Histamine Bronchial Provocation Test Research Articles

Long-term prognosis of chronic cough: a prospective, observational cohort study

BackgroundThe long-term prognosis of chronic cough and its determinants need to be clarified.MethodsThis is a prospective, observational cohort study. Eighty-nine unselected subjects with chronic (> 8 weeks’ duration) cough were carefully investigated: Clinical examination, symptom questionnaire, Leicester Cough Questionnaire (LCQ), skin prick tests, ambulatory peak expiratory flow monitoring, spirometry before and after 0.4 mgs of salbutamol, exhaled nitric oxide concentration measurement, hypertonic saline cough provocation test, and histamine bronchial provocation test. After five years, a letter was sent to the subjects containing questions about continuation of cough, smoking, indoor exposures, presence of co-morbidities, and current medication. It also contained LCQ and Cough Clinic diagnostic questionnaire. Sixty-eight subjects (76%) responded.ResultsAt five years, continuing regular cough was present in 31 (46%) of the subjects and continuing impairment in cough-related quality of life (less than 1.3 points’ improvement in LCQ) in 32 (47%). Continuing regular cough was associated with presence of chronic rhinitis or esophageal reflux disease, baseline mild airway responsiveness to histamine, and baseline strong cough responsiveness to hypertonic saline. Continuing impairment in cough-related quality of life was associated with high body mass index, absence of atopy, absence of pets, and high number of background disorders (esophageal reflux disease, asthma, or chronic rhinitis).ConclusionsAlmost half of subjects with chronic cough suffered of the disorder at five years from initial assessment. Several possible determinants of poor prognosis could be identified.

Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in patients suffering from bronchial asthma

Physical activity is a common stimulus of asthmatic symptoms manifestation. Airway hyperreactivity is a predisposing cause of exercise induced bronchial obstruction, diagnosed by histamine inhalation. The aim of this study was to determine the relation between the amounts of histamine needed to induce non-specific airway hyperreactivity and exercise-induced bronchial obstruction. This randomized cross-over study included 160 male patients (age 19-27 years) suffering from bronchial asthma who showed positive results as the reaction after the histamine bronchial provocation test. Histamine concentrations were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise stress test conducted on a conveyor belt. The results of the exercise stress test were considered positive if the FEV1 level dropped by at least 15% from its initial value, 5-10 minutes after the test. All the patients showed positive results as the reaction after the histamine bronchial provocation test, while 50 of them showed positive results after the exercise-induced stress test. There was a statistically highly significant difference in administrated histamine concentrations between the group of patients that had positive results on exercise stress test and those who did not (1 mg/mL vs 0.5 mg/mL; U = 1678; p < 0.01). Also, there was a statistically significant difference concerning the frequency of the positive results regarding histamine concentration after induced stress test (chi2 = 10.885; p = 0.001). Among the patients with positive results, there was a statistically highly significant number of patients with bronchial obstruction induced by less than 2 mg/mL of histamine (p < 0.01). A statistically significant relation between the amount of histamine needed to induce bronchial obstruction and the results of the exercise stress test (p < 0.01) was also observed after the testing. In the group of patients with positive results after the exercise-induced stress test, there were significantly more patients with positive results to non-specific bronchial provocation test with lower histamine concentrations. Histamine concentrations needed to induce non-specific hyperreactivity of asthmatic airway were shown to be related to the reactivity to physical effort.

Environmental and occupational respiratory diseases – 1042. Influence of environmental endotoxin and allergen levels on prevalence of asthma and allergen sensitizations in urban and rural children in Guandong, China

Methods Three hundred and seventeen children aged 13-14 years (Guangzhou 188, Conghua 129) with self-reported respiratory symptoms and 537 healthy children were selected from 854 school-children according to their response to ISAAC standardized questionnaire. These children attended the school infirmary again to complete a detailed questionnaire and medical examinations including skin prick test (SPT) to 8 common aeroallergens, lung function test, histamine bronchial provocation test and peripheral blood eosinophil counts. House dust samples were collected from living room and mattresses of 156 of these children with the agreement of their parents (Guangzhou 76, Conghua 80). The content of endotoxin in house dust was quantified using an endpoint chromogenic kinetic limulus amoebocyte lysate test. Associations between levels of house dust allergens and endotoxin and the provocation dose producing a 20% fall in forced expiratory volume in one second (PD20-FEV1) and allergen skin reactions were analysed by logistic regression. Results The prevalence of wheeze symptom, asthma, nasal symptoms and allergic rhinitis in the children of Guangzhou were significantly higher (28.6%, 27.7%, 66%, 46.4%, respectively) than the children of Conghua (5%, 2.5%, 31%, 6.2%, respectively, p<0.01). Endotoxin concentrations in dust samples in homes of Conghua were significantly higher (1794 EU per square meter, 10.95 EU endotoxin/g dust) than those of Guangzhou (508.8 EU per square meter, 6.45 EU endotoxin/g dust, p<0.01). Logistic regression analyses showed a positive association between endotoxin levels and PD20-FEV1 (r=0.174, p<0.05), and a negative association (p<0.01) between endotoxin levels and the wheal sizes of skin response to Dermatophagoides pteronyssinus (Der. p) and Dermatophagoides farinae (Der. f).

Association Between Chronic Colonization or Infection With Pseudomonas aeruginosa and Bronchial Hyperreactivity in Patients With Cystic Fibrosis

In patients with cystic fibrosis, bronchial hyperreactivity is a common finding that has not been conclusively associated with atopy. The objective of the present study was to determine the relationship between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in a group of patients with cystic fibrosis. A nonspecific histamine bronchial provocation test was administered to a group of 32 cystic fibrosis patients with a mean (SD) age of 11.25 (3.7) years. The presence of atopy and of chronic colonization or infection with P aeruginosa was also studied. Nine of the 32 patients (28.1%) studied showed bronchial hyperreactivity. The clinical status of these 9 patients was significantly worse and all were colonized or infected with P aeruginosa. Atopy was present in 17 of the 32 patients (53.1%) in the study group, but in only 3 of the 9 patients (33.3%) with bronchial hyperreactivity. Bronchial hyperreactivity was significantly associated with colonization or infection with P aeruginosa (P< .001), but not with atopy (P=.12). In the patients without atopy, colonization was significantly associated with bronchial hyperreactivity (P=.017). In the group with normal lung function (forced expiratory volume in 1 second >/=80%) this association was also significant (P=.044), while the association between bronchial hyperreactivity and atopy was not (P=.11). The results of the present study suggest that in patients with cystic fibrosis, bronchial hyperreactivity may be associated with colonization or infection with P aeruginosa, and that this may be a more important risk factor for bronchial hyperreactivity than atopy.

Does Experience Influence Perception of Dyspnea?

The perception of somatic sensations like dyspnea can be influenced by such factors as an individual s personality, experiences, or ability to adapt to stimuli. Our aim was to determine whether the perception of acute bronchoconstriction is different for patients with asthma and patients who have never experienced an episode of airway obstruction. We studied 2 groups of patients. The first consisted of 24 subjects with intermittent rhinitis and asthma (10 females and 14 males) with a mean (SD) age of 25 (7) years. All reported not feeling dyspnea at rest on a Borg scale. The second group consisted of 24 subjects who only had rhinitis but no lung disease (no episode of asthma) or dyspnea at rest (12 females and 12 males) with a mean age of 27 (6) years. There were no significant differences between the groups with regard to sex, smoking, economic or educational level, anxiety (determined by the trait portion of the State-Trait Anxiety Inventory), depression (Beck Depression Inventory), or spirometric parameters. All took a histamine bronchial provocation test in which the patient assessed dyspnea on a modified Borg scale after each histamine dose. The provocation dose needed to produce a 20% decrease (PD20) in forced expiratory volume in the first second (FEV1) was calculated. We also recorded dyspnea perception score when FEV1 fell 5%, 10%, 15%, and 20%. No dyspnea was perceived at PS20 by 12.5% of the asthmatics and by 45% of nonasthmatics (P< .0001). The mean PS20 was 2.4 (2.1) (range, 0-7) in the first group and 0.37 (0.48) (range, 0-3) in the second (P< .0001). More asthma patients than nonasthmatics perceived dyspnea at all degrees of bronchial obstruction. PD20 was different in the 2 groups (1.6 [2] vs 6.03 [5] for the first and second groups, respectively; P< .003), but there was no significant relation between PD20 and PS20 (Spearman s correlation coefficient, 0.19; P= .221). Our findings support the hypothesis that appropriate perception of dyspnea is grounded in prior experience and learning.

Objective Assessment of Lower Airway Involvement in Chronic Rhinosinusitis

When associated with lower airway involvement, the morbidity and the cost of chronic rhinosinusitis (CRS) can increase. The aim of this prospective study was to assess the clinical and radiological characteristics of the upper airways in CRS patients scheduled for functional endoscopic sinus surgery and to correlate these findings with the functional changes of the lower airways. Twenty-five adult patients with CRS were subjected to clinical and endoscopic assessments, computed tomography scan, and allergic assessments using validated scoring systems. Lower airways were assessed by clinical history, pulmonary function test, histamine bronchial provocation test, and chest x rays. Sixty percent of CRS patients were shown to have associated lower airway involvement, i.e., 24% had asthma and 36% had small airway disease (SAD). Nasal congestion and nasal polyps were the most common clinical findings in both of these subgroups of patients. In addition, there was a negative correlation between computed tomography scan findings of the sinuses and the obstructive parameters on pulmonary function test in SAD but not in the asthma subgroup. These results showed that different kinds of lower airway involvement frequently could be associated with CRS. Some are manifest such as asthma and some are hidden such as SAD and histamine bronchial hyperresponsiveness.

Respiratory Function Changes in a Wilderness Multisport Endurance Competition: A Prospective Case Study

To document serially and in detail the changes in respiratory function during competition in a typical wilderness multisport endurance athlete. Prospective observational case study over two years during a 105 km wilderness multisport endurance competition consisting of cross country skiing, cross country running, cycling, and whitewater canoeing. Nedocromil prophylaxis was used during the second year of the study only. FEV1, FVC, flow volume loops, and oxygen saturation were measured serially during the race. Baseline spirometry and histamine bronchial provocation tests were normal. SaO2% decreased to a minimum of 92%. Decreases in both FEV1 (up to 25%) and FVC (up to 22%) were observed at race finish in both years. Although FEV1/FVC ratios only decreased marginally, the pattern of change in maximum expiratory flow rates was most consistent with evolving airflow obstruction. The changes were not prevented by nedocromil. The subject did not develop symptomatic wheezing or abnormal breathlessness and finished the event without incident. Ultra endurance multisport competition may induce substantial changes in respiratory function. These appear to be attributable to evolving airflow obstruction.

Perception of Respiratory Sensation Assessed by Means of Histamine Challenge and Threshold Loading Tests

Some asthmatic patients perceive the severity of their disease rather poorly. These patients may not receive optimal therapy because of underpresentation of their respiratory symptoms. It is therefore important to identify these patients. The present study evaluates a new threshold loading device for measuring the perception of respiratory sensation. This method for measuring the perception of respiratory sensation may be a viable alternative to the bronchial provocation test. The aim of the present study was to investigate whether the assessment of the perception of respiratory sensation based on a threshold loading test (inspiratory and expiratory) identifies the same subjects as poor perceivers as compared to assessment by histamine bronchial provocation test. In 36 subjects, the perception of respiratory sensation through a threshold loading device was compared to the perception of respiratory sensation during a histamine provocation test. Each test was performed with scoring of the magnitude of the respiratory sensation on a visual analog scale (VAS). The magnitude of the stimulus intensity was indicated by the percentage of decrease in FEV(1) during the histamine challenge test and by the percentage of the subject's maximum mouth pressure (percent maximal inspiratory pressure and percent maximal expiratory pressure) during the threshold loading test. The relationship between VAS values and the stimulus intensity was analyzed by determining the linear regression coefficient between the two parameters. No relationship was found between the perception of the sensation induced by the histamine challenge and that during breathing through a threshold loading device for both inspiration (Rs = 0.15; p = 0.40) and expiration (Rs = 0.13; p = 0.47). We did find a significant relation between the perception of respiratory sensation during the inspiratory and expiratory threshold loading test (Rs = 0.67; p = 0. 0001). Furthermore, we defined a subgroup of patients of special interest: those with low symptoms of breathlessness and high bronchial responsiveness. Compared to the inspiratory and expiratory threshold loading test, the histamine challenge test identified more patients in the special interest group as poorest perceivers. The measurement of perception by means of a threshold loading device and a histamine provocation test did not identify the same subjects as poor perceivers, probably because we did not measure the patient's perceptiveness for exactly the same stimuli. In the population with relatively more severe asthma and very low symptoms of breathlessness, the histamine-induced bronchoconstriction test identified more patients as poorest perceivers compared to the threshold loading test.

Analysis of tidal expiratory flow pattern in the assessment of histamine-induced bronchoconstriction.

There are times in clinical practice when it would be useful to be able to assess the severity of airways obstruction from tidal breathing. Three indices of airways obstruction derived from analysis of resting tidal expiratory flow have previously been described: (1) Tme/TE = time to reach maximum expiratory flow/expiratory time; (2) Krs = decay constant of exponential fitted to tidal expiratory flow versus time curve; and (3) EV = extrapolated volume--that is, area under the curve when the fitted exponential is extrapolated to zero flow. In this paper a further index--dtr/TE, time from the beginning of expiration till the rapid decay of flow begins/expiratory time--is evaluated. The aim of this study was to assess the ability of these indices to detect mild airways obstruction. A histamine bronchial provocation test was performed in 20 adult patients with a diagnosis of asthma or symptoms of cough and/or shortness of breath. Baseline forced expiratory volume in one second (FEV1), functional residual capacity (FRC), and specific inspiratory conductance (sGaw) were measured and the measurements repeated after the final inhalation of histamine. Expiratory flow patterns during quiet breathing over five consecutive representative breaths were analysed before and after histamine. The test was concluded in 12 subjects when FEV1 had decreased by 20% of the post saline value, and in the remaining eight after inhalation of 16 or 32 mg/ml histamine. FEV1, sGaw, FRC, Krs, EV, and dtr/TE were all different after histamine (paired t test). For Tme/TE no difference was shown. Change in EV detected change in end tidal volume but underestimated it compared with the change measured by body plethysmography. Percentage fall in Krs after histamine correlated with percentage fall in FEV1 (r = 0.527, Pearson correlation coefficient). This was of a similar order to the correlation between the percentage fall in sGaw and in FEV1 (r = 0.543). Analysis of expiratory tidal flow-time patterns predicted a decrease in FEV1 following histamine challenge as did measurement of sGaw. This analysis of tidal breathing would be useful in circumstances where forced expiratory manoeuvres are unreliable or inapplicable.

Histamine Bronchial Provocation Test: Timed Tidal Breathing Technique

Background The measurement of nonspecific bronchial hyperreactivity is valuable for diagnosis and management of bronchial asthma. Methacholine or histamine is used for the pharmacologic provocation test. Usually a methacholine bronchial provocation test is performed by a dosing technique with counted number of breaths. A dosimeter is indispensable in the dosing technique. Recently a timed tidal breathing technique which dose not need an expensive dosimeter was introduced. We measured the degree of nonspecific bronchial hyperreactivity to histamine using a simple timed tidal breathing technique. Method Forty two healthy volunteers, 12 patients with bronchial asthma(BA), 10 patients with rhinitis(RH) and 10 patients with upper respiratory infection(URI) participated in the study. The subject's nose was clipped and inhalation continued during tidal breathing for 2 minutes via a face mask. FEV1 was measured at 30 seconds, 90 seconds after inhalation and inhalation of next solution was continued until there was a fall in FEV1 of 20%. Histamine PC20 was defined as the concentration at 20% fall of FEV1 and it was obtained from the log dose-response curve by linear interpolation. Results Inhalation of serial dilution of histamine could be performed in all patients without significant side of effects. The geometric mean±standard deviation of histamine PC20 in healthy volunteers is 8.27±2.22mg/ml, BA group 0.33±3.02mg/ml, RH group 0.85 ±3.24mg/ml, and URI group 1.47±1.98mg/ml. Conclusion Histamine bronchial provocation test using timed tidal breath method is a simple and suitable tool for management of patients with bronchial hyperreactivity.

Bronchial hyperresponsiveness in young students of southern China: relation to respiratory symptoms, diagnosed asthma, and risk factors.

A cross sectional study was carried out to determine the prevalence of bronchial hyperresponsiveness and asthma in 3067 students aged 11-17 years in an urban and a rural area of Guangzhou (Canton), China. The methods used included a self administered questionnaire, a histamine bronchial provocation test, and allergen skinprick tests. Bronchial hyperresponsiveness was defined as a 20% fall in FEV1 and peak expiratory flow at a provoking dose of histamine (PD20) less than 7.8 mumol on two occasions four weeks apart. The response rate was 98.0% and 99.2% in the two areas. The prevalence of bronchial hyperresponsiveness was 4.1% and of diagnosed asthma 2.4% in the total population. There were no significant differences in prevalence between the urban and the rural area or between boys and girls. The 11-12 year group had a higher prevalence of bronchial hyperresponsiveness (7.6%) than the older groups. Of the 125 with bronchial hyperresponsiveness, 12.0% were defined as having severe or moderate (PD20 less than 0.8 mumol), 26% mild (0.9-3.2 mumol), and 62% slight bronchial hyperresponsiveness (3.3-7.8 mumol). The severity of bronchial hyperresponsiveness was closely related to diagnosed asthma, wheezing, and cough, though half the students with bronchial hyperresponsiveness were symptom free. The most common allergens were house dust and house dust mite in the city, and hay dust, pollen, and feathers in the rural area. The odds ratios for having respectively slight, mild or moderate, and severe bronchial hyperresponsiveness were 5.9, 21.0, and 30.4 for atopy; 1.9, 1.9, and 7.3 for early respiratory infection; and 3.1, 2.5, and 5.6 for a history of parental asthma.

Increased bronchial responsiveness to histamine associated with shortened inhalation time

A study was undertaken to assess the variability of results of histamine inhalation tests with the tidal breathing method, keeping the total dose of histamine delivered to the mouth constant but using either different nebulizers or the same Wright nebulizer operated under changing conditions. Seventeen asthmatic children had double histamine bronchial provocation tests with a Bennett-Twin nebulizer (output 0.31 ml/min, nebulization time 1 min) and a Wright nebulizer (output 0.15 ml/min, nebulization time 2 min), with a driving flow rate, in both instances, of 7 L/min. Another group of 15 asthmatic children had double provocation tests with a Wright nebulizer driven by a flow rate of either 7 L/min (output 0.15 ml/min, nebulization time 2 min) or 12 L/min (output 0.30 ml/min, nebulization time 1 min). In each experiment the volume of histamine solution delivered was about 0.30 ml. PC20-FEV1 was significantly lower, indicating an increased bronchial response, when both methods using "faster" delivery of histamine were used. We conclude that comparison of results obtained with histamine inhalation tests by the tidal breathing method cannot be made unless the nebulizer and operating criteria are the same.

Clinical, physiologic, and psychologic comparison of treatment by cromolyn or theophylline in childhood asthma

Treatment of chronic perennial childhood asthma with cromolyn sodium (CS) or long-acting theophylline (LAT) was compared in 13 children by a double-blind, cross-over trial in which each drug was administered for 4 wk. LAT was administered twice daily in individual doses to elicit adequate blood levels (mean 14.0 ± 1.6 SEM, micrograms per milliliters). Powdered CS was administered by inhalation in a dose of 20 mg four times daily. The patients were followed by means of a daily symptom and drug consumption diary and twice daily peak flow measurements. A series of psychologic studies were performed in the third week of each month. Exercise and histamine bronchial provocation tests were performed at the end of each month. There were no significant differences between the month in which CS was taken and the month in which LAT was taken in terms of diary scores, peak flow rates, additional drug consumption, or in bronchial reactivity to exercise or histamine at the end of each month. The results of psychologic tests reflecting visual-spatial planning were significantly better for the four children receiving CS with lower IQ scores (87 to 105) but not for the nine children with higher IQ scores (111 to 134). The possibility that the psychologic performance of children with lower intelligence may be adversely affected by theophylline requires further evaluation.