A genome-wide screen for asthma-associated quantitative trait loci in a mouse model of allergic asthma.
Asthma is the most common illness of childhood, affecting one child in seven in the UK. Asthma has a genetic basis, but genetic studies of asthma in humans are confounded by uncontrolled environmental factors, varying penetrance and phenotypic pleiotropy. An animal model of asthma would offer controlled exposure, limited and consistent genetic variation, and unlimited size of sibships. Following immunization and subsequent challenge with ovalbumin, the Biozzi BP2 mouse shows features of asthma, including airway inflammation, eosinophil infiltration and non-specific bronchial responsiveness. In order to identify genetic loci influencing these traits, a cross was made between BP2 and BALB/c mice, and a genome-wide screen carried out in the F2progeny of the F1intercross. Five potentially linked loci were identified, four of which corresponded to human regions of syntenic homology that previously have shown linkage to asthma-associated traits. (+info)
Histamine release upon adenosine 5'-monophosphate (AMP) nasal provocation in allergic subjects.
BACKGROUND: Nasal provocation with adenosine 5'-monophosphate (AMP) elicits nasal symptoms in subjects with rhinitis. Histamine released from mast cells may play a part in AMP induced nasal responses. METHODS: Symptoms of rhinitis were recorded and histamine release in the fluid obtained by nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo instillations was measured in nine subjects with allergic rhinitis and nine non-allergic controls in a double blind, randomised, placebo controlled study. RESULTS: No symptoms or significant increases in histamine were observed after GMP and placebo challenge. Significantly higher levels of histamine were seen in the nasal lavage fluids of allergic subjects following AMP challenge than in nonallergic controls, the median (range) histamine concentration increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels was seen in the non-allergic subjects in whom the median histamine concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge. CONCLUSIONS: AMP elicits an immediate rise in histamine levels in the nasal lavage fluid of allergic subjects compared with non-allergic individuals. These findings indicate that the exaggerated nasal response to adenosine may reflect mast cell priming in vivo, thus supporting its application as a potential new marker of allergic inflammation. (+info)
Nasal patency and lavage biomarkers in relation to settled dust and cleaning routines in schools.
OBJECTIVES: This study determined the relations between settled dust and cleaning routines in classrooms on one hand, and nasal symptoms, nasal cavity dimensions, and the concentration of selected biomarkers of inflammation in nasal lavage on the other. METHODS: Measurements of settled dust via standardized vacuum cleaning and an investigation of the cleaning routines were performed in 12 randomly selected primary schools in the municipality of Uppsala. Clinical examinations including acoustic rhinometry and nasal lavage were performed in the school environment among 279 school personnel working in the main buildings of the schools. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in the lavage fluid. The relationships between the medical and hygienic data were analyzed both bivariately and with a multiple regression model controlling for age, gender, smoking, atopy, room temperature, and urban vicinity of the school. RESULTS: The amount of settled dust was positively related to subjective nasal obstruction and smaller nasal cavity dimensions measured with acoustic rhinometry. The noses were less patent, and the levels of ECP or lysozyme in the lavage were increased for the subjects in schools with a lower frequency of floor mopping, a lower frequency of desk cleaning, and where wet mopping was used. CONCLUSIONS: Our results indicate that the actual dust levels in Swedish classrooms can affect the occurrence of nasal obstruction among school personnel. A beneficial effect on the clinical signs of the nasal mucosa was observed for a higher frequency of both floor mopping and desk cleaning, whereas the use of wet mopping seemed disadvantageous in comparison with dry mopping. These findings illustrate the need for adequate cleaning procedures to minimize the environmental effects on the airway mucosa. (+info)
Intranasal challenge with aspirin in the diagnosis of aspirin intolerant asthma: evaluation of nasal response by acoustic rhinometry.
BACKGROUND: Nasal provocation tests with lysine-aspirin have recently been introduced for assessment of aspirin intolerant asthma. A study was undertaken to evaluate the usefulness of acoustic rhinometry, a new non-invasive technique, in the diagnosis of aspirin intolerant asthma/rhinitis. METHODS: Fifteen patients with aspirin intolerant asthma/rhinitis (nine women, mean (SD) age 54.7 (14) years), eight patients with aspirin tolerant asthma/rhinitis (three women, mean (SD) age 52.6 (7.8) years), and eight healthy subjects (two women, mean (SD) age 32.5 (9.7) years) were studied. All subjects were challenged with saline (0.9% NaCl) and 25 mg lysine acetylsalicylic acid (L-ASA) instilled into each nostril of the nose on two separate days. The clinical response was evaluated based on nasal symptoms (sneezes, itching, secretion and blockage). The nasal response was measured by acoustic rhinometry. Symptoms and rhinometry curves were recorded at 10 minute intervals for three hours, one hour before challenge and two hours after challenge. RESULTS: L-ASA challenge induced a significant increase in symptoms in patients with aspirin intolerant asthma/rhinitis. No differences in the clinical response were detected in those with aspirin tolerant asthma/rhinitis or healthy subjects. L-ASA challenge induced a significant decrease in nasal volume measured by acoustic rhinometry in aspirin intolerant patients. No differences were detected between the challenges in aspirin tolerant patients. If a 25% decrease in nasal volume is taken as the cut off point, the specificity of the test was 94% and the sensitivity reached 73%. The nasal challenge was well tolerated by all subjects. CONCLUSION: Acoustic rhinometry may be used to study the nasal response to L-ASA. Nasal challenge with L-ASA is safe and can be used as a diagnostic test even in asthmatic patients with severe bronchial obstruction. (+info)
Airway reactivity and exhaled NO following swine dust exposure in healthy volunteers.
Short-time exposure to swine dust causes an intense inflammation of upper and lower airways and induces increased bronchial responsiveness to methacholine in previously non-exposed healthy volunteers. The objective to this study was to investigate the nasal inflammatory response and mucosal reactivity to swine dust exposure and whether nitric oxide metabolism is involved in the inflammatory process. Nitric oxide in expired air, nasal histamine test (NH), nasal lavage (NAL) and bronchial histamine challenges were studied before and after a 3 h exposure to swine dust in a swine confinement building in 17 non-smoking healthy subjects not previously exposed to farm dust. To detect any interference between NAL and NH, the subjects were divided into two groups: in group 1, NAL was performed after NH and in group 2, NAL preceded NH. Nasal histamine response increased significantly in group 1, but not in group 2 (P=0.012). Albumin levels in NAL were higher before as well as after dust exposure in group 1 compared to group 2 (P=0.036 and 0.015 respectively). Bronchial histamine responsiveness increased following exposure (P= 0.045). Nitric oxide in expired air decreased following bronchial histamine challenge at baseline (P=0.013) but was otherwise unaltered. Short-time exposure to swine dust increases non-specific reactivity of both nose and bronchi. Nasal lavage procedure interferes with nasal histamine test when performed with connection to each other. The inflammatory reaction may involve NO metabolism. (+info)
Nasobronchial relationship after cold air provocation.
Provocation with cold air in the nose causes broncho-obstruction while warm air causes bronchodilation in patients with asthma, but not in healthy subjects. These findings have suggested the existence of a nasobronchial reflex. The present study aimed to block this effect and evaluate the mechanisms underlying the effect on lung function after cold stimulation of the nose. Lung function, as measured with specific conductance and forced expiratory flow, was reduced after cold stimulation of the nose, but this effect could not be blocked by anesthetizing the nose or by inhaling an anti-cholinergic drug before the provocation. These results confirm the presence of a nasobronchial relationship, but not of a nasobronchial reflex. (+info)
Comparison of cedar pollen-induced allergic rhinitis in passively and actively sensitized guinea pigs.
We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized. (+info)
Effects of olopatadine hydrochloride on the increase of histamine and peptide-leukotrienes concentrations in nasal lavage fluid following the antigen-antibody reaction in actively sensitized guinea pigs.
To investigate the mechanism for the amelioration by olopatadine hydrochloride (olopatadine) of allergic rhinitis, we determined its effects on the increase of chemical mediator concentrations in nasal lavage fluid following the intranasal antigen challenge in guinea pigs actively sensitized with DNP-Ascaris. The concentrations of histamine and peptide-leukotrienes increased 10 min after the challenge. Olopatadine at 10 mg/kg (p.o.) significantly prevented the increase of histamine and tended to inhibit the increase of peptide-leukotrienes. The inhibition by olopatadine of the nasal symptoms seems to involve the inhibitory effect on the releases of histamine and, possibly, p-LTs into the nasal cavity. (+info)