Degree Of Bronchial Responsiveness Research Articles

Limited airway effects in mild asthmatics after exposure to air pollution in a road tunnel

Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum. Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected. The median PM(2.5) and PM(10) levels during the exposure occasions in the road tunnel were 80 (range 41-93) μg/m(3) and 183 (72-213) μg/m(3) respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1s (FEV(1)) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure. We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants.

Use of inhalation corticosteroids (ICS) in children with asthma in general practice

Background:To prevent airway remodelling and the development of irreversible airway obstruction, inhaled corticosteroids (ICS) should be introduced in an early phase of the disease. Dutch guidelines recommend ICS for children with moderate to severe asthma.Aim of the study:To evaluate the use of ICS in relation to the severity of asthma.Methods:We evaluated asthma symptoms during 2 weeks, bronchial hyper-responsiveness (BHR), and the use of ICS in 74 children (age: 7–16) who were previously prescribed anti asthma medication in general practice. BHR was measured by using a Methacholine inhalation challenge test. Doubling doses of methacholine, beginning with 0.03 mg to a maximum of 1.8 mg (cumulated dose max. 3.6 mg), were administered with the Jeager Masterscope, Aerosol Provocation System (APS), medic aid side stream nebulizer. The degree of bronchial responsiveness was expressed as a PD20, a provocation dose that induces a 20% fall in FEV1 from baseline.Results:Thirty-eight children (51%) reported asthma symptoms on four or more days in their 2 weekly diary. Twenty-seven of these children (71%) had moderate to severe BHR (PD20 <300:g). Two of these children did not use ICS at all, fourteen used ICS intermittent, only eleven used ICS as a maintenance therapy.Conclusion:Our data indicate undertreatment of asthma in children. Health care providers, patients and parents should be more aware of the importance of maintenance therapy of ICS. There seems to be considerable room for improvement.

The prevalence and severity of bronchial hyper-responsiveness (BHR) in asthmatic children in general practice

The degree of BHR, in relation with the presence of symptoms, is generally accepted as an estimate of asthma severity. The majority of asthmatic children is treated in general practice while measurement of BHR is not being used. To assess the prevalence and severity of BHR in children with asthma in general practice. 800 Children treated in general practice who used asthma medication in the previous year were asked to participate. BHR was evaluated in 373 of these possible asthmatic children (age: 7–16) by a methacholine challenge test. The degree of bronchial responsiveness was expressed as PD20. 277 (74%) of all participating children were hyperresponsive according to the PD20: 55 (20%) severe (PD20 < 0.075 mg), 101 (36%) moderate (PD20 0.075–0.30 mg), 63 (23%) mild (PD20 0.30-1.0 mg) and 58 (21%) borderline (PD20 1.0–4.0 mg). In 13 (3.5%) the inhalation challenge was not started because of a FEV1 < 75% of predicted. 72 children did not demonstrate BHR. In 11 children performance of lungfunction was technically inadequate. Two-fifth of children treated in general practice with asthma medication demonstrate moderate to severe BHR and sometimes even severe airflow obstruction. These data could be an indication that asthmatic children are not using appropriate medication.

Validation of a single concentration inhalation provocation test (SCIPT) in children

Background:A new method to assess bronchial responsiveness (BR) using a single concentration methacholine has already been validated in adults with asthma1. Since the geometrical dimensions of the airways in children are different, and deposition of the inhaled aerosol also differs in children, results from studies in adults cannot simply be extrapolated to children.Aim of the study:validation of a single-concentration inhalation provocation method in children.Methods:Twenty-three subjects performed three methacholine inhalation challenge tests. The first two challenges according to method A: doubling doses, beginning with 0.03 mg to a maximum of 1.8 mg (maximal cumulated dose 3.6 mg), were administered with the Jeager Masterscope, Aerosol Provocation System (APS), medic aid sidestream nebulizer. The third challenge according method B: doubling doses, beginning with 0.002mg to a maximum of 1.8mg (maximal cumulated dose 3.5 mg), were administered with a Devillbiss 646 nebulizer. The degree of BR is expressed as a PD20. A difference of <1,5 dose step is assumed to be due to intra individual variation.Results:I.C.C. between method A and B is 0.80 and between both tests according method A 0.91. Comparing challenges 1 and 2, and 1 and 3 showed good agreement according to Bland and Altman.2Conclusion:This single concentration method is an accurate method of measuring BR in children.

Bronchial hyperresponsiveness in adults with seasonal and perennial rhinitis: is there a link for asthma and rhinitis?

Epidemiological studies have shown that asthma and rhinitis often coexist in the same patients and the prevalence of asthma is greater in patients with rhinitis. The aim of this study was to evaluate the differences in bronchial reactivity in subjects with seasonal and perennial rhinitis. We enrolled 128 subjects with seasonal or perennial allergic rhinitis divided into three groups: A with perennial rhinitis and allergy to Dermatophagoides Pteronissynus; B with seasonal rhinitis and allergy to Graminae and Parietaria, who underwent methacholine challenge test (MCHt) during the exposure period (fron March until May); C with seasonal rhinitis and allergy to Graminae and Parietaria, who underwent MCHt during the non exposure period (from June until February). The PC20 mean values of group A (1774.8 &#x00B1; 20.7) and group B (1740.7 &#x00B1; 38.8) were not significantly different, but significantly lower than those of group C (3010.0 &#x00B1; 56.9) (p=0.001). The subjects with group A were positive to the MCHt in 54.54&#x0025;, against 29.28&#x0025; of group B and 11.62&#x0025; of group C (p=0.007). The results show differences in the degree of bronchial responsiveness. The dose-response curves documented a lower value of PC20 in the group with perennial rhinitis and a statistically significant difference of bronchial hyperresponsiveness prevalence between the three groups (p=0.007).

Thrombin in the airways of asthmatic patients.

The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that, in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor were measured in the sputum of all subjects. The concentrations of thrombin (p = 0. 007), TAT (p = 0.01), and tissue factor (p = 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that sputum from asthmatic patients (p = 0. 01) and thrombin (p = 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the sputum concentrations of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether these findings are also observed in other airway diseases.

Serum house dust mite antibodies: predictor of increased bronchial responsiveness in adults of a community.

The purpose of this study was to determine whether the presence of serum specific immunoglobulin E (IgE) antibodies was associated with increased bronchial responsiveness in adults. We studied cross-sectionally a random community sample of 18-73 year old adults, of whom 83% (n = 489) performed bronchial responsiveness testing as well as serum measurements of five specific IgE antibodies. In the crude data, 39% of those with house dust mite antibodies (n = 18) had a bronchial responsiveness < or = 32 g.L-1 methacholine compared with 19% in subjects without any of the five specific IgE antibodies (n = 453). The corresponding percentages for subjects with timothy antibodies (n = 16) was 25%, birch antibodies (n = 13) 23%, cat antibodies (n = 10) 40% and mould antibodies (n = 2) 50%. When assessing the multivariate relationship between the presence of one specific IgE antibody and degree of bronchial responsiveness we used a semi-proportional hazards model with the response as a 20% fall in forced expiratory volume in one second (FEV1) from pretest value. Covariates included in the model were: gender, age, pretest FEV1, smoking habits, pack-years, season and other specific IgE antibodies than that examined. The presence of house dust mite antibodies was a significant predictor (p < 0.01) of increased bronchial responsiveness in never- and ex-smokers. Indoor allergic sensitization (house dust mite, cat and mould) was a significant predictor of increased bronchial responsiveness, while outdoor allergic sensitization (timothy and birch) was not. Excluding subjects with obstructive lung disease (n = 39) or including the covariate log total serum IgE as a potential confounder yielded the same result. Thus, in this community, indoor allergic sensitization rather than allergic sensitization per se was related to increased bronchial responsiveness after adjusting for other relevant covariates.

FOLLOW-UP OF ASTHMA FROM CHILDHOOD TO ADULTHOOD: INFLUENCE OF POTENTIAL CHILDHOOD RISK FACTORS ON THE OUTCOME OF PULMONARY FUNCTION AND BRONCHIAL RESPONSIVENESS IN ADULTHOOD

FEV1 in adults with asthma was significantly predicted only by the childhood level of FEV1. The presence of bronchial responsiveness in adulthood was significantly predicted by the female gender and the degree of bronchial responsiveness in childhood. The degree of bronchial responsiveness in adulthood was only weakly related to the initial degree of responsiveness in childhood.

Bronchial Responsiveness in Children and Adolescents: A Comparison Between Previously Asthmatic, Currently Asthmatic, and Normal Subjects

The aim of this study was to examine the degree of bronchial responsiveness in previously asthmatic subjects. Of 253 patients, born within 1964-1974, followed in the pediatric department at the University hospital in Copenhagen, 224 subjects (89%) were successfully contacted by telephone; of these 195 complained of persistent asthma and 29 (13%) had had no asthmatic symptoms for at least 2 years. On the basis of the degree of respiratory symptoms, 58 individuals were examined at the outpatient clinic. Of these, (1) 19 were previously asthmatics, (2) 20 had current mild asthma, and (3) 19 had current severe asthma. Furthermore, 19 healthy individuals, age-matched with the preceding asthmatic subjects, were selected as controls. In all subjects, skin prick tests, lung function tests, and bronchial challenge tests with inhaled histamine and bronchodilator were performed. Furthermore, the subjects measured their peak expiratory flow (PEF) twice daily during a period of 4 weeks. Of the 39 current asthmatic subjects, 82% had a PC20 < or = 8 mg/ml, whereas all previously asthmatic subjects and the controls had a PC20 > 8 mg/ml. The degree of bronchial responsiveness as indicated by the dose-response slope (DRS), the percentage change in forced expiratory volume in 1 sec (FEV1) per inhaled mumol of histamine, was found to be significantly higher in previously asthmatic patients (median logDRS 0.1 delta %FEV1/mumol) than in controls (median logDRS-0.4 delta %FEV1/mumol) (p < 0.001). Furthermore previously asthmatic subjects had significantly increased change in FEV1 after inhalation of bronchodilator and peak expiratory flow variability compared to controls. These findings suggest that apparently asymptomatic previously asthmatic subjects have increased airway variability.

Effect of alterations of dietary sodium on the severity of asthma in men.

There is some evidence of a positive association between increased dietary salt consumption and both increased bronchial reactivity and mortality from asthma in men. This study assesses the effects of alterations in dietary salt consumption on the clinical severity of asthma in adult male asthmatic patients. A randomised, double blind, placebo controlled, crossover design was employed. Twenty seven mild to moderate asthmatic patients were established on a low sodium diet (80 mmol/day) at the end of a 4-5 day run in period and then randomised to receive 200 mmol/day slow sodium or matching placebo for five weeks, crossing over to the alternative regime for a further five weeks. Patients used diary cards to record twice daily peak expiratory flow rates, daily symptom scores, and bronchodilator consumption. Spirometry and degree of bronchial responsiveness (methacholine challenge test) were measured at screening and at the end of each treatment period. Twenty four hour urinary sodium excretion was measured at screening and in duplicate for each treatment period. Twenty two patients completed the study. For these patients the mean (95% confidence interval (CI)) difference in 24 hour sodium excretion between treatments was 204 (175 to 235) mmol. Compared with placebo, sodium supplementation resulted in deleterious alterations of all measured parameters. Bronchial reactivity rose on slow sodium with a 0.73 (0.2 to 1.3) doubling dose methacholine difference compared with placebo. Estimated median (95% CI) difference in bronchodilator consumption was 1.3 (0.4 to 2.1) puffs per day, the estimated median difference in symptom score was 0.6 (0.2 to 0.9), and mean forced expiratory volume in one second fell by 0.21 (0.05 to 0.37) 1. The peak expiratory flow rate rose on placebo and fell on slow sodium. Median differences between treatments were 5.6% (2.2% to 9.8%) for morning and 7.8% (3.9% to 12.9%) for evening peak expiratory flow rate. Our results suggest that large increases in dietary sodium result in physiological deterioration and increased morbidity in male asthmatic patients.

Relationship between viral antibodies and bronchial hyperresponsiveness in 495 unselected children and adolescents

The purpose of this study was to investigate whether recent and previous subclinical viral respiratory infection can explain the presence of increased bronchial responsiveness to histamine. We studied a randomly selected population of 495 children and adolescents, aged 7-16 years, from Copenhagen. If the subjects had had symptoms of respiratory infection recently, the examination was postponed for at least 6 weeks. Bronchial hyperresponsiveness (BHR) to inhaled histamine was found in 79 (16%) of the subjects, of whom 28 had asthma. Forty-eight subjects (10%) had increased levels of serum IgM antibodies against either parainfluenza, influenza, adenovirus, or respiratory syncytial virus (RSV), reflecting a recently acquired infection. No association between BHR and antibodies against respiratory viruses was found, as 7 (8.9%) of the 79 subjects with BHR and 41 (9.9%) of the 416 subjects without BHR had viral antibodies. Furthermore, no association between degree of bronchial responsiveness and viral antibodies was found. Moreover, 251 individuals (51%) had signs of earlier RSV infection, i.e. IgG antibodies against RSV. No relationship was found between age of the subjects and the presence of antibodies against either respiratory viruses in general or IgG-RSV. No relationship was found between the presence of antibodies against RSV and BHR; furthermore, evidence of earlier RSV infection was unrelated to the level of lung function and degree of bronchial responsiveness. We conclude that increased bronchial responsiveness in asymptomatic, unselected schoolchildren and adolescents is not likely to be caused by recent or previous viral respiratory infections.

Distribution of radioactive aerosol in the airways of children and adolescents with bronchial hyper-responsiveness.

The purpose of this study was to examine the relationship between the pulmonary distribution of inhaled radioaerosol, bronchial responsiveness, and lung function in children and adolescents. The participating subjects (n = 39) were divided into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR), (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR. Pulmonary distribution of [99Tcm) albumin radioaerosol, maximal expiratory flow when 25% of forced vital capacity remain to be exhaled (MEF25), and bronchial responsiveness to inhaled histamine were measured. Twenty subjects (52%) had irregular central distribution and 19 subjects (48%) had regular distribution of radioaerosol in their lungs. No difference in distribution of radioaerosol was found between the three groups of children. The median MEF25 among non-asthmatic subjects (80% predicted) was lower than that found in controls (92% predicted) but higher than that found in asthmatic subjects (55% predicted). A relationship was found between reduced flow at the peripheral airways, as indicated by MEF25 and the degree of central distribution of radioaerosol. Furthermore, subjects with irregular central distribution of radioaerosol had an increased degree of bronchial responsiveness. In conclusion, children and adolescents who have flow rates in the peripheral airways or increased degree of bronchial responsiveness tend to have abnormal distribution of radioaerosols.

Development of Lung Function in Relation to Increased Degree of Bronchial Responsiveness

To study the relationship between development of lung function and bronchial responsiveness, we examined 106 subjects recruited from a random sample of 527 subjects, aged 8-18 years, from Copenhagen. Lung function and bronchial responsiveness to inhaled histamine were measured at two occasions, in 1986 and 1988. The participating subjects (n = 106) were divided into three groups: (a) 20 asthmatics with bronchial hyperresponsiveness (BHR), (b) 42 nonasthmatic subjects with BHR in 1986, and (c) 44 controls without BHR. In 1986, FEV1 expressed as percentage of predicted value, was found to be similar in the three groups (91%, 94%, and 99%, respectively). The increase in height during the observation period was found to be 5, 6, and 6 cm, respectively, in the three groups. However, at the second examination, in 1988, FEV1 was found to be significantly reduced in both asthmatics (87%) and nonasthmatic subjects (85%) compared with the controls (103%). In 1988, 16 asthmatics (80%) and 24 (57%) nonasthmatic subjects were found to have BHR, whereas none of the controls were found to have BHR. A multiple regression analysis was used to determine the correlation between change in FEV1 and potential factors of importance. The change in FEV1 was highly correlated with the presence of BHR in 1986, however, no correlation was found between change in FEV1 and change in bronchial responsiveness. In conclusion, nonasthmatic subjects with former BHR showed signs of airflow obstruction and less increase in lung function during growth irrespective of the change in level of bronchial responsiveness, which may suggest a risk for subsequent development of obstructive lung disease.

Passive smoking in childhood—Tobacco smoke

Prevalence of cigarette smoking varies widely in different countries, ranging, at the age of 13, from 2% to 5% (Sweden, United States) to more than 30% (Australia, Uruguay). Even if the prevalence of smokers among male adolescents is decreasing in western countries, it is increasing among girls and, in developing countries, male adolescent smokers still reach 40% (and up to 70%-80%). The determination of saliva cotinine levels, a product of nicotine metabolism, is an useful indicator of exposure to passive or active smoking. In a study of 210 children aged 9-13 years, we found detectable levels of saliva cotinine in 13% of children who lived in nonsmoking families and denied being regular smokers and in only 60% of children living in families with heavy cigarette consumption. This wide variations of a marker of smoking exposure may explain the differences in reported consequences of tobacco smoke in investigations conducted in different places and on different target populations. We later studied the effects of environmental tobacco smoke (ETS) in a sample of 166 nine-year-old children. The relationship between parental smoking and degree of bronchial responsiveness in males was significant. Also, prick skin test reactivity to allergens was significantly increased in children of smoking parents. Many studies concerning the effects of ETS exposure seem to demonstrate that not only the lungs and not only children are affected even if the difficulty of the epidemiology in such a field must suggest caution in interpreting the results.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of airway responsiveness in smokers with chronic bronchitis and in asthmatic subjects

Fifty-two of 95 smokers with a forced expiratory volume in one second (FEV1) above 70% predicted and with chronic bronchitis were found to have increased bronchial responsiveness, expressed as PC20FEV1, upon challenge with inhaled histamine. The degree of responsiveness was significantly below that found in matched asthmatics, but substantially higher than that reported in normals. The degree of responsiveness was significantly correlated to prechallenge ventilatory capacity, age and tobacco consumption but not to sex. PC40MEF50 showed the same distribution as PC20FEV1, but did not add further information. The slope of the dose response curve expressing the maximum expiratory flow at 50% of vital capacity expired (MEF50) did not correlate with any of the parameters measured. The slope of the FEV1 dose-response curves showed significant correlation with tobacco consumption. The degree of bronchial responsiveness as an indication for future disability needs to be investigated.

Prevalence and predictors of bronchial hyperresponsiveness in children aged 7-16 years.

To study the prevalence and possible predictors of bronchial responsiveness we examined a cross-section of 527 children aged 7-16 years from Copenhagen. The method used included an interview with the child and the parents, skin prick test with common allergens and se-IgE. Bronchial responsiveness was measured by a histamine inhalation test. We found that 79 (16%) of the children had bronchial hyperresponsiveness (BH), defined as a 20% fall in FEV1 with a provoking concentration of histamine (PC20) at 8 mg/ml or less. Atopic symptoms defined as asthma, rhinitis or eczema were significantly (P less than 0.001) correlated to BH both in prevalence and degree of BH. None of the children with urticaria had BH. The degree of bronchial responsiveness was also significantly influenced (P less than 0.001) by family disposition to atopy, whereas we found no correlation between BH and "passive" smoking, specific skin test in unselected children, or elevation of IgE in children without atopic symptoms. We conclude that BH is severest in children with asthma, independent of elevated IgE or positive skin prick test. Children with rhinitis, dermatitis, or asymptomatic BH have the same degree of BH; this differed from that in children with asthma.

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.