The study of bronchial hyperresponsiveness in asthmatic children by forced oscillation technique.

We have studied the bronchial hyperresponsiveness (BHR) of children with normal controls and asthma by methacholine inhalation challenge, using a forced oscillation method. Four parameters, respiratory conductance (Grs), bronchial responsiveness (PD35Grs), bronchial sensitivity (Dmin) and reactivity (SGrs) were studied. There were three patterns of dose-response curves identified in this study, which were significantly correlated to the clinical severity of asthma. (r = 0.846, p less than 0.001, Spearman's rank correlation). There were significant negative correlations between control Rrs (Rrs cont.) and age (r = 0.514, p less than 0.001) or body height (r = 0.685, p less than 0.001). Positive correlations between SGrs and subjects' age (r = 0.457, p less than 0.001) and body height (r = 0.496, p less than 0.001) were also noted. In the normal controls, Dmin and PD35Grs were over 25 units and 50 units, respectively. The Grs for normal children was statistically higher than that of asthmatic children (p less than 0.05). In the asthmatic children, there were significant differences among all subgroups in PD35Grs (p less than 0.001) and Dmin (p less than 0.01). In summary, the bronchial provocation test using the forced oscillation technique is simple, fast and easy to be applied to children. In addition to being capable of investigating BHR, it may offer valuable information for the clinical diagnosis and treatment of asthmatic children.     

The effects of inhaled leukotriene E4 on the airway responsiveness to histamine in subjects with asthma and normal subjects

Eight subjects with asthma inhaled on separate occasions leukotriene E4 (LTE4) (6.1 nmol, geometric mean), methacholine, and diluent, which produced an average 41.0%, 37.0%, and 3.3% decrease in specific airway conductance (SGaw), respectively. When the SGaw had recovered to baseline levels at 60 minutes after challenge, the provocative dose of inhaled histamine that produced a 35% decrease in SGaw (PD35) was determined. The histamine PD35 observed after inhalation of LTE4 was 0.46 mumol, and this was significantly less than the histamine PD35 observed after inhalation of methacholine (0.88 mumol; p less than 10(-4) and diluent (0.97 mumol; p less than 10(-5). Histamine responsiveness was also enhanced by a fiftyfold lower dose of LTE4 (p = 0.005), and the enhancement was less than that elicited by the higher dose of LTE4 in the same individuals (p = 0.02). The changes in histamine PD35 during a 1-week period after LTE4 and methacholine challenges were compared in four subjects with asthma. There was a time-dependent enhancement in histamine responsiveness that reached a maximal of 3.5-fold at 7 hours after LTE4. The enhancement had disappeared by 1 week. Similar changes were not observed after methacholine challenge, which elicited the same degree of bronchoconstriction as LTE4. Inhalation of LTE4 in five normal subjects that produced a mean 37.6% decrease in SGaw did not change histamine responsiveness for up to 7 hours. These findings suggest that LTE4 may play a role in the perpetuation of nonspecific airway hyperresponsiveness in bronchial asthma.     

Effective site of bronchodilation by antiasthma drugs in subjects with asthma

We studied the effective sites of airway response to atropine and fenoterol aerosols and to the intravenous injection of aminophylline in patients with stable and spontaneous asthma, by the simultaneous assessment of respiratory resistance (Rrs) and anatomic dead space (VD). Central airway response was determined by VD, and overall response was determined by Rrs. Peripheral airway response was inferred from Rrs when the change in VD was slight. Atropine (4 mg/ml) or fenoterol (0.4 mg/ml) was continuously inhaled during tidal breathing for 5 minutes. Inhalation of both atropine and fenoterol increased Grs (reciprocal of Rrs) (p less than 0.01) with a simultaneous increase in VD (p less than 0.01) in the patients with stable and spontaneous asthma. Fenoterol increased Grs more than did atropine at an equivalent increase in VD in patients with spontaneous asthma (p less than 0.05). Intravenous injection of aminophylline (250 mg) had no effect on either Grs or VD in patients with stable asthma, but it significantly increased Grs (p less than 0.01) without change in VD in patients with spontaneous asthma. These results suggest that the predominant sites of bronchodilation induced by inhaled atropine are the central airways, that those sites induced by intravenous injection of aminophylline are the peripheral airways, and that inhaled fenoterol dilates both the central and peripheral airways in subjects with asthma. Differences among clinically used bronchodilators on the effective sites may be considered in the treatment of bronchial asthma.     

Measurement of bronchial hyperreactivity in infants and preschool children using a new method

We report a new method for examination of bronchial reactivity by measuring transcutaneous oxygen pressure (tcPO2) during the inhalation of histamine in stepwise incremental concentrations. The correlation between changes in tcPO2 and those in PEFR or FEV1 was high (P less than .001). When the fall in PEFR or FEV1 was more than 20% compared with baseline, the fall in tcPO2 was more than 10%. We also measured the dose of radiolabeled aerosol (99mTc-DTPA) inhaled into the lung using a scintillation camera. When aerosol is inhaled during tidal breathing, there are adequate correlations between the dose of aerosol in the lung and both the age and height of the patients (P less than .001). When aerosol was inhaled during crying, little deposit within the lung was shown. When the inhalation challenge test was done during a sleeping period for children aged under 2 years, the loading dose of aerosol in the lung was sufficient. The geometrical means of respiratory threshold of histamine (RT-Hist) among 106 asthmatic and 11 control children, aged 2 to 6 years, were 1182 and 4414 micrograms/mL, respectively. The means of RT-Hist in 17 children with bronchial asthma, nine with atopic dermatitis, five with respiratory disease, and nine controls, aged under 2 years, were 1152, 964, 544, and 3402 micrograms/mL, respectively.     

Studies of adenosine inhalation in asthmatic patients

In order to determine the mechanism of bronchoconstriction induced by the inhalation of adenosine in asthmatics, we measured, by the astograph method, cyclic nucleotides, leukotrienes and thromboxane B2 before and after the inhalation, and we studied the relationship between serum theophylline concentration and Rrs cont, Dmin and S Grs/Grs cont of the astogram obtained by inhaled adenosine. Plasma TXB2 level was significantly raised (p less than 0.05) after inhalation, but cAMP, cGMP, LTB4 and LTC4 did not change. In the astogram, Dmin was significantly elevated (p less than 0.01) when plasma theophylline concentration was raised to the therapeutic level, but Rrs cont and S Grs/Grs cont showed no remarkable change. We confirmed that inhaled adenosine caused bronchoconstriction in asthmatic patients, and that Dmin was elevated after the administration of theophylline. These results suggest that TXB2, a metabolic product of arachidonic acid, may be one of the most important mediators in the bronchoconstriction mechanism of inhaled adenosine.     

Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?

To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.     

Inhalation provocation test with house dust allergen using tidal breathing

Using the modified 3-Hz oscillation method, the inhalation challenge test was performed with house dust allergen upon subjects while tidal breathing throughout the test. Their total respiratory resistance (Rrs) was continuously monitored with the inhalation of saline as a control, and 250-, 50-, and 10-fold diluted allergen solution to the inhalation of aerosolized metaproterenol. The starting point of the induced bronchoconstriction was checked and as soon as Rrs increased up to twice the base-line value, the subjects inhaled the aerosolized metaproterenol. From the dose-response curve of Rrs, the dose of inhaled allergen (minimum dose) as bronchial sensitivity was determined; also the decreasing rate of respiratory conductance, which was calculated from the slope of elevation of Rrs, as bronchial reactivity. It was found that the more diluted allergen required for a positive skin reaction, the more likely the patients were to have a subsequent positive bronchial inhalation challenge to house dust allergen. There was a relationship between the increased bronchial reactivity and the increased RAST score. These results indicate that this inhalation challenge test is specific, safe, and time-saving.     

Effects of ultrasonically nebulized distilled water on respiratory resistance and breathing pattern in normals and asthmatics

The purpose of this study was to analyze changes in respiratory resistance (Rrs) and breathing pattern in normal and asthmatic subjects after exposure to ultrasonically nebulized distilled water (UNDW). After measurement of baseline Rrs and breathing pattern, ten normals inhaled UNDW for 30, 60, 120, 240 and 480 s administered at 15 min intervals. After the 480 s exposure, subjects inhaled two puffs of metaproterenol. Rrs was measured immediately before and after each exposure to UNDW and after metaproterenol while breathing pattern was continuously monitored. Ten asthmatics were exposed to UNDW and metaproterenol in a similar time sequence, but the durations of exposure to UNDW were 15, 30, 60, 120 and 240 s. Mean (+/- SD) and frequency histograms of minute ventilation (VE), tidal volume (VT), frequency, inspiratory time, fractional inspiratory time, mean inspiratory flow (VT/TI) and end-expiratory level at baseline were compared to values after each exposure to UNDW and after metaproterenol. All subjects experienced laryngeal irritation or cough during the exposure. In normals, there were no changes in Rrs or any of the components of breathing pattern. In asthmatics, 15 and 30 s exposures produced no changes in Rrs or breathing pattern. With subsequent longer exposures, mean Rrs showed a stepwise significant increase, along with parallel increases of VT/TI and end-expiratory level. VE increased after 60 and 120 s exposure, but reached a plateau after 240 s exposure despite continued increase in Rrs.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Standardization of inhalation provocation tests: Influence of nebulizer output,particle size,and method of inhalation

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 μm aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 μm AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV₁) by 20% (PC₂₀). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC₂₀. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.     

The effect of nedocromil sodium on the bronchoconstrictor effect of neurokinin A in subjects with asthma

We have previously demonstrated that the neuropeptide, neurokinin A (NKA) (substance K), causes bronchoconstriction in subjects with asthma. In a double-blind, crossover study we investigated the effect of nedocromil sodium on NKA-induced bronchoconstriction in subjects with asthma. Twelve patients with mild asthma (mean FEV1 percent predicted +/- SE, 87.3 +/- 3.4) inhaled on 2 separate days either nedocromil sodium, 4 mg, or placebo, as two puffs from a metered-dose aerosol, 30 minutes before challenge with NKA. NKA was inhaled at three concentrations (10(-7), 3.10(-7), and 10(-6) mol/ml). The specific airway conductance (SGaw) and FEV1 were measured before and 5 and 15 minutes after each concentration step. On the placebo-treatment day, NKA caused a concentration-dependent decrease in SGaw and FEV1 (mean log for the provocative concentration of NKA causing a 35% fall in SGaw [10(-7) mol/ml], 0.49; mean log for the provocative concentration of NKA causing a 15% fall in SGaw [10(-7) mol/ml], 0.90). The inhalation of 4 mg of nedocromil sodium reduced the decrease in both SGaw and FEV1. The maximal percentage decrease in SGaw on the nedocromil sodium-treatment day was 27 +/- 5.2 (versus placebo, 53.3 +/- 5.4; p less than 0.05), and the maximal percentage decrease in FEV1 was 5.5 +/- 1.4 (versus placebo, 12.4 +/- 2.3; p less than 0.05). The dose-response curves for NKA after nedocromil sodium treatment were significantly shifted to the right compared to the curve after placebo-treatment. We conclude that nedocromil sodium protects against NKA-induced bronchoconstriction in subjects with asthma.     

Bronchial allergen challenge: comparison between two different methods of provocation

Bronchial allergen challenge was performed twice in ten well-defined stable asthmatic patients. On each provocation day the allergen was administered either by a standard method at tidal volume breathing or by a dosimeter method. Ten-fold increasing concentrations of allergen were administered with an interval of 10 min. Total amount of allergen of 9, 90, 900, 9000 and 90000 SQ units using the standard method, whereas the corresponding amount by the dosimeter method was 0.5, 5, 50, 500, and 5000 SQ units. The bronchial response was determined by forced expiratory volume in the first second (FEV₁) and by total resistance to breathing (R_t) measured by an opening interrupter method. The provocation was stopped when a decrease of at least 20% of the post-saline FEV₁ and a 4O% increase in post-saline R_t, was observed. A PC₂₀-FEV₁ and a PC₄₀-R_t was calculated by interpolation on the log dose-response curve. The late reaction was recorded and defined as a 20% reduction in peak expiratory flow (PEF) occurring during the 24-hr period after challenge. The comparability of PC₂₀-FEV₁ and PC₄₀-R_t obtained with the standard method and with the dosimeter was high. r= 0.89 and r= 0.88. Furthermore, no significant difference was found by comparing Δ FEV₁ and Δ R_t during provocation by either method as well as the occurrence and magnitude of the late reaction. We conclude that there exists a high comparability of the bronchial response to an allergen challenge performed either by a standard method at tidal volume breathing by continuous inhalation of the allergen aerosol or by a dosimeter method of inhalation despite the difference in the total allergen doses inhaled.     

Seasonal variation of airway function in allergic rhinitis

We set out to examine seasonal variation in airway bronchoconstriction in patients with seasonal allergic rhinitis. Airway conductance and response to methacholine challenge were measured during pollen season, as well as in winter when pollen exposure was not present. Airway conductance and spirometry were performed on 17 subjects during allergy season and in winter. In eight of these subjects the measurements were repeated in the successive allergy season. Methacholine bronchoprovocation was performed on 17 of the subjects in winter and in eight subjects in allergy season. We found airway constriction in both allergy seasons as evidenced by specific airway conductance (SGaw) of 0.188 +/- 0.06 and 0.203 +/- 0.03. In contrast, SGaw during winter was 0.27 +/- 0.11. When winter and summer seasons were compared, both summer SGaw values were significantly lower than winter SGaw, p less than 0.01 and p less than 0.05, respectively. Mean airway sensitivity to methacholine during allergy season was 16.1 breath units and not different than out of season 11.7 breath units; p = NS. The reactivity to methacholine (slope of the dose-response curve) and spirometry (FVC, FEV1, FEV1/FVC) in and out of allergy season were likewise not different. The data indicate that patients with allergic rhinitis have unique physiologic behavior separating them from patients with asthma or normal subjects. They develop seasonal bronchoconstriction unassociated with clinical bronchospasm, but this seasonal bronchoconstriction does not potentiate their sensitivity to methacholine. However, they have increased airway sensitivity to methacholine, and this feature distinguishes them from normal subjects.     

The protective effect of low-dose inhaled fenoterol against methacholine and exercise-induced bronchoconstriction in asthma: a dose-response study.

We compared in a randomized, double-blind study the protective effect of low doses of fenoterol on the airway response to exercise during cold air breathing and an inhalation challenge with methacholine. In six asymptomatic asthmatic persons (mean age, 20.3 years) exercise and methacholine challenges were performed under control conditions and 15 minutes after the inhalation from a metered-dose inhaler of either placebo or 30, 50, 100, and 200 micrograms fenoterol, resulting in 12 separate study sessions within a 3-week period. Airway response was determined by measuring specific airway resistance (sRaw). Exercise tests were standardized by maintaining a constant respiratory heat exchange, with an average (range) of 1.28 (1.15 to 1.45) kcal/min. Methacholine was inhaled at increasing doses until sRaw had doubled (PD100sRaw). Mean postexertional increase of sRaw (SD) after control conditions, placebo, and 30, 50, 100, and 200 micrograms fenoterol aerosol was 27.8 (6.9), 28.9 (10.0), 7.20 (2.7), 9.33 (3.8), 5.57 (2.3), and 5.28 (1.6) cm H2O.s. Fenoterol aerosol was equally effective at all doses administered, whereas methacholine-induced bronchoconstriction was attenuated in a dose-dependent manner. From these observations we suggest that low-dose fenoterol protects against bronchoconstriction induced by exercise, a naturally occurring stimulus reflecting airway hyperresponsiveness.     

Effect of challenge method on sensitivity, reactivity, and maximal response to methacholine.

BACKGROUND: Recent data suggest that the tidal breathing method may produce methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) values significantly lower than the dosimeter method; however, the effect of the challenge method on the shape of the concentration-response curve has not been investigated. OBJECTIVE: To determine the effect of the challenge method on sensitivity, reactivity, and maximal response to methacholine. METHODS: We measured airway responsiveness to methacholine using dosimeter and tidal breathing methods in 30 individuals with suspected asthma. Concentration-response curves were characterized by their PC20 (sensitivity), slope (reactivity), and, if possible, level of plateau. RESULTS: Dosimeter PC20 values were significantly higher than tidal breathing values (geometric mean, 8.9 and 5.2 mg/mL, respectively); the mean difference in PC20 values obtained using each method was 0.78 doubling concentrations (P = .01). The mean slopes were 22.7%/log mg/mL using the tidal breathing method and 24.9%/log mg/mL using the dosimeter method; the mean difference in the slopes obtained using each method was -2.17%/log mg/mL (P = .18). In 10 individuals who showed a plateau with the 2 methacholine challenge tests, the mean level of plateau was 19.8% using the tidal breathing method and 19.5% using the dosimeter method; the mean difference in the plateau values obtained with each method was 0.3% (P = .87). CONCLUSIONS: Although the tidal breathing method produces methacholine PC20 values significantly lower than the dosimeter method, both methods provide similar values for slope and level of plateau. These results suggest that the technical factors that affect methacholine sensitivity and the shape of the curve are different.     

The effect of inspiratory flow rate regulation on nebulizer output and on human airway response to methacholine aerosol

Increased inspiratory flow rate has been demonstrated to decrease pulmonary deposition of inhaled aerosols. To study the effect of inspiratory flow rate regulation on the physiologic response to an active substance administered by aerosol, we compared the effect of high unregulated flow rate (66 to 212 L/min) with regulated low flow rate (20 to 35 L/min) on nebulizer output and on the pulmonary response to methacholine in patients with asthma. Four No. 646 DeVilbiss nebulizers were used in sequence with a nebulization dosimeter to deliver tenfold incremental concentrations of methacholine aerosol (mass median aerodynamic diameter = 1.52 micron; geometric standard deviation = 1.96) ranging from 0.025 to 25 mg/ml. When flow was unregulated, nebulizer output was not greater than when flow was regulated, but coefficients of variation of output were significantly greater (p less than 0.01). The PD20 on the two unregulated days was significantly different (p = 0.01), whereas the PD20 on the two flow regulated days was not significantly different (p greater than 0.05). We conclude that regulation of inspiratory flow rate at rates within the range of tidal breathing significantly decreases variability in nebulizer output and variation of pulmonary responses to methacholine challenge.     

BI-L-239, a 5-lipoxygenase inhibitor,blocks inhaled antigen-induced airway hyperresponsiveness in conscious guinea pigs

Male Hartley guinea pigs were actively sensitized to ovalbumin (OA). Respiratory system resistance (Rrs) was measured by forced oscillations superimposed on tidal breathing. Airway responsiveness (inhaled methacholine PC₁₀₀) was determined three days prior and three days after (day 10) three alternate day inhalations of OA. Airway cell composition was assessed on day 10 by lung lavage. Three groups (n=5–6) were studied: A) vehicle challenged, B) OA challenged/placebo treated, C) OA challenged/BI-L-239 (2,6-dimethyl-4-[2-(4-fluorophenyl)ethenyl]phenol) treated (10×0.75 mg/actuation, 10 minutes prior to each OA challenge). Animals were treated with pyrilamine and indomethacin (10 mg/kg i.p.) 30 minutes prior to each OA challenge. OA induced acute increases in Rrs of 143±29%, 238±73% and 102±43% in placebo and 86±34%, 45±35% (p, 0.05 vs. placebo) and 102±31% in BI-L-239 treated. OA induced a significant (p<0.05) increase in airway leukocytes in placebo (487±36 to 1615±421×10³/ml) but not BI-L-239 treated (to 881±155×10³/ml) and decrease in methacholine PC₁₀₀ in placebo (1.487±0.49 to 0.39±0.18 mg/ml) but not BI-L-239 treated (0.99±34 to 1.04±0.39 mg/ml). We conclude that BI-L-239 attenuates the airway constriction, inflammation and hyperresponsiveness induced by repeated antigen inhalations in conscious guinea pigs.     

The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma.

It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (approximately 60 L/min) versus low (approximately 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, greater than 1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (+/- SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 +/- 0.51 and 1.84 +/- 0.30, respectively (p less than 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 +/- 0.35 and 3.86 +/- 1.25, respectively, compared to 0.74 +/- 0.36 and 2.64 +/- 0.77 after slow inhalation (p less than 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of inhaled nifedipine on bronchial reactivity to histamine in man

We have administered nifedipine by aerosol to six patients with mild asthma to determine whether local administration of a potent calcium channel blocker has any effect on resting airway tone or histamine reactivity. Subjects had their responsiveness to histamine measured and then received either nifedipine, 10 mg in 40% ethanol, or diluent alone in a randomized, double-blind fashion. Specific airway conductance, blood pressure, and heart rate did not change after either inhalation. Histamine reactivity was significantly reduced after the nifedipine aerosol, the geometric mean provocative concentration causing a 35% fall in specific airway conductance, rising from 5.0 to 10.9 mg/ml of histamine (p less than 0.05). In individuals this protective effect was variable but overall was no greater than that observed after sublingual nifedipine. Plasma nifedipine concentrations were measured in two subjects after administration of the aerosol and confirmed that inhaled nifedipine is absorbed across the bronchial mucosa.     

The effect of inhaled allergen on circulating basophils in atopic asthma.

There is increasing evidence for the role of basophils in the allergen-induced late asthmatic response (LAR). To study the effect of inhaled allergen on basophil function in subjects with asthma, ex vivo basophil spontaneous histamine release (SHR) in peripheral blood and plasma histamine was measured before and 2, 5, 10, and 15 minutes, and 2, 4, 6, and 8 hours after allergen bronchial challenge (allergen study day) in six subjects with atopic asthma. Allergen inhalation induced an early response and LAR consisting of a mean (+/- SD) 32.5% (+/- 7.9%) and 28.8% (+/- 7.7%) fall in FEV1, respectively. As a control for the effects of bronchoconstriction, on another occasion, methacholine challenge was performed to produce a mean 33.4% (+/- 3.4%) fall in FEV1 during the early response and no LAR, and blood was obtained to measure basophil histamine release (HR) and plasma histamine. There was a small, but significant (p less than 0.05), rise in median SHR from 4.6% to 6.1% of total basophil histamine after allergen but not after methacholine inhalation. HR remained high after allergen inhalation during the 8 hours of study, whereas it demonstrated a steady, significant, decrease between 4 to 8 hours after methacholine inhalation. No significant changes in plasma histamine were recorded on either allergen or methacholine study days. On a third occasion, SHR was measured after challenge with physiologic saline to control for any effects of methacholine on SHR, and a decrease in HR was recorded during the day similar to HR observed after methacholine challenge. These studies suggest an enhancing effect of inhaled allergen on SHR.(ABSTRACT TRUNCATED AT 250 WORDS)