Changes In Bronchial Responsiveness Research Articles

Postmenopausal hormone therapy and asthma-related hospital admission

There is considerable evidence that female sex hormones are involved in the asthma pathogenesis. Asthma is most prevalent in boys during childhood but after puberty it is more common in females. Also, changes in bronchial responsiveness and asthma symptoms have been demonstrated in relation to the menstrual cycle.1 These findings suggest that treatment with exogenous sex hormones, such as postmenopausal hormone replacement therapy (HRT), may affect the risk for asthma morbidity, and this is supported by several observational studies showing increased asthma prevalence and incidence in women using HRT.

CPAP increases bronchial reactivity in OSAS patients

Continuous positive airways pressure (CPAP) is a well known and safe method of treatment patients with obstructive sleep apnoea syndrome (OSAS). The effects of CPAP administration on the upper respiratory tract are known. However its effects on the lower respiratory tract still needs to be determined. Studies on bronchial hyperreactivity in patients treated by CPAP are contradictory. The aim of the study was to assess the influence of a 3-week CPAP treatment in patients with OSAS and to evaluate associations between changes in bronchial reactivity and clinical features of OSAS and lung function tests (LFT). Patients with newly diagnosed OSAS and lack of infection or chronic illness of the respiratory tract or other conditions which could influence bronchial hyperreactivity (BHR) were included. Investigations were performed in 101 patients. There were 88 males and 13 females, mean age 51.5±11.2 years and BMI 32.6±5.4 kg·m⁻². Qualified patients were randomly divided into 2 groups: 76 patients to CPAP treatment group, 25 control group. Both groups did not differ in anthropometrics features, severity of OSAS and LFT. Metacholine challenge test (MchCT) was performed at baseline and repeated after 3 weeks. Analysis of the individual results showed that in 11 patients the MchCT was positive (6 in the CPAP and 5 in the control groups). After 3 weeks in the group of CPAP treated patients an increase of BHR was noted. Log PC20M decreased from 1.38±0.3 to 1.26±0.5 (p<0.05). The number of patients with a positive result in the MchCT increased from 6 to 16 patients. There was no significant change in BHR in the control group. It was found that CPAP treated patients with BHR were older, had less severe OSAS and lower FEV1 (p<0.05). In none of the patients positive result of BHR did no affect compliance to CPAP treatment. Conclusions: CPAP therapy increases bronchial reactivity, but does not affect compliance to treatment.

Longitudinal changes of pulmonary function and bronchial responsiveness in cough-variant asthma treated with bronchodilators alone

Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as beta 2 adrenergic agonists. The aim of this study was to assess longitudinal changes of pulmonary function and bronchial responsiveness in CVA, which was treated with bronchodilators alone. Seventeen CVA patients recorded intensity and frequency of cough every day. Spirometry and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20) were measured in the run-in period and after cough almost completely relieved on therapy. Cough score had improved within 2 weeks after the initiation of bronchodilator therapy. Forced expiratory volume in one second (FEV1) was significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L after improvement of cough. However, the geometric mean (GSEM) PC20 value did not change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial responsiveness in CVA does not improve when only bronchodilator therapy is carried out. Because bronchial hyperresponsiveness has been shown to be a risk factor for typical asthma onset from CVA, the effect of inhaled corticosteroids on the longitudinal changes in bronchial responsiveness should be examined.

Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness

BackgroundAn increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma.MethodsBALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase.ResultsIntratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia.ConclusionOur data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma.

An Increase in Bronchial Responsiveness Is Associated with Continuing or Restarting Smoking

Bronchial responsiveness (BHR) has been found to be associated with smoking, atopy, and lower lung function in cross-sectional studies, but there is little information on determinants of change in adults. To analyze change in bronchial responsiveness in an international longitudinal community study. The study was performed in 3,993 participants in the European Community Respiratory Health Survey who had bronchial responsiveness measured in 1991-1993, when aged 20 to 44 yr, and in 1998-2002. Bronchial responsiveness was assessed by methacholine challenge. Serum samples were tested for total IgE, and for specific IgE to four common allergens. Smoking information was obtained from detailed administered questionnaires. Change in bronchial responsiveness was analyzed by change in IgE sensitization, smoking, and lung function, with tests of interaction terms with age and sex. Continuing and restarting smokers had increasing bronchial responsiveness, approximately equivalent to a mean reduction in PD20 of 0.68 and 0.75 doubling doses, respectively, over 10 yr, in addition to a small increase explained by decline in FEV1. No other risk factor for change in bronchial responsiveness was identified. Smoking is a risk factor for increasing bronchial responsiveness over and above the effect of decreasing lung function. Neither baseline IgE sensitization nor change in sensitization was shown to be a risk factor for increasing BHR, the latter possibly due to little overall increase or decrease in sensitization.

Change in bronchial responsiveness and cough reflex sensitivity in patients with cough variant asthma: effect of inhaled corticosteroids

BackgroundCough variant asthma (CVA) is a cause of chronic cough and a precursor of typical asthma. We retrospectively examined the longitudinal change in bronchial responsiveness and cough reflex sensitivity in CVA patients with respect to the effect of long-term inhaled corticosteroids (ICS).MethodsProvocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20-FEV1) and provocative concentration of capsaicin eliciting 5 or more coughs (C5) were measured before treatment and during a follow up period following relief of cough (median; 2.0 (range; 0.5 to 8.0) years after the initial visit) in a total of 20 patients with CVA (7 males and 13 females, mean ± SD age of 49.9 ± 12.9 years).ResultsThree of 8 patients not taking long-term ICS developed typical asthma compared to none of 12 patients taking ICS (p = 0.0171). PC20-FEV1 significantly (p < 0.0001) increased from 1.80 (GSEM, 1.35) to 10.7 (GSEM, 1.63) mg/ml in patients taking ICS but did not change in patients not taking ICS [2.10 (GSEM, 1.47) compared to 2.13 (GSEM, 1.52) mg/ml]. Cough threshold did not change in patients whether taking or not taking ICS.ConclusionLong-term ICS reduces bronchial hyperresponsiveness in CVA as recognized in typical asthma. Cough reflex sensitivity is not involved in the mechanism of cough in CVA.

Virus‐provoked rhinitis and asthma in allergic patients

SummaryRhinovirus, influenza, parainfluenza or respiratory syncytial virus not only provoke upper respiratory tract infections (URI) but also can precipitate asthma in adults and children, many of whom also manifest allergic respiratory disease. It has been postulated that patients with allergic rhinitis experience more pronounced symptoms and pathophysiology during URI than individuals without allergy. These observations have provided limited insight into the pathogenesis of URI in allergic patients. To better define these relationships several groups of investigators have examined the effect of experimental virus infection on volunteers with and without allergic rhinitis and with and without asthma. Lemanski et al. showed that Rhinovirus 16 (RV16) was able to modify bronchial hyperreactivity and late phase allergic asthmatic reactions. Calhoun et al. demonstrated that RV16 potentiated airway inflammation after segmental allergen bronchoprovocation in allergic subjects. Experimental RV16 infection also provoked a modest increase in histamine responsiveness accompanied by a modest increase in bronchial and intranasal lymphocytes and eosinophils. Yet, experimental RV16 infection did not trigger asthma or changes in spirometry or changes in bronchial reactivity to histamine or bradykinin in normal subjects. Studies in our laboratories using experimental Rhinovirus 39 (RV39) infection did not alter pulmonary measurements or methacholine responses in normal healthy allergic subjects. These results were surprising, as enhanced WBC histamine release was observed in the same RV39‐infected allergic subjects and was similar to that observed in RV16 infection described by others. The RV39‐infected allergic subjects also showed acute increases in serum IgE as well as changes of cellular immune parameters. Bardin et al. described more severe nasal symptoms as well as increased nasal albumin in allergic rhinitis subjects experimentally infected with RV16. However, allergic subjects infected with RV39 did not show a physiologic hyper‐responsiveness during a nonallergy season. Analysis of nasal secretions during RV39 infection did show more vascular permeability in allergic subjects. Experimental infection with RV39 and Influenza A has provoked eustachian tube obstruction, otitis media and rarely acute otitis. These studies of volunteers experimentally infected with virus suggest that atopy alone does not predispose to more severe symptoms but combining URI with allergen exposure enhanced allergen‐induced inflammation. Recent studies implicate cytokines as participants in these virus‐provoked responses. Increases in nasal lavage concentrations of IL‐6 were found during experimental URIs caused by RV39, Influenza A and respiratory syncytial virus and coincide with peaks in symptomatology and pathophysiology. Moreover, IL‐6 applied directly to the nasal mucosa in noninfected allergic subjects reproduced symptoms of rhinitis. Other studies have shown that IL‐10 secretion from peripheral blood white cells was impaired in allergic subjects after experimental infection with Influenza A. It is anticipated that future studies using natural infection as well as experimental virus infection model will further define the mechanisms and relationships of virus infection to allergy and asthma.

Effect of a cysteinyl leukotriene antagonist, pranlukast hydrate, on acetaldehyde-induced bronchoconstriction in asthmatic patients

Acetaldehyde is a main factor of alcohol-induced asthma. We previously reported that the cysteinyl leukotriene (cys-LT) receptor antagonist, pranlukast hydrate, inhibits acetaldehyde-induced airway hyperresponsiveness in guinea pigs. The purpose of this study was to evaluate the involvement of cys-LT on bronchial responsiveness to acetaldehyde in asthmatic patients. We investigated the bronchial response to inhalation of acetaldehyde in 10 asthmatic patients, who were treated with placebo or pranlukast hydrate (225.5 mg), a cys-LT receptor antagonist, twice a day for 1 wk using a double-blind, randomized, placebo-controlled, cross-over design. Although a remarkable improvement of acetaldehyde bronchoconstriction was observed in 3 out of 10 subjects, PC20-AcCHO values were identical between placebo [12.0 (GSEM, 1.192) mg/ml] and pranlukast [14.7 (GSEM, 1.245) mg/ml] groups. The changes in bronchial responsiveness to acetaldehyde were similar in the six patients who had never experienced alcohol-induced asthma and the four who had. In conclusion, cys-LTs are not involved in acetaldehyde-induced bronchoconstriction.

Longitudinal Changes in Bronchial Responsiveness Associated With Swine Confinement Dust Exposure

Acute exposure to the air in swine confinement units causes bronchial hyperresponsiveness and inflammation of the airways. This study was performed to assess the longitudinal development of bronchial responsiveness in pig farmers and to establish exposure-response relationships. A cohort of 171 pig farmers was followed over a 3-year period. Bronchial responsiveness was assessed by a histamine provocation test. Long-term average exposure to inhalable dust and endotoxin was determined by personal monitoring in summer and winter, using data on farm characteristics and activities. Time-weighted average (TWA) personal exposure to ammonia was measured. Data on farm characteristics were gathered in the same period. Mean increase in responsiveness was 2.52 doubling concentrations of histamine for a 10% decrease in FEV(1) and 1.36 doubling concentrations for a 20% decrease in FEV(1). Long-term average exposure to dust was 2.63 mg/m(3) and to endotoxin was 105 ng/m(3). TWA exposure to ammonia was 1.60 mg/m(3). After adjusting for age and smoking behavior, long-term average exposure to inhalable dust was associated with increases in bronchial responsiveness expressed as steps for provocative concentration causing 10% fall in FEV(1). TWA exposure to ammonia, use of wood shavings as bedding, and automated dry feeding were associated with increases in responsiveness expressed as steps for provocative concentration causing a 20% fall in FEV(1). Exposure to dust and ammonia in pig farms contributes to chronic inflammation of the airways and should be reduced.

Prednisolone Hastens Recovery from Histamine-Induced Bronchospasm in Asthmatics

Short-term treatment with oral steroids is very effective in controlling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV1] and concentration of histamine causing a 20% reduction FEV1 [PD20 FEV1]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD20 FEV, values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean ± SD time for 95% recovery from histamine-induced bronchospasm was 33.00 ± 19.47 min before treatment and decreased significantly to 18.00 ± 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.

Chronic rhinitis in workers at risk of reactive airways dysfunction syndrome due to exposure to chlorine.

BACKGROUND: To assess the frequency of chronic upper airways symptoms and to relate the presence of these symptoms to accidental exposure to chlorine and changes in lower airways symptoms, airway...

Change in airway responsiveness among apprentices exposed to metalworking fluids.

To investigate early pulmonary responses to metalworking fluid exposure, we enrolled first-year machinist apprentices and apprentices in three other trades into a 2-yr longitudinal study. We obtained complete data for 82 machinists and 159 control subjects. Tests included respiratory questionnaires, spirometry, methacholine challenge, and allergy skin tests. Details on duration of exposure were collected by interview and 68 representative full shift personal samples for "total aerosol" were obtained from 13 shops (mean: 0.46 mg/m3, range: < 0.7 to 3.65 mg/m3). Machinists and control subjects did not differ at baseline. At follow-up, average change in bronchial responsiveness was double in machinists compared with control subjects (p = 0.05), and machinists were more likely to have developed new bronchial hyperresponsiveness (BHR) with asthmalike symptoms. In linear regression analysis, for predictors of methacholine slope, increased BHR was associated with duration of exposure to both synthetic and soluble metalworking fluids (p < 0.05); in logistic regression analysis, for predictors of BHR, only duration of exposure to synthetic fluids was a significant predictor. Results were not changed when workers with PC20 < 8 mg/ml at baseline were excluded. We conclude that exposure to water-based metalworking fluids (especially synthetic fluids) is associated with increasing BHR during the first 2 yr of exposure.

Relationship between acute ozone responsiveness and chronic loss of lung function in residents of a high-ozone community.

We hypothesized that acute respiratory responsiveness to ozone predicts chronic lung injury from repeated exposure to ozone-containing air pollution. We tested this hypothesis in 164 middle-aged nonsmoking residents of an ozone-polluted community who underwent lung-function measurements during 1986 and 1987 (i.e., time 3). The time-3 study was a follow up of more comprehensive studies conducted in 1977-1978 (time 1) and in 1982-1983 (time 2). In contrast to the apparent rapid (i.e., approximately 60 ml/y) decline in lung-function measurements between times 1 and 2, our subjects showed little change in forced vital capacity (FVC) or forced expired volume in 1 s (FEV1.0) between times 2 and 3, and they experienced a normal decline between times 1 and 3. A subgroup (n = 45) underwent 2-h laboratory ozone exposures to 0.4 ppm ozone, accompanied by intermittent exercise, and they experienced mild acute reductions in FEV1.0 and FVC, but there was little change in bronchial responsiveness to methacholine. Individual acute responses to laboratory ozone were not correlated with individual long-term changes between times 1 and 3. In summary, the results did not support our initial hypothesis, and they did not confirm rapid function decline in nonsmokers chronically exposed to ozone-containing air pollution.

Assessment of food chemical intolerance in adult asthmatic subjects.

Identification of food chemical intolerance in asthmatic subjects can be reliably assessed by changes in the forced expiratory volume in one second (FEV1) in response to double blind, placebo controlled challenges on a strict elimination diet. However, this method is cumbersome and time consuming. A study was undertaken to determine whether changes in bronchial responsiveness to histamine following food chemical challenge without an elimination diet might be a faster, more convenient method. Eleven adult asthmatic subjects were challenged twice with metabisulphite, aspirin, monosodium glutamate, artificial food colours, sodium nitrite/ nitrate, 0.5% citric acid solution (placebo), and sucrose (placebo) on separate days. During the first set of challenges subjects consumed a normal diet. Bronchial responsiveness to histamine was assessed 90 minutes after each challenge. A greater than twofold increase in bronchial responsiveness was considered positive. For one month prior to and during the second set of challenges subjects followed a strict elimination diet and FEV1 was monitored during and for two hours after each challenge. A fall in FEV1 of 20% or more was considered positive. Of the 77 food chemical challenges performed on an unmodified diet, 20 were positive (six placebo responses). In two subjects it was not possible to perform a histamine test after one of the chemical challenges because of poor spirometric function. Of the 77 food chemical challenges performed on an elimination diet, 11 were positive (no placebo responses). Excluding the two challenges in which there were no corresponding histamine tests, only on two occasions did the positive responses in both methods coincide, giving the unmodified diet method a sensitivity of 22%. Strict dietary elimination and measurement of FEV1 after double blind food chemical challenge remains the most reliable method for the detection of food chemical intolerance in asthmatic subjects.

Allergic sensitization is associated with increased bronchial responsiveness: a prospective study of allergy to laboratory animals

The purpose of this prospective study was to investigate the extent of change in bronchial responsiveness and the prognostic value of methacholine provocation in early sensitization to laboratory animals. Thirty eight laboratory technicians were studied during training (before first exposure) and after having been exposed to laboratory animals for a median 18 (range 5-33) months. On both occasions they were subjected to spirometry, bronchial methacholine challenge, skin-prick tests and blood sampling, and responded to questionnaires. Nine (24%) developed laboratory animal allergy (LAA), defined as animal work-related symptoms (n = 8), or specific immunoglobulin E (IgE) (n = 7) or both. In the LAA group, bronchial responsiveness was normal before employment, but had increased significantly at follow-up compared to technicians who had not developed LAA. Six of the nine LAA subjects had a more than threefold increase in bronchial responsiveness, and three of these reported chest symptoms. Spirometric values were not different between the groups prior to exposure or at follow-up, and had no prognostic value. However, a pre-employment level of total IgE > 100 kU.L-1 predicted the development of LAA (relative risk 2.8). Thus, early LAA was associated with increased bronchial responsiveness in most subjects. In contrast to total IgE, the level of pre-employment bronchial responsiveness or lung function did not influence the magnitude of change in responsiveness, nor predict sensitization.

Age-related changes in bronchial hyperreactivity to methacholine in asthmatic children.

To evaluate the influence of aging on bronchial hyperreactivity (BHR) during the childhood period, age-related changes in bronchial reactivity to methacholine (BRm) in children from 2 to 13 yr of age were studied using the same method, employing a methacholine inhalation challenge with transcutaneous oxygen pressure (tcPO2) monitoring. Three hundred and thirty-nine asthmatic subjects (male:female = 200:139, aged [mean +/- SEM] 7.2 +/- 0.2 yr) and 107 age-matched controls (male:female = 55:52, aged 5.3 +/- 0.3 yr) were enrolled in this study. TcPO2 was measured by a tcPO2 monitor, and subsequent doses of methacholine were then doubled until a 10% decrease in tcPO2 from its baseline value was reached. The cumulative dose of methacholine at the inflection point of tcPO2 (Dmin-PO2) was considered to represent the BRm. For the sake of comparison, respiratory resistance (Rr) in subjects more than 6 yr old was measured by the oscillation technique during methacholine inhalation challenge, and the threshold point of Rr (Dmin-Rr) was also considered to represent the BRm. In the asthmatic children aged 2 to 7 yr, Dmin-PO2 decreased significantly from 12.2 +/- 2.1 to 3.1 +/- 0.8 units, but after age 8 yr the values gradually increased from 3.1 +/- 0.7 to 6.4 +/- 1.6 units. In children aged 6 to 13 yr, Dmin-Rr showed the same increase as Dmin-PO2, from 2.0 +/- 0.5 to 5.8 +/- 1.4 units. These age-related changes in BRm reflected in both Dmin-PO2 and Dmin-Rr were also seen in the age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated inhalation challenge with exogenous and endogenous histamine released by acetaldehyde inhalation in asthmatic patients.

We previously reported that inhaled acetaldehyde, a metabolite of ethanol and a main factor in alcohol-induced asthma, causes bronchoconstriction indirectly through endogenously released histamine in asthmatic subjects. No study has examined the difference between tachyphylaxis in response to endogenous as opposed to exogenous histamine. Therefore, we examined tachyphylaxis occurring in response to repeated inhalation of histamine or acetaldehyde in nine asthmatic subjects. The mean acetaldehyde concentration causing a 20% decrease in FEV1 increased significantly from 18.4 (geometric standard error of the mean (GSEM = 0.14) to 45.2 (GSEM = 0.14) mg/ml over a period of 1 h (p < 0.002), whereas the mean histamine concentrations causing a 20% decrease in FEV1 were identical. No correlations were observed between the change in bronchial responsiveness to each solution and the change in baseline FEV1. These results suggest that tachyphylaxis in response to histamine is observed only when the latter is released endogenously. We believe that this is the first report suggesting tachyphylaxis caused by endogenous histamine.

The influence of training intensity, airway infections and environmental conditions on seasonal variations in bronchial responsiveness in cross-country skiers.

The influence of physical training, airway infections and environmental conditions on changes in bronchial responsiveness to methacholine during a training and competitive season was studied in 19 high-performance male cross-country skiers 19-21 years old. The longitudinal changes in the methacholine concentration required for a 10% fall in FEV1 (PC10) were negatively correlated with the changes in the volume of physical activity at an intensity level above 90% of maximal heart rate. The variation in physical activity at this intensity level accounted for 54.8% of the change in PC10. No association was found, however, with regard to physical activity at lower intensity levels. Seasonal variation in PC10 was not associated with the changes in occurrence or duration of airway infections provided that the PC10 measurement was postponed for 3-6 weeks after the onset of a recent infection. Seasonal variation in PC10 seemed not to be associated with variations in ambient levels of air pollutants or aeroallergens. PC10 was lowest at the end of the coldest part of the year. In conclusion, seasonal variation in bronchial responsiveness in high-performance cross-country skiers could to a great extent be explained by changes in the volume of physical activity at a very high intensity level.

Changes in bronchial responsiveness, circulating leucocytes and ex vivo cytokine production by blood monocytes after PAF inhalation in allergic asthmatics

We investigated the effects of inhaled platelet-activating factor (PAF) on methacholine bronchial responsiveness, circulating leucocyte counts, and ex vivo tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) production from blood monocytes in eight allergic asthmatics. Bronchial responsiveness was defined as the provocative concentration of methacholine causing a 20% decrease in forced expiratory volume in one second (PC20). Circulating leucocytes were counted by means of an automatic haemocytometer, and cytokines were measured with specific immunoassays. The different variables were measured before and 4, 24, 48, 72 and 168 h after a PAF (225 micrograms), a lyso-PAF (225 micrograms) and a saline bronchial challenge. When compared with lyso-PAF and saline, inhalation of PAF resulted in a significant decrease in PC20 over a period of one week. Two falls in bronchial responsiveness were identified, the first by 4 h and the second beginning 48 h and reaching a maximum by 168 h. The increases in spontaneous TNF alpha and IL-1 production which occurred during the week after both PAF, lyso-PAF and saline, did not differ significantly. Likewise, the changes in circulating neutrophil counts, characterized by a transient rise by 4 h after PAF and lyso-PAF but not saline, followed by a fall by 24 h and a persistent decrease until 168 h, were not significantly different after PAF, lyso-PAF and saline. On the other hand, in comparison with lyso-PAF and saline, inhaled PAF caused a significant protracted augmentation in circulating eosinophil counts, which was maximal by 48 h but did not correlate with the delayed decline in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring changes in logarithmic data, with special reference to bronchial responsiveness

Bronchial provocation tests with agents such as histamine and methacholine are commonly used in clinical and epidemiological studies of respiratory illness because bronchial hyperresponsivenes is a non-specific abnormality of the airways which is characteristic of asthma. However, measurements of bronchial responsiveness are log-normally distributed. As a result, special considerations need to be given to reporting within-subject changes in these measurements in longitudinal studies as, for example, in clinical trials or in any study in which a before-and-after experimental design is used. In these types of experiments, changes in bronchial responsiveness should not be simply expressed in the units of the measurement, such as dose of provoking agent, but must be expressed in units based on a logarithmic scale. The appropriate log-based units for measuring within-subject changes are doubling dose, fold difference or percent change. This paper explains the methods for calculating changes in these units in a statistically correct manner. All three units represent different ways of expressing the same change on a logarithmic scale. However, ‘doubling dose’ is only appropriate when it relates directly to the method of administering the provoking agent in doubling concentrations and ‘fold difference’ or ‘percent change’ are both appropriate for expressing any log-based changes. The methods for calculating changes in these units also apply to calculations of repeatability within test methods and to calculations of comparability and agreement between test methods. The methods are described solely for reporting changes in units of bronchial responsiveness but are applicable to other log-normally distributed measurements.