Siberian hamster: a new indoor source of allergic sensitization and respiratory disease.

BACKGROUND: The identification of 'unknown' allergic sensitizations may determine the prognosis and treatment of patients with respiratory airway disease. Currently, the presence in homes of 'exotic' animals as pets is increasing. In this article the Siberian hamster or dwarf hamster (Phodopus sungorus) was identified as a new indoor source of aeroallergens and respiratory disease. METHODS: The subjects were six outpatients who were treated for asthma and rhinitis. Siberian hamster hair extract was prepared with a standard wt/vol method, and patients were skin-prick tested with the extract. Serum-specific immunoglobulin (Ig)E against the Siberian hamster, common hamster (Cricetus cricetus) and golden hamster (Mesocricetus auratus) was determined. IgE-immunoblotting was also performed for all six sera. Specific bronchial challenge was carried out with the Siberian hamster extract. RESULTS: Skin prick tests (SPT) with the Siberian hamster extract, and specific IgE-antibodies against Siberian hamster, were strongly positive in all six patients. Determinations of specific IgE-antibodies against C. cricetus and M. auratus were negative in all patients. IgE-immunoblotting of the sera revealed two IgE-binding fractions (MW 18 and 32 kDa) in five of the six sera. Specific bronchial provocation tests resulted in early asthmatic responses in the two patients who were challenged. CONCLUSIONS: The present study reveals the Siberian hamster to be able to induce both sensitization and disease, and this species of hamster should be taken into consideration as a cause of respiratory disease in exposed subjects. A noteworthy finding was the lack of sensitization in our patients to common hamster allergens (M. auratus and C. cricetus) that are usually tested when hamster allergy is suspected.

Relationship between induced sputum cell counts and fluid-phase eosinophil cationic protein and clinical or physiologic profiles in mild asthma.

BACKGROUND: Sputum analysis is the only non-invasive method to examine airway inflammatory processes in subjects with asthma. The aim of this study was to investigate the relationship between cell counts and fluid phase levels in induced sputum in subjects with mild asthma, and the severity of asthma as assessed by clinical, physiologic and blood measurements. METHODS: Forty patients with mild asthma, aged 17 to 49 years were studied (good sputum sample only from 31). On the first day, spirometry and methacholine challenges were performed. After 2 to 4 days, venous blood for absolute eosinophil count and eosinophil cationic protein (ECP) measurement was obtained and sputum was induced by inhalation of hypertonic saline. For the next 15 days subjects recorded their peak expiratory flow (PEF), symptom scores, and beta2-agonist requirements twice daily. Differential counts of leukocytes were done on cytospin preparations of homogenized sputum and the supernatant was examined for eosinophil cationic protein (ECP). RESULTS: Sputum eosinophil counts and not neutrophil, epithelial cells, macrophages, or lymphocytes, were inversely correlated to FEV1/FVC % (r = -.57, P = .0008) and to PC20-methacholine (r = -.40, P = .024). No statistical relationship was obtained between eosinophil counts and either symptom scores, bronchodilator requirements, or daily PEF variability. Sputum ECP values were correlated to FEV1/FVC% (r = -.41, P = .026) but not to PC20 (r = -.32, P = .08) or clinical scores or PEF variation. A trend to significance was appreciated between peripheral blood and sputum eosinophil counts (r = .34, P = .067) and no relationship was found between sputum and serum ECP values (r = .10, P = .38). CONCLUSIONS: Although sputum markers give some information about disordered lung function and physiologic changes in the airways, they are not the only factors concerned in the clinical expression of mild asthma.

Sensitivity and maximal response to methacholine in perennial and seasonal allergic rhinitis.

BACKGROUND: Airway hyperresponsiveness to pharmacological agonists is a common feature in subjects with allergic rhinitis. OBJECTIVE: The aim of this study was to investigate differences in threshold value and shape of the concentration-response curves to methacholine between subjects with perennial allergic rhinitis and subjects with seasonal rhinitis. METHODS: We studied a sample of 72 non-asthmatic patients with allergic rhinitis. They were subdivided into two groups: subjects with only seasonal symptoms and skin sensitization to grass and/or Parietaria pollen allergens (seasonal group, n = 38), and subjects with perennial symptoms and skin sensitization to house dust mite, alone or with other allergens (perennial group, n = 34). They were challenged with methacholine (up to 200 mg/mliter), and concentration-response curves were characterized by the threshold value (PC20 = provocative concentration of methacholine required to produce a 20% fall in FEV1) and maximal response plateau, if possible. The measurements in the seasonal group were done within the pollen season. RESULTS: The geometric mean methacholine PC20 for subjects of the perennial group was 6.9 mg/mliter, compared with 23.4 mg/mliter in subjects of the seasonal group (P < 0.01). A plateau response was detected in 16 subjects of the perennial group and in 28 subjects of the seasonal group (P < 0.05). Moreover, the level of plateau was higher in subjects of the perennial group when compared with subjects of the seasonal group (23.8 +/- 2.0% vs 19.2 +/- 1.6%, P < 0.05). CONCLUSION: In subjects with allergic rhinitis, sensitization to perennial allergens is associated not only with lower methacholine threshold values, but also with lower prevalence and higher level of plateau than sensitization to pollen allergens.

Relationship between airway responsiveness and peak expiratory flow variability in subjects with allergic rhinitis.

BACKGROUND: Previous studies have demonstrated an increase in diurnal variation of peak expiratory flow (PEF) in subjects with allergic rhinitis who had decreased methacholine PC20 values. The relationship between PEF variability and some indices of the concentration-response curve to methacholine such as the position and level of the maximal response-plateau has not been studied. OBJECTIVE: The study was carried out to determine differences in PEF variability between subjects with allergic rhinitis who showed plateaus on the concentration-response curves to methacholine at mild degrees of airway narrowing, and patients in whom no plateau was detected. METHODS: Forty-three nonasthmatic patients with allergic rhinitis were included in the study. Subjects underwent methacholine challenge tests with doubling concentrations from 0.39 to 200 mg/mL and measured their PEF three times daily for the next seven days, using mini-Wright peak flow meters. The concentration-response curves to methacholine were characterized by the threshold value (PC20 = provocative concentration required to produce a 20% fall in FEV1) and, if possible, by the position (EC50 = concentration of methacholine that produced 50% of the maximal response) and maximal response-plateau (FEV1 falls < or = 5% after at least three of the highest concentrations). The variability of PEF was expressed as the amplitude percent mean. RESULTS: No correlations were observed between amplitude percent mean and PC20 (r = -.23, NS), EC50 (r = -.07, NS), or level of plateau (r = .02, NS). The amplitude percent mean was higher in subjects who had decreased methacholine threshold values without plateau (geometric mean = 8.3%; range = 3.8% to 14.2%) than in subjects who had decreased threshold values and plateaus (geometric mean = 4.5%; range = 2.4% to 9.9%; P < .01), or subjects who had normal threshold values and plateaus (geometric mean = 4.4%; range = 1.6% to 10.8%; P < .01). Although subjects who had decreased threshold values and plateaus showed higher methacholine responsiveness than subjects with normal threshold values and plateaus (geometric mean PC20 = 6.2 mg/mL versus 107.1 mg/mL, P < .01; geometric mean EC50 = 3.1 mg/mL versus 9.1 mg/mL, P < .01; mean +/- SEM level of plateau = 17.2 +/- 1.8% versus 28.8 +/- 1.1%, P < .001), the difference in amplitude percent mean was not significant. CONCLUSIONS: The loss of plateau on the concentration-response curves to inhaled methacholine at mild degrees of airway narrowing identifies those subjects with allergic rhinitis who show a greater PEF variability. The PEF variability and airway responsiveness are not interchangeable terms.

[Relations between nonspecific bronchial hyperreactivity, diurnal variation of peak expiratory flow and medication requirements in patients with mild asthma]. / Relación entre hiperrespuesta bronquial inespecífica, variación diaria del flujo espiratorio máximo y necesidades de medicación en pacientes con asma leve.

To assess the relation between non-specific bronchial hyperreactivity, we recorded diurnal peak expiratory flow variation (PFV) and asthma symptoms in 36 individuals with mild allergic asthma. The patients were challenged with methacholine to induce decreases greater than 40% in FEV1, or until a maximum of 200 mg/ml had been administered. Over the next 14 days, PFV was measured three times per day and symptoms and inhaled salbutamol requirements were recorded. In the 11 patients with complete dose-response curves, the geometric mean of diurnal PFV variation (% mean range) was 5.0%; this parameter was 8.3% (p < 0.01) in the 25 subjects whose curves did not reach a plateau. A correlation (r = -0.56, p < 0.001) was found between PC20 and % mean range. PFV for the sample as a whole. In the 11 patients with complete curves, however, no correlation (r = -0.31, p = NS) between % mean range of PFV and PC20 was found. Nor could the plateau (r = 0.19, p = NS) or EC50 (r = -0.26, p = NS) be found for these patients. The geometric mean for PC20 in the 12 subjects who needed salbutamol throughout the 14-day study period after methacholine challenge was 1.06 mg/ml; this parameter was 1.32 mg/ml (p = NS) for those with no symptoms. A plateau was reached by 2 of the 12 patients who experienced asthma symptoms and in 9 of the 24 who were asymptomatic (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inhaled budesonide on seasonal changes in sensitivity and maximal response to methacholine in pollen-sensitive asthmatic subjects.

The aim of this study was to investigate the effect of inhaled budesonide on modifications of the provocative concentration of agonist causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) and maximal response plateau to inhaled methacholine during the pollen season in pollen-sensitive subjects with mild asthma. The effects of inhaled budesonide (800 micrograms.day-1) on the threshold value (PC20) and maximal response plateau to inhaled methacholine were studied in 28 pollen-sensitive subjects with mild asthma during a pollen season in a randomized, double-blind, placebo-controlled parallel fashion. They were challenged with methacholine (up to 200 mg.ml-1) in February (preseasonal assessment) and during the middle of the pollen season (in May and again in June). Subjects treated with budesonide (n = 13) were protected from the decrease in PC20 seen in the placebo (n = 15) group (geometric mean PC20 placebo group: preseasonal = 8.51, May = 2.19 and June = 1.78 mg.ml-1; budesonide group: preseasonal = 3.71, May = 3.23 and June = 2.40 mg.ml-1; intergroup differences in doubling concentrations, p < 0.05). Among 10 subjects in the placebo group who reached plateau during the preseasonal assessment, seven lost the plateau in May and six in June. In the budesonide group, among seven subjects who reached plateau during the preseasonal assessment, three lost the plateau in May and four in June. Between-group differences were not significant. We conclude that in pollen-sensitive subjects with mild asthma, inhaled budesonide blocks the effects of natural allergen exposure on the methacholine threshold value.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of concentration-response curves to inhaled methacholine after the pollen season in subjects with pollen induced rhinitis.

BACKGROUND: The effect of cessation of exposure to pollen on the concentration-response curves to inhaled methacholine was investigated. METHODS: Methacholine inhalation challenges (up to 200 mg/ml) were performed in 13 non-asthmatic patients with grass and/or Parietaria pollen-induced rhinitis during the pollen season, and one and four months after it. Concentration-response curves were characterised by their PC20, position, and plateau. RESULTS: Geometric mean methacholine PC20 increased from 6.4 mg/ml during the pollen season to 28.2 mg/ml and 54.9 mg/ml one and four months after the end of season, respectively. The mean (SE) level of the plateau decreased from 30.5 (4.3%) in the pollen season to 23.3 (3.7)% and 20.1 (3.3)% one and four months after the end of pollen season, respectively. Although the methacholine concentration that produced 50% of the maximal response increased from 2.9 mg/ml to 4.3 mg/ml and 6.0 mg/ml, the differences were not significant. CONCLUSIONS: In non-asthmatic patients with pollen-induced rhinitis cessation of exposure to pollen is associated with significant modifications in the methacholine threshold value and level of plateau, and with a small shift in the concentration-response curves to the right.

Airway responsiveness to methacholine and risk of asthma in patients with allergic rhinitis.

To find out whether airway hyperresponsiveness is associated with a greater risk of asthma in subjects with allergic rhinitis, 66 nonasthmatic patients with allergic rhinitis underwent inhalation challenge with methacholine. Each patient was reevaluated prospectively at least once each year and a diagnosis of asthma was accepted if the subject developed episodic wheezing and/or cough plus airway obstruction and at least a 15% increase in FEV1 after inhaled salbutamol. Those subjects who developed asthma and ten individuals who did not develop asthma were rechallenged after the first asthma symptoms or at the end of the followup period, respectively. Risk of developing asthma during the followup period (mean of 43.8 months, range 36 to 70) was similar (P > .05) in those individuals who previously had airway hyperresponsiveness (2 of the 19 patients), when compared with subjects who were previously nonresponders (4 of the 47 patients). Further, in those subjects who developed asthma, geometric mean (range) PC20 decreased from 11.75 (0.40 to 50) during the initial evaluation to 1.66 (0.15 to 11.07) mg/mL after the first asthma symptoms (P < .05). No significant modifications of PC20 were detected in subjects who did not develop asthma. We conclude that a single determination of methacholine PC20 is not a reliable marker of the subsequent development of asthma in patients with allergic rhinitis.

Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients.

We examined the effect of cessation of exposure to pollen on non-specific airway responsiveness in 10 grass and/or parietaria pollen sensitive asthmatics. Three methacholine inhalation challenges were performed, the first during pollen season (seasonal period), the second 2 months after the end of season (short time after seasonal period), and the third 5 months after the end of season (long time after seasonal period). The dose-response curves to methacholine were characterized by the PC20 (provocative concentration of methacholine required to produce a 20% fall in FEV1) and maximal response plateau, if possible. A maximal response plateau on the dose-response curve was considered to be present if three or more data points for FEV1 fell within a 5% response range. The challenge was stopped when FEV1 dropped more than 50% or the highest concentration of methacholine (200 mg/ml) was reached. The geometric mean (range) methacholine PC20 increased from 1.08 (0.18-37.22) in the seasonal period to 4.67 (0.71-200) mg/ml during the long time after seasonal period (P < 0.01). On the other hand, in six subjects in whom it was possible to obtain a plateau on at least one challenge, the level of the maximal response decreased from (mean +/- s.e.m.) 44.1 +/- 4.9 in the seasonal period to 30 +/- 4.4 during the long time after seasonal period (P < 0.05). These results suggest that in pollen sensitive asthmatic patients, the cessation of exposure to pollen is associated with a reduction of non-specific bronchial responsiveness (PC20 and maximal degree of airway narrowing to methacholine).

Lung function and bronchial response to methacholine in young adults who had asthma in childhood.

Lung function and bronchial response to methacholine were studied in 47 young adults who had had childhood asthma, and after a period of 14-21 years, showed a different clinical evolution. At present, these subjects have been classified in four clinical groups: asymptomatic, rhinitic, asthmatic only due to exercise, and asthmatic. The same study was performed in 23 healthy individuals without personal histories of respiratory or allergic pathology. We found low spirometric basal values in both the asthmatic group (FEV1 and FEF25-75) and in the group with asthmatic responses to exercise (FEF25-75). No significant differences were found among asymptomatic, rhinitic, and control groups. While airway hyperreactivity was observed in patients who still had asthma, the bronchial response to methacholine in asymptomatic and rhinitic groups was not different from the control group. We conclude that both lung function and bronchial response to methacholine in most of the adults who had asthma in infancy and had been without asthmatic symptoms for many years are similar to those observed in the general population.