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Baker's asthma. Clinical and immunological studies.

Seven bakers with respiratory symptoms were evaluated by skin tests, RAST assay for specific IgE antibodies to rye and wheat, inhalation challenge with methacholine for the determination of non-specific bronchial reactivity, and bronchoprovocation with rye and wheat extracts for the determination of antigen-specific bronchial reactivity. An immediate asthmatic response to antigen challenge was observed in four subjects and all of them had a high level of flour-specific IgE antibodies. The serum RAST values provided a more accurate predictive value than the degree of cutaneous sensitivity determined by skin testing with respect to the bronchial response to antigenic challenge. Among those who reacted positively to antigenic bronchoprovocation, a much lower antigen dose was required to elicit a positive reaction if the subject also had an increased degree of non-specific bronchial reactivity. An elevated RAST value was not found in thirty-eight asymptomatic bakers or in ten asthmatics who had no occupational exposure to flour. Thus, baker's asthma appears to be a form of allergic asthma to cereal flours mediated by specific IgE antibodies. Both the level of serum IgE antibodies and the degree of non-specific bronchial reactivity are important factors which may influence a baker's bronchial response upon inhalation of cereal flours.

Adult↗

Sodium cromoglycate in histamine and methacholine reactivity in asthma.

The effect of increasing concentrations of inhaled sodium cromoglycate (SCG) (2, 10, 20 and 40 g/l) on histamine and methacholine bronchial reactivity was studied in nine patients with extrinsic bronchial asthma. The responses to histamine and methacholine were expressed in terms of provocative concentrations producing 20% fall in the FEV1 (PC20). The PC20 for histamine and methacholine was unaffected by all the concentrations of SCG used in the study. These results suggest that the effect of SCG on the bronchial smooth muscle or on the muscarinic receptors is minimal.

Adolescent↗

Bronchial responsiveness to methacholine during airway cooling in normal subjects.

In order to investigate the effects of airway cooling on bronchial responsiveness in normal subjects, we measured bronchial responsiveness to inhaled methacholine with and without the inhalation of cold air. Two out of seven subjects showed an increase in baseline respiratory resistance (Rrs) during cooling of the airway but the other five subjects showed little change in their baseline Rrs. All subjects increased bronchial responsiveness to methacholine. Additionally, the threshold dose of methacholine decreased to one-third of the control dose with cooling of the airway. We speculate that airway cooling increased bronchial responsiveness to methacholine in normal subjects presumably due to increased vagal tone, increased alpha-adrenergic activity and/or a release of chemical mediators.

Adult↗

Associations between asthma history, atopy, and non-specific bronchial responsiveness in young adults.

In 105 subjects taken from a student population and aged between 15 and 30 there was a strong positive association between the presence of the atopic state, defined by skin tests, and a high level of non-specific bronchial responsiveness to methacholine (chi 2 = 10.5, d.f. = 2, P = 0.01). Regression analysis showed a history of asthma, and the symptom of wheeze, to be predominantly predicted by the degree of bronchial responsiveness (R2 = 31%), with only a minor independent contribution from the degree of atopy (R2 a further 5%). The genetic or other reasons for the association between bronchial responsiveness and atopy may have importance in understanding the aetiology of allergic asthma.

Adolescent↗

Histamine and methacholine do not increase nasal reactivity.

Allergen provocation in the nose increases the non-specific nasal reactivity. The aim of this trial was to determine whether this 'priming effect' can be caused by histamine or methacholine, which is the most important biochemical mediator of allergic rhinitis, and an analogue to the important neurotransmittor, acetylcholine, respectively. Intranasal provocation tests with the two substances were carried out on thirteen normal subjects, and repeated 1 hr and 1 day later. The response, measured as the number of sneezes, the amount of blown secretion and the increase in nasal airway resistance, did not change with consecutive provocations. It was concluded that neither histamine nor methacholine were responsible for the allergen-induced 'priming' of the nasal mucous membrane.

Administration, Intranasal↗

Pattern of specific airway response in asthma due to western red cedar (Thuja plicata): relationship with length of exposure and lung function measurements.

In order to investigate the relationship between the pattern of response (immediate, late and dual) to specific bronchial challenge test with plicatic acid or red cedar extract and the clinical features of asthma, 332 patients with asthma induced by western red cedar dust were examined at the time of diagnosis. Specific challenge test induced in thirty-one patients (9.3%) an isolated immediate reaction, in 144 patients (43.4%) an isolated late reaction and in 157 patients (47.3%) a dual reaction. Patients with a dual reaction had a longer period of exposure to red cedar dust between the onset of the respiratory symptoms and the time of the definitive diagnosis, a lower FEF 25-75% and a greater degree of non-specific bronchial hyperresponsiveness compared to patients with isolated immediate or isolated late reactions; the difference in bronchial hyperresponsiveness to methacholine among the three groups persisted when the values were adjusted for the different baseline value of FEV1. There was no difference in the prevalence of specific serum IgE antibodies to plicatic acid-human serum albumin conjugate among the three groups of patients with different type of response to red cedar. Except for the greater degree of non-specific bronchial hyperresponsiveness, patients with isolated late reactions were not different from those with isolated immediate reactions in other clinical findings. These findings indicate that a dual reaction in patients with occupational asthma due to simple chemical agents is indicative of a greater severity of disease at diagnosis. The pathogenetic mechanism of various types of asthmatic reaction is unknown and it is likely to be different between isolated immediate and isolated late reactions.

Adult↗

Comparison of nasal responsiveness to histamine, methacholine and phentolamine in allergic rhinitis patients and controls.

In a selected group of rhinitis patients with an IgE-mediated allergy to house dust mites the nasal response to insufflation of histamine chloride, methacholine and phentolamine was demonstrated to be higher than in a control group. With the methods used histamine chloride was better at discriminating between healthy subjects and patients than methacholine or phentolamine. This discrimination was shown by assessing the severity of reflex-mediated symptoms such as the number of sneezes and the amount of secretion, and not by differences in nasal airway resistance.

Adult↗

Effect of nedocromil sodium on adenosine- and methacholine-induced bronchospasm in asthma.

The effect of nedocromil sodium on adenosine-induced bronchospasm was investigated in eight asthmatic patients. Nedocromil sodium (4 mg) administered by aerosol 10 min before challenge, effectively inhibited adenosine-induced bronchospasm. In another group of six asthmatic patients, nedocromil sodium administered in the same way did not reduce the bronchial response to methacholine. These results support the view that adenosine-induced bronchospasm may be prevented by a membrane stabilizing drug and is not mediated through cholinergic pathways. The mechanism(s) by which nedocromil sodium inhibits adenosine-induced bronchospasm requires further investigations.

Adenosine↗

Comparison of cellular and protein changes in bronchial lavage fluid of symptomatic and asymptomatic patients with red cedar asthma on follow-up examination.

Seventeen patients with occupational asthma due to western red cedar had bronchial lavage during follow-up examination after removal from exposure for at least 1 year. Seven patients were asymptomatic while ten continued to have symptoms of asthma requiring treatment. Symptomatic patients had evidence of airway inflammation, as reflected by a significantly higher total cell count, neutrophils and eosinophils, as well as an increase in protein and albumin in their bronchial lavage fluid compared to those without symptoms. Asymptomatic patients had no evidence of airway inflammation in the lavage fluid. There was no correlation between the degree of non-specific bronchial hyperresponsiveness and the number or percentage of inflammatory cells to suggest that cellular infiltration is the sole cause of persistent bronchial hyperresponsiveness.

Adult↗

Lymphocyte subsets in bronchoalveolar lavage fluid obtained from stable asthmatics, and their correlations with bronchial responsiveness.

Bronchial responsiveness to methacholine (PD20 FEV1) was assessed in 22 asthmatic subjects approximately 5 days prior to bronchoalveolar lavage (BAL). A PD20 FEV1 could not be attained in 20 matched controls with normal pulmonary function. BAL was performed in all subjects, 3 x 60 ml aliquots of buffered saline being introduced into a segment of the middle lobe and immediately aspirated into siliconized glassware at 4 degrees C. After filtration, cells were counted, and the cell pellet resuspended in medium 199. Cytospin slides were prepared and a differential cell count performed. Lymphocyte subsets were identified by labelling further cytospin preparations with specific monoclonal antibodies (Leu series) against T3, T4, T8 and B cell markers, followed by a fluorescent antibody marker. The slides were coded, and 100 lymphocytes were then randomly scanned for fluorescence on each cytospin preparation. The median total lymphocyte counts were significantly greater in the asthmatic subjects, but this increase was confined to the T cell subgroups. The mean T4/T8 ratio was similar in asthmatic (1.51) and control (1.45) subjects. Log PD20 FEV1 correlated positively with total lymphocyte counts (r = 0.42, P less than 0.05), and with total T8 counts (r = 0.60, P less than 0.05). Correlations between bronchial responsiveness and T3, T4 and B lymphocyte numbers all failed to reach significance, and there was no correlation with T4/T8 ratios. The increase in BAL lymphocyte counts in asthma appears to be due to an absolute increase in T cell subsets, especially the T8 lymphocyte subgroup, and is most marked in mild asthmatics.

Adolescent↗

Ketotifen does not inhibit asthmatic reactions induced by toluene di-isocyanate in sensitized subjects.

In order to determine whether treatment with ketotifen inhibits asthmatic reactions induced by toluene di-isocyanate (TDI), we studied six sensitized subjects with previously demonstrated dual or late asthmatic reaction after inhalation challenge with TDI. Ketotifen (1 mg b.i.d., orally) or placebo was administered for 7 days to the examined subjects, according to a double-blind, cross-over, placebo-controlled study design. When the subjects were treated with either ketotifen or placebo, FEV1 markedly decreased after exposure to TDI. These results suggest that the anti-asthmatic agent ketotifen is not effective in TDI-induced asthma and suggest that it should not be used in the prophylaxis of asthmatic reactions induced by TDI in sensitized subjects.

Asthma↗

Nedocromil sodium is more potent than sodium cromoglycate against AMP-induced bronchoconstriction in atopic asthmatic subjects.

Nedocromil sodium is a new chemical entity which shows similar properties to sodium cromoglycate (SCG) and in addition exhibits a preferential activity in stabilizing mucosal mast cells. We have compared the effect of inhalation of nebulized placebo, SCG and nedocromil sodium on the bronchoconstrictor response to inhaled adenosine monophosphate (AMP) in eight atopic asthmatic subjects aged 25 yr (range 21-32 yr). The geometric mean provocation doses of AMP required to produce a 20% decrease in FEV1 (PD20FEV1) and a 40% decrease in Vmax30 (PD40 Vmax30) following placebo were 4.9 (0.3-14.2) and 1.8 (0.1-8.4) mumol respectively. Prior inhalation of both SCG and nedocromil sodium significantly inhibited the bronchoconstrictor response to AMP with PD20FEV1s of 36.6 (4.0-132.7) and 134 (12.4-560), and PD40 Vmax30 values of 20.5 (1.4-110) and 101.6 (5-560) mumol respectively (P less than 0.001). Nedocromil sodium was 3.9 (FEV1) and 8.0 (Vmax30) times more potent than SCG (P less than 0.001). In conclusion, both drugs inhibit the bronchoconstrictor response to inhaled AMP, and nedocromil is at least 4-8 times more potent than SCG.

Adenosine Monophosphate↗

The relationship between atopy and non-specific bronchial responsiveness.

Atopy is often regarded as a risk factor for the development of asthma, particularly childhood asthma and occupational asthma. This could reflect an association with non-specific bronchial responsiveness (NSBR), though atopy could influence asthma independently. We have evaluated the possible relationship between atopy and NSBR (PD20FEV1 to methacholine) in the siblings of 59 probands with atopic asthma. Thirty-four (58%) were atopic (greater than or equal to 1 prick test with weal diameter greater than or equal to that of a 0.1% histamine control) and 28 (47%) showed NSBR. Atopy and NSBR occurred together more frequently than would be expected by chance (P less than 0.05); both variables being observed in 20 subjects, neither in 17, and only one in 22. A significant association was also noted when atopy was defined by a serum total IgE greater than 150 IU (or greater than 50 IU), but when atopy was defined by other commonly used criteria (greater than or equal to 2 prick tests with weal diameter greater than or equal to histamine control; or weal diameter 2 mm or more greater than a saline control), no significant association was demonstrated. Furthermore, linear logistic regression and multiple regression analyses showed that both the presence and the degree of NSBR were influenced much more by the baseline level of FEV1 than by atopic status. At best, atopy accounted for 10% of the variance of the PD20 measurements. We conclude that atopy is associated with NSBR but not strongly; that the relationship may be readily obscured according to the defining criteria used for atopy; and that atopy should not be used as a marker for NSBR.

Adolescent↗

Venous blood platelets decrease during allergen-induced asthmatic reactions.

To determine whether circulating platelets alter during asthmatic reactions induced by allergens, we studied nine subjects previously shown to develop an early or dual asthmatic reaction after inhalation challenge with extracts of house dust mite or grass pollen. In each subject, FEV1, circulating platelets and leucocytes were measured before, 15, 30 and 60 min, and 2, 4, 6 and 8 hr after inhalation of allergen and diluent control administered in a single-blind, randomized fashion. The same procedure was repeated in six of the nine subjects after bronchoconstriction induced by methacholine. Each subject developed an early asthmatic reaction after allergen inhalation challenge, which was followed by a late asthmatic reaction in six subjects and by an equivocal late asthmatic reaction in two of them (fall in FEV1 of 15 and 17% respectively). Compared with the control day, circulating platelets significantly decreased during the allergen-induced early asthmatic reaction (P less than 0.025, at 30 min). Platelet counts returned to baseline values within 4 hr and remained steady thereafter both in subjects who did and did not develop a late asthmatic reaction. No changes in platelet counts occurred after bronchoconstriction induced by methacholine. Diurnal increase of leucocyte numbers occurred after challenge with both allergen and diluent control. These results suggest that platelets may be involved in the pathogenesis of allergen-induced asthmatic reactions.

Adolescent↗