Prostaglandin D2 potentiates airway responsiveness to histamine and methacholine

In the bronchi of asthmatic subjects many bronchoconstrictor mediators and neurotransmitters might be released together, and therefore, potential interactions might occur that could be important in airway hyperreactivity. We have studied the effect of inhaled methacholine, bradykinin, and prostaglandin D2 (PGD2) on bronchial reactivity to inhaled histamine in 6 mild asthmatic subjects, 22 to 36 yr of age. All of the test spasmogens were given at equivalent bronchoconstricting concentrations. Simultaneous dosing with PGD2 caused a significant increase in reactivity to histamine, mean dose of histamine causing a 35% fall in specific airway conductance being 0.72 mumol before, and 0.32 mumol with, PGD2; (p less than 0.01). This was not seen with histamine itself, methacholine, or bradykinin. Prostaglandin D2 caused a similar increase in bronchial reactivity to inhaled methacholine, suggesting a postreceptor potentiation of airway smooth muscle contractility. This positive interaction between inflammatory mediators known to be released in asthma has important implications for understanding bronchial hyperreactivity.     

Bronchial response to methacholine in parents of asthmatic children

Cumulative dose response curves to inhaled methacholine were established in 28 parents of asthmatic children, seven parents of healthy children, and four asthmatic patients. Bronchial sensitivity was defined as the dose of methacholine causing a 25 percent decrease in specific airway conductance while bronchial reactivity was determined by the slope of the cumulative dose response curve. Results indicated that parents with allergic rhinitis or airflow limitation in small airways may represent a high risk group, while parents with no atopy and normal pulmonary functions may reflect only the inherited characteristics of bronchial response.     

Airway hyperresponsiveness and pulmonary function in adult asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) is a very important factor in the pathogenesis of bronchial asthma. OBJECTIVES: To examine the relationship between airway obstruction and AHR in adult asthma. METHODS: This study was a retrospective study in 161 adult asthmatic patients. Nonspecific AHR to methacholine was measured. We examined the correlations between AHR and pulmonary function, severity of asthma, type of asthma and age. RESULTS: In the moderate and severe groups, peripheral airway obstruction was more aggravated compared to the mild group, and AHR was significantly more severe. Analysis of AHR by age showed that the degree of airway obstruction increased with aging, but age did not clearly correlate with airway sensitivity. Airway reactivity decreased with aging. Aspirin-induced asthma tended to be severe. In fatal asthma, central airway obstruction was significantly more severe. Although AHR in fatal asthma did not significantly differ from that in the severe group, airway sensitivity and airway reactivity tended to be increased. CONCLUSIONS: AHR is an important factor determining the severity of asthma, and airway obstruction is an important index for the prediction of death from asthma. An evaluation of the degree of AHR and airway obstruction is considered to be the first step in controlling asthma.     

Cold air as a bronchial provocation technique. Reproducibility and comparison with histamine and methacholine inhalation

Bronchial provocation testing with cold air was carried out on 36 asthmatic and 13 normal subjects in order to assess the reproducibility and clinical relevance of the technique as a test of airways reactivity. Sixteen subjects underwent repeat testing after an interval of two to three weeks. Using a least squares linear regression analysis, the technique was highly reproducible, with a correlation of r = 0.93 (p less than 0.001). The 21 asthmatic subjects who had exercise-provoked symptoms required a significantly lower level of ventilation of cold air to produce a 35 percent drop in specific airways conductance (PD35) than did those who had no exercise-induced asthma (33.9 L min-1 vs 45.8 L min-1; p less than 0.02). Subjects requiring no regular treatment for their asthma had a geometric mean PD35 of 62.6 L min-1, significantly higher than those requiring inhaled therapy (44.9 L min-1; p less than 0.005). Subjects requiring oral in addition to inhaled treatment had the lowest PD35 (23.6 L min-1; p less than 0.02). Atopic status did not appear to influence the response. There was a strong correlation between the PD35 to cold air and to histamine (r = 0.92; p less than 0.001) and between the PD35 to cold air and to methacholine (r = 0.86; p less than 0.001). The three techniques of assessing bronchial reactivity were equally successful in separating the normal and asthmatic groups. The results indicate that cold air provocation may be reliably and reproducibly used to assess bronchial reactivity. The use of a naturally-occurring stimulus of asthma in all subjects has great potential as an investigational technique.     

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children.

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.     

Effect of corticosteroids on bronchial responsiveness to methacholine in asthmatic children

To elucidate the effects of corticosteroids on nonspecific bronchial reactivity in asthmatic children, inhaled challenges with methacholine were conducted in 10 atopic asthmatic subjects (9 to 15 yr of age) before and after consecutive week-long trials of daily orally administered placebo and prednisone (60 mg/day). Pharmacologic bronchial sensitivity was evaluated as the log dose of methacholine producing a 20% fall in FEV1 (PD20-FEV1). The week-long trial of placebo had no effect on either baseline lung function or PD20-FEV1. On the other hand, after the 1-wk course of prednisone: (1) both baseline FEV1 and FEF25-75 systematically improved in the patients who initially had (i.e., before prednisone) lower values, and (2) PD20-FEV1 significantly increased (p less than 0.001) in all the subjects studied. The magnitude of increase in PD20-FEV1 after prednisone was significantly inversely related (i.e., inverse hyperbola) to the initial degree of airway obstruction (i.e., FEV1) obtained prior to prednisone treatment. Moreover, whereas 6 of 10 patients only minimally changed their baseline FEV1 after prednisone, collectively for all the subjects, the percent increase in PD20-FEV1 after prednisone was directly related (correlation coefficient, 0.70; p less than 0.05) to the corresponding percent increase in baseline FEV1 after prednisone. These findings demonstrate that after a week-long course of high-dose prednisone therapy: (1) a significant reduction occurs in bronchial sensitivity to inhaled methacholine in the asthmatic child, and (2) the degree of diminution in airway sensitivity to methacholine is inversely related to the patient's baseline status of airway obstruction.     

Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.     

Effect of Age on Bronchial Reactivity in Children with Asthma

In contrast to an abundance of data concerning age-related changes of bronchial sensitivity, the relationship between age and rapidity of bronchoconstriction (bronchial reactivity) remains unclear. We studied age and bronchial reactivity in children with asthma. Enrolled in this study were 511 asthmatic subjects and 115 age-matched control subjects 1 to 16 years of age. Bronchial reactivity was represented by the slope of the methacholine transcutaneous oxygen pressure dose-response curve (SPO₂) in younger children and the slope of the respiratory resistance dose-response curve (SRrs) in older children. Overall, SPO₂ and SRrs were higher in asthmatic than control subjects. SPO₂ increased significantly from 1 to 6 years in asthmatic subjects, reaching a plateau after age 7. This age-related change in SPO₂ also was seen in controls. SRrs in asthmatic subjects decreased after age 13, while SRrs in controls showed no significant change between age 7 and 16. Age-related change in bronchial reactivity occurs during childhood, possibly reflecting early changes in airway smooth muscle maturity and later changes in airway wall rigidity.     

Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records

We report the sudden death of a 16 yr old boy with asthma. At presentation, the patient had symptoms of active asthma, mild bronchoconstriction, severe airway hyperresponsiveness to methacholine, and increased variability of peak expiratory flow records. After the patient was placed on inhaled beclomethasone (1 mg b.i.d preceded by inhaled fenoterol 0.4 mg b.i.d) he rapidly felt better, lung function improved, but airway responsiveness remained severe. Four months later, on the day he died, he was well until a fatal attack of asthma occurred around midnight without identifiable precipitating factors. Taken to hospital, he was dead on arrival. Necroscopy and microscopy showed the characteristic features of asthma death. This case report suggests that; a) asthma death may occur suddenly and unexpectedly; b) asthma death may not be prevented by long-term treatment with high-dose inhaled beclomethasone; c) severe bronchial hyperresponsiveness, even in the presence of stable peak flow records, may identify asthmatic patients at risk of sudden death.     

Bronchial Reactivity to Inhaled Methacholine in Infants with Asthma and Age-Matched Controls

To evaluate bronchial hyperresponsiveness (BHR) in infants with asthma and the influence of aging on BHR during the infantile period, bronchial reactivity to inhaled methacholine (BRm) in infants was monitored using the transcutaneous oxygen pressure (tcPO₂) method. One hundred thirty-seven infants with asthma (from 1 to 5 years, mean 3.4 years) and 97 age-matched children without chronic respiratory diseases (from 6 months to 5 years, mean 2.1 years) were enrolled in this study. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO₂ from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO₂ (D_min-PO₂) was considered to represent the reactivity of tcPO₂ to inhaled methacholine. D_min-PO₂ values in the asthma groups were lower than those in the control groups in each year-group from 1 to 5. There was no statistical difference in D_min-PO₂ among the 1-4-year-old asthma groups, but D_min-PO₂ in the 5-year-old asthma group was significantly lower than D_min-PO₂ in the 1 -4-year-old asthma groups. The same age-related change in D_min-Po₂ was also seen in the control groups. There was no difference in age-related D_min-PO₂ change between the female group and the male group. We concluded that BRm in asthmatic children increases during the infantile period, and that the age-related changes in BRm, observed in both asthmatic and control infants, may have an effect on the clinical symptoms of asthma during childhood.     

The presence of airway reactivity before the development of asthma

Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.     

Effect of Age on Bronchial Reactivity in Children with Asthma

In contrast to an abundance of data concerning age-related changes of bronchial sensitivity, the relationship between age and rapidity of bronchoconstriction (bronchial reactivity) remains unclear. We studied age and bronchial reactivity in children with asthma. Enrolled in this study were 511 asthmatic subjects and 115 age-matched control subjects 1 to 16 years of age. Bronchial reactivity was represented by the slope of the methacholine transcutaneous oxygen pressure dose-response curve (SPO₂) in younger children and the slope of the respiratory resistance dose-response curve (SRrs) in older children. Overall, SPO₂ and SRrs were higher in asthmatic than control subjects. SPO₂ increased significantly from 1 to 6 years in asthmatic subjects, reaching a plateau after age 7. This age-related change in SPO₂ also was seen in controls. SRrs in asthmatic subjects decreased after age 13, while SRrs in controls showed no significant change between age 7 and 16. Age-related change in bronchial reactivity occurs during childhood, possibly reflecting early changes in airway smooth muscle maturity and later changes in airway wall rigidity.     

Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects

Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted.     

EOS、总IgE与儿童哮喘严重程度和肺功能的相关性

目的 分析血嗜酸性粒细胞(EOS)、总IgE与儿童哮喘严重程度和肺功能的相关性。方法 选择2018年1月至2021年1月我院收治并确诊的55例支气管哮喘患儿,根据病情严重程度分为轻度组18例、中度组22例、重度组15例。对比不同病情严重程度组儿童血清EOS、总IgE、FeNO及肺功能第1秒用力呼气容积占预测值百分比(FEV₁%pred)、呼气峰值流速(PEF)和用力肺活量(FVC)水平变化;观察给予吸入性糖皮质激素(ICS)治疗前后,哮喘组儿童上述指标变化情况;采用Spearman秩相关和Pearson相关性分析血清EOS、总IgE与儿童哮喘FeNO、病情严重程度及肺功能的相关性。结果 哮喘组儿童FeNO及血EOS%、总IgE水平升高,肺功能指标FEV₁%pred、PEF、FVC明显降低(P<0.05);重度哮喘组上述指标高于/低于中度组,中度组高于/低于轻度组(P<0.05)。ICS治疗后,哮喘组儿童FeNO及血EOS%、总IgE水平较治疗前降低,肺功能指标升高,治疗前后差异有统计学意义(P<0.05)。儿童哮喘血EOS%...     

Evaluation of severity of bronchial asthma through an exercise bronchial challenge

Optimum treatment of bronchial asthma requires accurate diagnosis and severity classification. We studied the use of an exercise bronchial challenge in the asthmatic patient as a diagnostic tool. An exercise bronchial challenge test was carried out in 431 asthmatic children and 114 children without a history of asthma in a moderate-altitude environment (2,230 m above sea level/7,314 feet above sea level). Values of peak expiratory flow (baseline and maximum fall) were analyzed through time in each asthma severity group (intermittent, mild persistent, moderate persistent, severe persistent, and nonasthmatic controls). There was a significant difference among responses of asthma severity groups for almost all variables. No difference was found between nonasthmatic and intermittent groups who had similar behavior, except in bronchodilator response. An exercise bronchial challenge helps classify a patient according to asthma severity; it is easy to reproduce and does not require expensive equipment. It allows diagnosing and classifying asthma severity easily and supplementing the clinical evaluation. Based on our results, we propose a fall of PEF >or= 11% as new cutoff point for making a diagnosis of persistent bronchial asthma. A fall of 11-25% indicates mild persistent asthma; from 25-50%, moderate persistent asthma; and a bigger fall, severe persistent asthma.     

Airway hyperresponsiveness: the usefulness of airway hyperresponsiveness testing in epidemiology,in diagnosing asthma and in the assessment of asthma severity

The present PhD thesis was conducted at the Respiratory Research Unit at the Pulmonary Department L in Bispebjerg Hospital, Copenhagen, Denmark and describes airway hyperresponsiveness in asthma patients in four studies. The first study concerned risk factors for the development of asthma in young adults in a 12‐year prospective follow‐up study of a random population sample of 291 children and adolescents from Copenhagen, who were followed up from the age of 7–17 years (1986) until the age of 19–29 years (1998). During follow‐up, 16.1% developed asthma, and in these subjects, the most important predictor of asthma development was airway hyperresponsiveness to histamine at baseline. Airway hyperresponsiveness is associated with more severe asthma and a poorer prognosis in terms of more exacerbations and less chance of remission of the disease. The second study described the relation between airway hyper‐responsiveness to methacholine and the quality of life in 691 asthma patients: In asthma patients with airway hyperresponsiveness to methacholine, the quality of life measured with a validated questionnaire (Junipers Asthma Quality of Life Questionnaire) was significantly reduced compared to asthma patients who did not respond to bronchial provocation with methacholine. Airway hyperresponsiveness is not uncommonly observed in non‐asthmatics, and the response to bronchial provocation with methacholine is therefore relatively non‐specific. The mannitol test is a relatively new bronchial provocation test that acts indirectly on the smooth airway muscle cells through the release of mediators from inflammatory cells in the airways; the mannitol could consequently be a more specific test compared with methacholine. The third study showed that out of 16 non‐asthmatics with airway hyperresponsiveness to methacholine, 15 did not respond to bronchial provocation with mannitol Because of the mechanism of action of mannitol, it seems plausible that the response to mannitol is more closely correlated to airway inflammation in asthma compared with the response to methacholine. The fourth study showed that in 53 adult asthma patients, who did not receive treatment with inhaled steroids, there was a positive correlation between the degree of airway inflammation and the degree of airway responsiveness to mannitol as well as to methacholine. The mannitol does, however, have the advantage of being a faster and simpler test to perform, requiring no additional equipment apart from a spirometer. Conclusions: Airway hyperresponsiveness in children and in adolescents without asthma predicts asthma development in adulthood. Asthma patients with airway hyperresponsiveness to methacholine have a poorer quality of life as well as more severe disease and a poorer prognosis compared with asthma patients without airway hyperresponsiveness. Bronchial provocation with mannitol as well as with methacholine were useful for evaluating the severity of asthma and the degree of airway inflammation, and accordingly for determining the need for steroid statement. The mannitol test does, however, have practical advantages over the methacholine test that make it preferable for clinical use.     

Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol

Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.     

Cellular events in the bronchi in mild asthma and after bronchial provocation

We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.     

A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma

Reproducibility of methacholine inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatics with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV1 greater than or equal to 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD20FEV1 using cumulative breath units (BU) were compared. The range of PD20FEV1 in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD20FEV1 less than 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occupational asthma without bronchial hyperresponsiveness

Current asthma (variable air-flow obstruction) is often excluded by the presence of normal bronchial responsiveness. We report a patient with occupational asthma that was presumed to be caused by sensitization and exposure to toluene diisocyanate (TDI). Variable air-flow obstruction measured by peak flow rates (PFR), and symptoms of asthma reversed by salbutamol, occurred after natural exposure to TDI when methacholine bronchial responsiveness was well into the nonasthmatic range. The asthma occurred at the end of, or just after work, suggesting the occurrence of late asthmatic responses. While the patient continued at work, the late asthmatic responses became progressively more severe as methacholine responsiveness progressively increased into the asthmatic range. This suggests that, in individual subjects, the degree of bronchial responsiveness is a determinant of the severity of the late asthmatic response. When the patient stopped work, spontaneous symptoms of asthma and increased diurnal variation of PFR recurred spontaneously until methacholine responsiveness returned into the normal range. These observations indicate that asthma can occur at a time when methacholine bronchial responsiveness is normal, providing the stimulus is strong enough. They further demonstrate that the magnitude and ease of bronchoconstriction relates to the degree of methacholine responsiveness.