Assessment Of Bronchial Responsiveness Research Articles

The safety and feasibility of the inhaled mannitol challenge test in young children

To the Editor : The mannitol challenge is an indirect challenge that increases airway surface liquid osmolality resulting in bronchoconstriction [1, 2]. Mannitol challenge tests are used clinically to diagnose asthma and, in particular, exercise-induced broncoconstriction (EIB) in adults and children above 6 years of age [3]. To date, mannitol has not been used as a challenge agent in children under 6 years of age and the feasibility and safety of its use in this age group is unknown. The assessment of bronchial responsiveness in young children is difficult and limited by the cooperation of the child. The standardisation of lung function tests suitable for use in young children, such as the interrupter technique or the forced oscillation technique (FOT), provide an opportunity to assist in the assessment of bronchial responsiveness in young children and a variety of challenge tests using FOT have been reported in young children [4]. The aim of this preliminary study was to assess the feasibility and safety of the mannitol challenge test in young children using the FOT as the objective outcome measure. 20 children aged 3–7 years were recruited; 10 of these children were healthy and 10 children had a history of parentally reported exercise-induced symptoms (EIS) in the past year. The mannitol challenge test (Aridol; Pharmaxis, Frenchs Forest, Australia) was performed as previously published [2], with the exceptions that the respiratory resistance at 8 Hz ( R rs8) from the FOT was used as the primary outcome and the definition of a positive response was altered, as detailed below. Prior to …

Assessment of bronchial responsiveness on exposure to isometric exercise during different phases of menstrual cycle: A pilot study

The present study was planned to assess the effects of gonadal steroids (estrogen and progesterone) on bronchial responsiveness, before and after handgrip exercise, during different phases of menstrual cycle. In this study, 30 healthy (25-40 years), non-athletic, adult female volunteers were studied. The various pulmonary function parameters (FVC, FEV1, PEFR, FEF 25-75%) were recorded with a spirometer under resting conditions and then within five minutes of cessation of isometric exercise. Recordings were taken during the Menstrual phase (MP), Proliferative phase (PP), and Luteal phase (LP) of menstrual cycle and were confirmed by plasma levels of estrogen and progesterone. The oral temperature was recorded during each phase of the menstrual cycle. Under resting conditions, the above-mentioned parameters did not reveal significant differences during the three phases. A significant fall was observed only in the Peak Expiratory Flow Rate (PEFR) during all the phases after handgrip, but there was a non-significant decline in the other parameters. By this study we conclude that the physiological changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway responsiveness before and after the handgrip test. The general fall seen in the pulmonary parameters could be due to fatigue or psychic factors.

SPUTUM EOSINOPHIL COUNT IN ATHLETES WITH ANTIASTHMATIC THERAPEUTIC USE EXEMPTION

Dear Editor-in-Chief: The prevalence of asthma has increased steadily in recent years, and it is surprisingly high in athletes (1,2,4). Although several drugs are banned in competitive sports, antiasthmatics such as beta-agonists and corticosteroids are legally admitted when administrated by metered-dose inhaler in the treatment of asthma. However, a variety of beta-adrenergic drugs, particularly clenbuterol, when administered orally or parenterally, develops an illicit activity on the myosin fibers and on the muscles (2). Accordingly, clear rules must be stated to set or verify a diagnosis of asthma in athletes to prevent cheating and harm during competition (1,2,4). Declared medications are commonplace in sports, embracing a wide series of drugs (6). However, the extraordinary number of therapeutic use exemption for antiasthmatics in sportsmen (2,4) calls for the implementation of enhanced thresholds. The diagnosis of asthma is mainly based on history of symptoms, physical examination of signs indicating the presence of bronchial obstruction, and variability in lung function spontaneously or due to bronchodilators (1). Hull et al. (4) recently highlighted that the diagnosis of asthma in athletes is particularly important because of potential implications on performance and strict regulations concerning the use of medications. Accordingly, when an athlete participates in international sports, the Joint Task Force of the European Respiratory Society and the European Academy of Allergy and Clinical Immunology recommend that a combination of medical history and laboratory tests should be documented as basis for the diagnosis of asthma and the possibility to use medications (1). Functional tests include lung function, in particular, maximum expiratory flow volume loops, with the assessment of reversibility to an inhaled beta-2 agonist such as salbutamol and the assessment of bronchial responsiveness either by a direct or by an indirect method (1). However, the use of these tests has some caveats because neither are they usually performed under direct jurisdiction of a sport medical commission nor can they be easily repeated on all athletes competing in the athletic field. Therefore, an alternative, cost-effective screening strategy should be designed (4) to verify whether therapeutic use exemptions are clinically motivated. Sputum analysis for evaluating the percentage of eosinophilia directly measures airway inflammation and objectively monitors asthma (5). Induced sputum eosinophil count was proven sensitive (90%) and specific (92%) in patients with bronchial asthma compared to subjects with asthmalike symptoms, all asthma patients presenting with eosinophil count >1% (3). At variance with blood testing, which requires a venipuncture and a dedicated apparatus for collection and handling, sputum is easily collected by noninvasive means. Moreover, eosinophil count is affordable at reasonable costs because it is routinely performed in clinical laboratories and can also be transferred to the athletic field using a common hematological analyzer. Indeed, eosinophil count in the induced sputum is not intended to replace a diagnosis on the basis of clinical signs and functional tests, but it may be a reliable and an inexpensive screening to preliminarily identify those athletes who are unlikely to suffer from asthma.

Assessment of bronchial responsiveness in preschool children

Preschool children have a short concentration span and relatively poor cooperation with pulmonary function tests (PFTs). This combination complicates the inhalation protocol and the assessment of bronchodilation/bronchoconstriction in this age group. Bronchial responsiveness can be studied after bronchodilator administration or during bronchial challenge using miscellaneous PFTs. This article enclosed information on when to consider significant a PFT change, and published proposed cutoffs for bronchodilation/bronchoconstriction test. Issues on interpretation of bronchial test are also discussed. Recommendations are provided on behalf of the Interrupter Technique Subcommittee of the ATS/ERS Working Group on Infant and Young Children Pulmonary Function Testing.

Use of interrupter technique in assessment of bronchial responsiveness in normal subjects

BackgroundA number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD20 FEV1.MethodsWe studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD100Rint, EI) as well as by percent dose response ratio (DRR).ResultsBHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD20FEV1 (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV1 in terms of reactivity (DRR).ConclusionsInterrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.

Assessment of Bronchial Responsiveness Following Exposure to Inhaled Occupational and Environmental Agents

Inhalation of a range of agents can result in airway inflammation and/or irritation. This may result in occupational asthma or reactive airways dysfunction syndrome. Reactive airways dysfunction syndrome follows a single large exposure to a chemical agent but is now frequently embraced under the wider term of irritant-induced asthma, a term that also includes asthma due to persistent, lower dose irritant exposures. Bronchial hyperresponsiveness is a hallmark of both occupational asthma and reactive airways dysfunction syndrome, although some patients with occupational asthma may occasionally have typical clinical features without increased bronchial hyperresponsiveness. Following removal of the causal agent in occupational asthma, bronchial hyperresponsiveness generally returns towards normal over a 2-year period, although some individuals demonstrate increased bronchial hyperresponsiveness for longer. Measurement of specific bronchial hyperresponsiveness to the primary causal agent in occupational asthma is used diagnostically but not for assessing prognosis. Bronchial hyperresponsiveness to inhaled methacholine can be measured across individual workshifts to assess work-related change. It may also be measured at the end of a work period when exposure has occurred, and compared with values following a period away from work. There have been no direct, systematic comparisons of changes in methacholine responsiveness in the diagnosis of occupational asthma compared with the more frequently used serial peak flow measurements. Patients with reactive airways dysfunction syndrome classically exhibit non-specific bronchial hyperresponsiveness, which can be readily measured by evaluating responses to inhaled methacholine. Bronchial hyperresponsiveness in reactive airways dysfunction syndrome can persist for many years after initial exposure and serial changes can be used to assess recovery and subsequent disability over time.

Efecto del débito de nebulizadores tipo jet sobre el valor de la PC20 en niños asmáticos

This study aimed to assess the effects of two different nebulizer outputs on airway responsiveness to methacholine in asthmatic children. Twenty-seven atopic asthmatic children aged 6 to 14 years inhaled methacholine according to the Cockroft method until FEV1% had decreased 20% with respect to saline inhalation (PC20). The bronchial challenge tests were performed using two different types of jet nebulizer: Ava Neb 1780 and Hudson UP Draft II 1730, the outputs of which were 205 +/- 13 mg/min and 356 +/- 31 mg/min, respectively (p < 0.05). For 9 out of 27 patients (33%) the PC20 values were significantly different (one or more double concentrations) for the two nebulizers. However, 7 of those 9 children showed significantly lower bronchial responsiveness when the challenge tests were conducted with the low output jet nebulizer. This study suggests that using jet nebulizers with different outputs can markedly influence the results of methacholine challenge tests in asthmatic children. Such an influence could introduce significant bias in the assessment of bronchial responsiveness in comparative measurements in a single individual or in populations.

Bronchial hyperresponsiveness and airway wall remodelling induced by exposure to allergen for 9 weeks.

Prolonged exposure to allergen has been proposed to be important for the development of bronchial hyperresponsiveness and airway remodelling in asthma. The present study was designed to examine the effect of chronic allergen exposure on bronchial responsiveness, eosinophil infiltration, and airway remodelling. We sensitized brown Norway rats with the occupational allergen trimellitic anhydride (TMA) and exposed the animals to TMA conjugated to rat serum albumin (TMA-RSA) on 5 consecutive days each week for 9 weeks, starting 4 weeks after sensitization. IgE and IgG anti-TMA antibodies in serum and bronchial responsiveness to acetylcholine were evaluated before and at weeks 3, 6, and 9 of allergen exposure. Thickness of the airway wall, airway luminal narrowing, and the number of goblet cells and eosinophils in the airway wall were evaluated with an image analysis system in lungs resected after the last assessment of bronchial responsiveness, at the end of the 9-week allergen exposure. All rats developed IgE and IgG anti-TMA antibodies after sensitization. The levels of antibodies increased with allergen exposure until week 6, and then declined. Bronchial hyperresponsiveness to acetylcholine was induced in allergen-exposed rats without ongoing airway eosinophilia. Bronchial hyperresponsiveness induced by chronic allergen exposure via inhalation was accompanied by significantly increased thickness of smooth muscle and airway narrowing in the small airways, and goblet cell hyperplasia in the large airways. We conclude that chronic exposure to allergen can induce bronchial hyperresponsiveness and airway wall remodelling. Airway wall remodelling may contribute to bronchial hyperresponsiveness.

Simple forced oscillatory technique and spirometry in assessment of bronchial responsiveness in non‐asthmatic and asthmatic subjects

Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow-volume spirometry in detection of bronchial changes during induced bronchoconstriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non-asthmatic subjects (n = 61) of which 44 were classified as responders (delta FEV1 > or = 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (delta max/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose-response curves were similar for all parameters. In the non-asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60-Rrsfo versus PC10-FEV1, P < 0.05; PC60-Rrsfo versus PC25-MMEF, P < 0.01). In the non-asthmatic responsive subjects, the correlations between PC60-Rrsfo and PC25-MMEF were significant (P < 0.05). Thus, Rrsfo at a fixed 8 Hz frequency and built-in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non-asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.

Effect of the selective thromboxane A 2 receptor antagonist, S-1452, on antigen-induced sustained bronchial hyperresponsiveness

Long-lasting bronchial hyperresponsiveness to i.v. acetylcholine was observed in actively sensitized guinea-pigs after aerosol ovalbium exposure. The response became significant at 7 h post-challenge and persisted for at least 120 h compared to the response of unsensitized animals. Pretreatment of animals with the specific thromboxane A 2 receptor antagonist, S-1452 (calcium (1 R, 2 S, 3 S, 4 S)-(5 Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1]hept-2-yl) hept-5-enoate dihydrate), almost completely inhibited the onset of bronchial hyperresponsiveness, as assessed at 24 and 120 h post-challenge. However, it was ineffective when administered at 1 h post-challenge or 2 h before assessment of bronchial responsiveness. Lung vascular injury occured transiently immediately after antigen challenge, the kinetics of injury being associated with those for the production of thromboxane B 2 in bronchoalveolar lavage fluid. The vascular injury was dramatically suppressed by pretreatment with S-1452. These findings suggest that acutely generated thromboxane A 2 plays an important role in the pathogenesis of antigen-induced long-lasting bronchial hyperresponsiveness, probably by producing vascular damage in the lungs.

Measurement of bronchial responsiveness by forced oscillation technique in occupational epidemiology

The performance of the forced oscillation technique (FOT) in the assessment of bronchial responsiveness on the methacholine challenge test was compared with that of forced expiratory volume in one second (FEV1) in 119 active workers with normal baseline pulmonary function. Changes in resistance (delta R0%), frequency dependence of resistance (delta P) and resonant frequency (delta F%) determined by the FOT were compared to the delta FEV1%. Receiver operating characteristic (ROC) curves were established to determine values of the changes in FOT parameters which corresponded to the best sensitivity and specificity for classifying the subjects as hyperresponsive or nonresponsive on the methacholine challenge test. Significant correlations were observed between delta FEV1% and delta R0%, delta P and delta F% respectively. The ROC curves showed the following cut-off values of FOT parameters to be the best values for classifying the subjects according to the presence or absence of 20% fall in FEV1: a 65% increase in R0 (sensitivity 75%; specificity: 76%); a decrease of 65 x 10(-3) hPa.l-1.s2 in P (sensitivity 58%; specificity 83%); a 50% increase in F (sensitivity 75%; specificity 62%). Our results suggest that the FOT is a useful test for assessment of bronchial hyperresponsiveness when compared to spirometry, and can be applied to epidemiological studies of a bronchial challenge test in normal active working populations.

Acoustic vs. spirometric assessment of bronchial responsiveness to methacholine in children.

To study wheezing as an indicator of bronchial responsiveness during methacholine challenge (MC) in children, we used computer analysis of respiratory sounds and compared wheeze measurements to routine spirometry. MC was performed in 30 symptomatic subjects (sympt), age 11 +/- 3.1 years (mean +/- SD), with suspected asthma and in 12 controls (contr), age 10 +/- 3.4 years. Respiratory rate (RR), spirometry, arterial oxygen saturation (SaO2), and cough were registered until the concentration provoking a > or = 20% fall in forced expiratory flow in 1 second (FEV1;PC20), or the end point (8 mg/mL) was reached. For 1 min after each inhalation, sounds over the trachea and posterior right lower lobe were recorded together with calibrated airflow. Computer analysis of respiratory sounds was used for objective wheeze quantification. Wheezing was measured as its duration relative to inspiration (Tw/Ti) and expiration (Tw/Te). Seventeen of the sympt group developed wheezing (sympt/W) with > or = 5% Tw/Ti or > or = 5% Tw/Te. Thirteen of the sympt did not wheeze (sympt/no W). Three contr developed wheeze (contr/W) while 9 did not (contr/no W). In sympt/W, RR increased from 20 +/- 6.2 per min at baseline to 25 +/- 9.2 (P < 0.05) at the MC concentration provoking wheeze (PCw), and SaO2 decreased from 97.4 +/- 1.2% to 95.3 +/- 2.4 (P < 0.05). In contr/W, RR did not change, but SaO2 decreased from 97.3 +/- 1.5% to 95.7% +/- 1.2% (P < 0.05). Wheezing occurred at both recording sites and was as common during inspiration as during expiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Bronchial Responsiveness as a Guide to Prognosis and Therapy in Asthma

The severity of airway inflammation in patients with asthma is best assessed by combining several tests of bronchial responsiveness. The prognostic significance of bronchial responsiveness is unknown, but indirect evidence suggests that those with moderate and severe asthma rarely remit spontaneously and permanently. Assessment of severity is crucial to the rational management of all patients with asthma. Severity can be used as a guide to both short- and long-term management.