mice received subcutaneous optimal (1 mg) or suboptimal (100 microg) OVA immunotherapy. Inhibition of IDO by 1-methyl-DL-tryptophan during immunotherapy, but not during inhalation challenge, partially reversed the suppressive effects of immunotherapy on airway eosinophilia and TH2 cytokine levels, whereas airway hyperresponsiveness and serum OVA-specific IgE levels remained suppressed. Administration of tryptophan during immunotherapy failed to abrogate its beneficial effects toward allergic airway inflammation. Interestingly, administration of tryptophan or its metabolites, kynurenine, 3-hydroxykynurenine, and xanthurenic acid, but not 3-hydroxyanthranilinic acid, quinolinic acid, and kynurenic acid, during suboptimal immunotherapy potentiated the reduction of eosinophilia. These effects coincided with reduced TH2 cytokine levels in bronchoalveolar lavage fluid, but no effects on IgE levels were detected. During immunotherapy, the tryptophan metabolites kynurenine, 3-hydroxykynurenine, and xanthurenic acid generated through IDO contribute to tolerance induction regarding TH2-dependent allergic airway inflammation.

Paternal Asthma, Mold Exposure, and Increased Airway Responsiveness Among Children With Asthma in Costa Rica

Little is known about the determinants of airway hyperresponsiveness (AHR) among children with asthma in Hispanic America. We examined the relations among selected familial and environmental factors, markers of allergy, spirometric measures of lung function, and AHR in a cross-sectional study of 403 Costa Rican children with asthma between the ages of 6 and 14 years. Study participants completed a protocol that included questionnaires, spirometry, measurements of serum total and allergen-specific IgE, peripheral blood eosinophil count, and body mass index, and the assessment of airway responsiveness to methacholine (ie, a methacholine challenge test [MCT]). AHR to MCT was defined as the provocative dose of methacholine causing a 20% fall in FEV(1). Linear regression was used for the univariate and multivariate analyses. Of the 403 asthmatic children who underwent an MCT, 350 (86.8%) had AHR to methacholine. In a multivariate analysis, paternal asthma (p = 0.004), parental report of mold/mildew in the child's home (p = 0.04), FEV(1)/FVC ratio (p < 0.0001), and a positive IgE response to Der p 1 (p = 0.008) were significantly associated with AHR among Costa Rican children with asthma. Our results suggest that paternal asthma and environmental exposure to mold/mildew are strong determinants of AHR in Costa Rican children with asthma. FEV(1)/FVC ratio may be a useful measure of AHR (a marker of asthma severity) among Costa Ricans and other Hispanic Americans for whom reference values for FEV(1) are not currently available.

Nerve growth factor enhances neurokinin A-induced airway responses and exhaled nitric oxide via a histamine-dependent mechanism

The neurotrophin nerve growth factor (NGF) is elevated in serum and locally in the lung in asthmatics and has been suggested to evoke airway hyperresponsiveness. The aim of this study was to explore mechanisms behind NGF-evoked changes in airway responsiveness. We studied if NGF could evoke increased airway responsiveness to tachykinins, such as neurokinin A (NKA), in a similar way as for histamine and, if so, whether an NGF-evoked increase in NKA airway responsiveness could involve a histamine receptor-dependent mechanism. Contractile responses to cumulative doses of histamine or NKA were studied in guinea-pig tracheal rings in vitro in organ baths. Furthermore, insufflation pressure (IP), pulmonary resistance, lung compliance and exhaled NO (FeNO) were measured in vivo in anaesthetised guinea-pigs challenged with histamine or NKA. NGF pre-treatment in vitro increased the contractile response evoked by histamine, but not by NKA, in tracheal rings. NGF pre-treatment in vivo increased IP, pulmonary resistance and levels of FeNO, and further decreased lung compliance, upon histamine and NKA challenge. The NGF-evoked enhancement of IP, pulmonary resistance, lung compliance as well as FeNO in response to NKA was reversed by the histamine receptor antagonist mepyramine. We suggest that NGF can induce an increase in tachykinin-evoked airway responses and NO formation via a histamine receptor-dependent pathway. This points to an important role for the mast cell in neurotrophin-evoked airway hyperresponsiveness and changes in exhaled NO.

Airway responses to salbutamol after exposure to chemical warfare

Increased airway responsiveness to beta-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to beta-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare. The threshold concentrations of inhaled salbutamol required for a 20% change in FEV(1) as PC(20), or a 35% change in specific airway conductance (sGaw) as PC(35) were measured in 22 persons exposed to chemical warfare and 15 normal control subjects. In 11 of the 22 subjects PC(20) salbutamol could be measured and in 15 of the 22 subjects PC(35) salbutamol could be measured. This group of patients was the responder group (PC(20) = 10.79 and PC(35) = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC(20) = 237.68 and PC(35) = 88.72 mg/L, P < 0.001). There was a significant correlation between FEV(1) and PC(20) salbutamol (r = 0.815, P < 0.001). These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects

Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. Twenty-three obese (BMI (body mass index) > or =30 kg m(-2)) and 26 non-obese (BMI <30 kg m(-2)) non-asthmatic subjects, aged between 18 and 70 years. High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P=0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P=0.03). Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

Airway responsiveness: associated features in infants with recurrent respiratory symptoms

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.

Age differences in cholinergic airway responsiveness in relation with muscarinic receptor subtypes

Children seem more susceptible to increased airway reactivity than adults. Such an age-dependent discrepancy in airway reactivity may involve different airway smooth muscle functions. Therefore, we compared the in vivo and in vitro responsiveness of airway smooth muscles between two age groups of animals. Rats of 6 and 21 weeks old were challenged in vivo with acetylcholine (ACh) infused intravenously and airway resistance ( R aw) was measured. Tracheal muscle was also isolated and the isometric force developed to ACh or KCl was measured. Furthermore, the level of genes encoding muscarinic receptor subtypes (M 1–3) and acetylcholinesterase (AChE) expressed in the tracheal muscle was determined by RT-PCR. In results, the basal R aw was similar in the two age groups. The R aw at each ACh dose was significantly greater in young rats than older rats ( p < 0.05, n = 22–27). Tracheal muscles from young rats were more sensitive to ACh than older rats ( p < 0.05, n = 20–21), while receptor-independent muscle contraction to KCl was greater in older rats ( p < 0.05, n = 10–19). Genes encoding AChE, M 2 and M 3 muscarinic receptors were more highly expressed in the tracheal muscles from young than older rats ( p < 0.05, n = 4–6). In conclusion, airway smooth muscle in young rat is more sensitive to cholinergic stimulation in vivo and in vitro compared to older rats, which may be due to a higher expression of M 2 and M 3 muscarinic receptors in airway smooth muscle.

Exercise while Breathing High Ambient Auto/Truck Emission causes Decreased Lung Function in Non-Asthmatic Subjects

Chronic inhalation of internal combustion derived ultrafine particulate matter (PM1) is associated with airway inflammation and decreased resting lung function and may be causal to the reported high prevalence of exercise-induced asthma (EIA) in ice rink athletes. PURPOSE: To evaluate effects of 30 min of high [PM1] exposure exercise on lung function in non-asthmatic subjects. METHODS: Twelve non-asthmatic male college athletes performed random order exercise for 30 min while breathing either low (7,380±1650 particles/cm3) or high (252,300±74,200 particles/cm3) auto/truck emission PM1. Lung function was measured before and after exercise. RESULTS: Resting lung function was above age/gender/height predicted values (110, 117, 120 percent predicted for FVC, FEV1, FEF 25–75; respectively). For low PM1 exercise, no change in FVC, FEV1, or FEF25–75 was noted. However, for high PM1 exercise statistically significant falls in FEV1 and FEF25–75 were found (3%1 (60 ml) and 6% (400 ml) for FEV1 and FEF25–75, respectively p<0.005). Change in FEV1 and FEF25–75 were significantly correlated to [PM1] (R=−0.57, p =0.004 and R=−0.63, p=0.001, respectively). For every 10,000/cm3 increase in PM1 a decrease of 5.3 ml in FEV1 and 26 ml in FEF25–75 occurred. CONCLUSION: Although the decrease in lung function after high PM1 exercise in non-asthmatic subjects is statistically significant, it was not clinically significant. Chronic inhalation of PM1 during exercise may cause increased airway reactivity; exercise in high ambient pollutant areas should be minimized. This study provides support for the notion that exposure to exhaust fumes from hourly ice resurfacing by fossil-fueled machines is responsible for the high observed prevalence of EIA in ice rink athletes.

Advances in environmental and occupational disorders 2006

In 2006, there continued to be significant contributions to the Journal in the area of environmental and occupational allergy. In addition to very strong clinical observations, there were a number of studies that examined the effect of environmental agents on cellular and molecular processes in allergy, and molecular approaches were also used in investigations of allergen structure and biology. The Journal also received a number of very strong epidemiologic studies examining several aspects of environmental and occupational allergy. Thus, this particular area of our specialty thrives as a result of clinical, mechanistic, epidemiologic, and translational observations. This article reviews a number of these papers presented in the Journal in 2006.