组胺、乙酰甲胆碱检测气道高反应性不良反应比较

目的 观察组胺与乙酰甲胆碱检测气道高反应性时所出现的不良反应.方法 采用德国耶格(JAEGER)肺功能仪-支气管激发试验检测系统,对60例处于缓解期(肺功能检测正常)的轻度支气管哮喘患者,分别实施组胺与乙酰甲胆碱(乙酰甲胆碱与组胺)支气管激发试验检测.结果 .①60例支气管哮喘患者检测支气管激发试验,激发剂的选择无论是组胺还是乙酰甲胆碱均提示支气管激发试验阳性,支持存在气道高反应性;②支气管激发试验检测过程可见组胺药物不良反应明显大于乙酰甲胆碱.其不良反应程度与随着吸入药物浓度增大、吸人时间延长而增加.结论 药物支气管激发试验激发剂的选择应首选乙酰甲胆碱,组胺应慎选或不选.     

组胺、乙酰甲胆碱检测气道高反应性不良反应比较

目的 观察组胺与乙酰甲胆碱检测气道高反应性时所出现的不良反应.方法 采用德国耶格（JAEGER）肺功能仪-支气管激发试验检测系统,对60例处于缓解期（肺功能检测正常）的轻度支气管哮喘患者,分别实施组胺与乙酰甲胆碱（乙酰甲胆碱与组胺）支气管激发试验检测.结果 ①60例支气管哮喘患者检测支气管激发试验,激发剂的选择无论是组胺还是乙酰甲胆碱均提示支气管激发试验阳性,支持存在气道高反应性;②支气管激发试验检测过程可见组胺药物不良反应明显大于乙酰甲胆碱,其不良反应程度与随着吸入药物浓度增大、吸入时间延长而增加.结论 药物支气管激发试验激发剂的选择应首选乙酰甲胆碱,组胺应慎选或不选.     

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.     

Unimodal distribution of bronchial hyperresponsiveness to methacholine in asthmatic patients.

Distribution of bronchial hyperresponsiveness to methacholine was assessed in 791 consecutive patients who were referred to the outpatient clinic of the pulmonary department due to asthmatic or persistent lower airway symptoms. Bronchial asthma was diagnosed in 319 patients. Clinical sensitivity of methacholine challenge for the disease was 89 percent and specificity, 76 percent. The degree of bronchial hyperresponsiveness in the entire group of asthmatic patients was unimodally log normal distributed. Of the 82 patients with allergic rhinitis without concurrent asthma, 27 percent had bronchial hyperresponsiveness, but of a markedly lesser degree than in the hyperresponsive asthmatic patients. In 49 patients with chronic bronchitis, 22 percent had hyperresponsiveness. The present data indicate that the degree of bronchial hyperresponsiveness in asthmatic patients is unimodally distributed, supporting the view that both genetic and environmental factors have an impact upon its development. Although the degree of bronchial hyperresponsiveness in asthma is more pronounced than in allergic rhinitis or in chronic bronchitis, a marked overlap exists.     

Mannitol and AMP do not induce bronchoconstriction in eosinophilic bronchitis: Further evidence for dissociation between airway inflammation and bronchial hyperresponsiveness

Background and objective: Eosinophilic bronchitis (EB) shares many pathological features with asthma. However, patients with EB do not develop the characteristic physiological abnormalities of asthma: variable airflow obstruction and bronchial hyperresponsiveness (BHR) to a direct bronchial challenge with methacholine. Indirect bronchial challenges with AMP and mannitol are dependent on the presence of airway inflammation, and positive in 10% of asthmatic subjects who have a negative response to methacholine. We have therefore investigated whether subjects with EB are responsive to indirect airway challenge with AMP and mannitol. Methods: Subjects with asthma, EB and healthy controls attended on up to four occasions. After screening, subjects performed bronchial provocation tests to methacholine and then either AMP or mannitol. Each challenge was followed immediately by sputum induction for the measurement of airway inflammation and mast cell‐derived histamine. Results: No subjects with EB responded to either AMP (n = 5) or mannitol (n = 7) while 4/8 and 7/10 subjects with asthma responded to the respective challenges (P = 0.057 for AMP, P = 0.004 for mannitol). There was no difference in induced sputum concentrations of histamine or eosinophil cell counts following methacholine challenge compared with AMP or mannitol. Conclusions: The airways of patients with EB are not responsive to either direct or indirect bronchial challenge. This supports the view that it is the presence of functionally abnormal airway smooth muscle that is the key determinant of BHR in asthma, and that while this may be aggravated by the presence of mucosal airway inflammation, it is not caused by it.     

哮喘患者短期激素治疗前后高渗盐水激发试验PD20-FEV1的变化

目的观察哮喘患者在经过短期激素治疗后高渗盐水激发试验气道高反应性变化。方法60例哮喘患者随机分为高渗盐水组及乙酰甲胆碱组。每组30例，均短期使用布地奈德4周左右，使用剂量每日400～600微克。每组每名患者激素治疗前后做各自激发试验，测定FEV1和PD20。结果两组FFV1均改善，高渗盐水激发组气道高反应性下降，乙酰EP胆碱组无明显变化。结论哮喘患者在经过短期激素治疗后肺功能改善，高渗盐水激发试验气道高反应性下降，而乙酰甲胆碱激发试验变化不明显。高渗盐水激发试验有望在哮喘病情监测及判断疗效方面发挥作用。     

Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust

Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity.     

Longitudinal changes in bronchial hyperresponsiveness in asthmatic and previously asthmatic children.

To determine if nonspecific bronchial hyperresponsiveness is present to the same degree in previously asthmatic children compared with currently asthmatic children, a longitudinal study was conducted. On the basis of a standardized respiratory questionnaire, 139 children from asthmatic families, between the ages of 6 and 21 years, were identified. Subjects had skin tests, a serum IgE level, and a methacholine challenge test. IgE and skin tests demonstrated atopy in both the previously and currently asthmatic children, which persisted over time. Bronchial hyperresponsiveness within the asthmatic children was not significantly different between visits. Previously asthmatic children did have significantly decreased airway hyperresponsiveness over time. Age did not affect the results of the bronchial hyperresponsiveness in the currently asthmatic children. Currently asthmatic children, however, were significantly more atopic when compared with previously asthmatic children at their initial evaluation. Currently asthmatic children were also more bronchial responsive and remained so over time. Bronchial hyperresponsiveness is persistent in children with current asthma symptoms.     

对慢性喘息型支气管炎气道反应性特点及其本质的探讨

目的 研究慢性喘息型支气管炎对乙酰甲胆碱和运动激发试验的气道反应性特点,并对其本质进行初步探讨。方法 对诊断明确的支气管哮喘患者,单纯型慢性支气管炎患者及慢性喘息型支气管炎患者分别进行乙酰甲胆碱吸入激发和运动激发试验,观察血嗜酸嗜酸粒细胞计数,血ＩｇＥ水平并测定慢性喘息型支气管炎患者血肖嗜酸细胞阳离子蛋白含量。     

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.     

Monitoring asthma therapy using indirect bronchial provocation tests*

Objectives: Bronchial provocation tests that assess airway hyperresponsiveness (AHR) are known to be useful in assisting the diagnosis of asthma and in monitoring inhaled corticosteroid therapy. We reviewed the use of bronchial provocation tests that use stimuli that act indirectly for monitoring the benefits of inhaled corticosteroids. Data Source: Published clinical trials investigating the effect of inhaled corticosteroids on bronchial hyperresponsiveness in persons with asthma were used for this review. Study Selection: Studies using indirect stimuli to provoke airway narrowing such as exercise, eucapnic voluntary hyperventilation, cold air hyperventilation, hypertonic saline, mannitol, or adenosine monophosphate (AMP) to assess the effect of inhaled corticosteroids were selected. Results: Stimuli acting indirectly result in the release of a variety of bronchoconstricting mediators such as leukotrienes, prostaglandins, and histamine, from cells such as mast cells and eosinophils. A positive response to indirect stimuli is suggestive of active inflammation and AHR that is consistent with a diagnosis of asthma. Persons with a positive response to indirect stimuli benefit from daily treatment with inhaled corticosteroids. Symptoms and lung function are not useful to predict the long‐term success of inhaled corticosteroid dose as they usually resolve rapidly, and well before inflammation and AHR has resolved. Following treatment, AHR to indirect stimuli is attenuated. Further, during long‐term treatment, asthmatics can become as non‐responsive as non‐asthmatic healthy persons, suggesting that asthma is not active. Conclusions: Non‐responsiveness to indirect bronchial provocation tests following inhaled corticosteroids occurs weeks to months following the resolution of symptoms and lung function. Non‐responsiveness to indirect stimuli may provide a goal for adequate therapy with inhaled corticosteroids. Please cite this paper as: Brannan JD, Koskela H and Anderson SD. Monitoring asthma therapy using indirect bronchial provocation tests. The Clinical Respiratory Journal 2007;1:3–15.     

三种乙酰甲胆碱激发试验在成人支气管哮喘诊断中的应用

气道高反应性是支气管哮喘的重要特征.测定气道反应性对支气管哮喘的临床诊断日益重要.潮气吸人法以及定量雾化吸入法乙酰甲胆碱激发试验以第1秒用力呼气容积(FEV1)下降20%时所吸入的乙酰甲胆碱的累计药物浓度(PC20-FEV1)或总量(PD20-FEV1)来评价气道的高反应性;而Astograph法乙酰甲胆碱激发试验是以强迫振荡原理,以连续测定的呼吸阻力作为判断气道高反应性程度的指标.本文就三种激发试验对气道高反应的评价指标及在成人应用中的特点进行综述.     

Pulmonary function parameters in patients with allergic rhinitis.

Rhinitis patients may have abnormal airway function as demonstrated by an obstruction in large or small airways and increased bronchial reactivity to inhaled nonspecific provocating agents. The nonspecific bronchial hyperreactivity (BHR) is particularly important in patients with rhinitis because they are more prone to develop asthma. However, the factors associated with BHR in rhinitis patients have not yet been explained. Therefore, we performed this study to determine the differences in airflow rates, and bronchial and nasal resistance between nonasthmatic rhinitis patients with or without BHR, and to evaluate the relationship between these parameters and bronchial reactivity to methacholine. A total of 66 patients with allergic rhinitis but not asthma were selected for the study and divided into two groups; Group 1 (40 patients with allergic rhinitis and negative mechacholine provocation test) and Group 2 (26 patients with allergic rhinitis and positive methacholine provocation test). Pulmonary function tests, methacholine provocation tests, anterior rhinomanometry, and skin prick tests were performed on the patients. The study groups were homogeneous with regard to gender, age, duration of illness, and smoking ratio. Expiratory airflow parameters including FVC, FEV1, PEFR, and FEF25 were similar in both groups, however FEV1/FVC, FEF25-75, FEF50, and FEF75 were significantly lower in Group 2. Additionally, sRaw was significantly higher in Group 2 and negatively correlated with the expiratory airflow parameters for small airways. Total nasal resistance was not different between the groups. There was no correlation between nasal resistance and BHR to methacholine or airway resistance. The present study suggests that nonasthmatic rhinitis patients with BHR may have mild but significant changes in the small airways. Clinical and functional follow-up of these patients should assess the long-term consequences of these parameters and their clinical importance.     

Differences in airway responsiveness to acetaldehyde and methacholine in asthma and chronic bronchitis.

Inhaled acetaldehyde may induce bronchoconstriction in asthmatic subjects and provides a new method to investigate airway responsiveness. The objective of the study was to determine whether acetaldehyde was a more specific stimulus than methacholine in differentiating asthma from chronic bronchitis with or without airflow limitation. Bronchial provocation challenges with methacholine and acetaldehyde were performed in 62 asthmatics and in 59 smokers with chronic bronchitis (32 with chronic bronchitis alone and 27 with chronic bronchitis and coexisting chronic obstructive pulmonary disease (COPD)). The response to both bronchoconstrictor agents was measured by the provocative concentration required to produce a 20% fall in forced expiratory volume in one second (FEV1; PC20). The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) in revealing airway hyperresponsiveness in asthma. However, bronchoprovocation with acetaldehyde yielded considerably greater specificity (95%) than bronchoprovocation with methacholine (24%) in separating asthma from chronic bronchitis. In subjects with asthma, methacholine and acetaldehyde responsiveness were weakly but significantly correlated (r=0.42, p=0.001) but no correlation was found between airway responsiveness to acetaldehyde and baseline FEV1 (r=0.13, p=0.33). These findings suggest that the demonstration of bronchoconstriction in response to acetaldehyde may be a more specific test than methacholine in the differentiation of asthma from chronic bronchitis. Furthermore, methacholine and acetaldehyde hyperresponsiveness are not reflecting the same pathophysiological process in the airways.     

Lung function and airway hyperresponsiveness in adult patients with sickle cell disease

BACKGROUND: Lung disease is a major cause of morbidity and death in sickle cell disease. Although airway hyperresponsiveness has been noted in children, there are no studies in adult sickle cell patients. The aim of this study was to investigate the prevalence of airway hyperresponsiveness in adult sickle cell patients. METHODS: Twenty-six patients with sickle cell disease (10 HbSC, 9 HbSS, and 7 HbSbeta) were compared with 28 normal control subjects. Pulmonary function tests, including spirometry, measurements of single-breath diffusing capacity and the methacholine challenge test were performed. RESULTS: There were no significant differences in age, gender, or height between groups. Restrictive ventilatory defect was observed in six patients (24%) in the sickle cell disease group. Obstructive ventilatory defect and reduced diffusing lung DLCO capacity was observed in all sickle cell disease subgroups. A positive methacholine challenge test was obtained in eight (31%) sickle cell patients and in two of the 28 controls (7%). CONCLUSION: These features suggest that there is a high prevalence of airway hyperresponsiveness in adult patients with sickle cell disease without a history of reactive airway disease.     

Asthma, allergy, and airway hyperresponsiveness are not linked to the beta(2)-adrenoceptor gene

STUDY OBJECTIVES: To exclude genetic linkage between the beta(2)-adrenoceptor gene and asthma, allergy, and methacholine airway hyperresponsiveness. DESIGN: The current study used six distinct intragene markers within the beta(2)-adrenoceptor gene, and evaluated genetic linkage between the beta(2)-adrenoceptor and asthma, allergy, or methacholine airway hyperresponsiveness in eight multiplex families. PATIENTS: Forty-nine members of eight multiplex families with a high incidence of asthma. INTERVENTIONS: Phenotypes were characterized by history, physical examination, skin testing, pulmonary function tests, and methacholine inhalational challenge. Genetic loci were identified using restriction fragment length polymorphisms, denaturing gradient gel electrophoresis, and restriction enzyme digest of polymerase chain reaction-amplified fragments of the beta(2)-adrenoceptor gene. Measurements and results: Nonparametric analysis using computer analysis software found no evidence for linkage between these markers within the beta(2)-adrenoceptor gene and asthma. Parametric exclusion analysis using a dominant inheritance model resulted in large negative lod scores (- 6.74, - 19.44, and - 49.9, respectively) for tight linkage between asthma, allergy, or methacholine airway hyperresponsiveness and these polymorphic markers. CONCLUSIONS: These results indicate that asthma, allergy, and methacholine airway hyperresponsiveness are not linked to a dominant beta(2)-adrenoceptor gene with strong effect in these eight families with an inherited pattern of asthma.     

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.     

Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics.

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of LTB4 and LTC4 produced by the leukocytes of asthmatic patients on the one hand and immunoglobulin E (IgE)-mediated allergy, asthma exacerbations and bronchial hyperresponsiveness was studied. Leukocytes were obtained from peripheral blood drawn from 29 atopic and 27 nonatopic asthmatics during exacerbations and clinically controlled periods, as well as from 20 control individuals. The leukocytes were stimulated with calcium ionophore A23187 to induce LTB4 and LTC4 production. Allergy was assessed by means of specific serum IgE or by positive skin tests, whereas bronchial hyperresponsiveness was measured by methacholine challenge. The leukocytes of the asthmatics generated significantly more LTB4 (p<0.05) and LTC4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC4 was produced by leukocytes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01). In addition, there was a significant correlation between LTB4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C4 production by leukocytes is associated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B4 is closely related to bronchial hyperresponsiveness in patients with asthma.     

Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling.

To study the physiopathology and significance of asymptomatic airway hyperresponsiveness (AHR), the clinical and bronchial immunohistological parameters were evaluated in subjects with asymptomatic and symptomatic AHR. Asymptomatic subjects with AHR (eight females/two males, no respiratory symptoms, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) <8 mg x mL(-1) and no treatment) were compared with asthmatic subjects paired for age, sex and PC20, and with nonatopic, nonasthmatic controls paired for age and sex. All three groups were evaluated once at baseline, whilst the asymptomatic AHR subjects were re-evaluated after 1 and 2 yrs. Measurements included spirometry, methacholine challenge, serum immunoglobulin (Ig)E, blood eosinophils, and bronchoscopy (at baseline and after 2 yrs only). At first evaluation, the mean blood eosinophil count, total serum IgE level, atopic index, baseline forced expiratory volume in one second (FEV1) and the degree of bronchial epithelial desquamation of the asymptomatic AHR subjects were similar to those of asthmatic subjects. However, they presented focal rather than the continuous bronchial subepithelial fibrosis observed in asthmatics. Their mucosal CD3, CD4, CD25, EG1 and EG2-positive cell counts were intermediate between those of the control subjects and asthmatics. At the end of the 2-yr follow-up, four of them had developed asthma symptoms. At this time, bronchial biopsies revealed an increase in the extent of subepithelial fibrosis and in the number of CD25 and CD4-positive cells, and a decrease in the number of CD8+ cells, particularly in subjects who developed asthma symptoms. These data suggest that asymptomatic airway hyperresponsiveness is associated with airway inflammation and remodelling, and that the appearance of asthma symptoms is associated with an increase in these features, particularly the CD4/CD8 ratio and airway fibrosis. Consequently, this study proposes an association between asymptomatic airway hyperresponsiveness and airway inflammation, structural changes and asthma although these relationships remain to be further evaluated.     

The relationship between allergic rhinitis and bronchial asthma

Allergic rhinitis and bronchial asthma frequently coexist in the same patients. Many patients with rhinitis alone demonstrate nonspecific bronchial hyperresponsiveness, and prospective studies suggest that nasal allergy may be a predisposing risk factor for developing asthma. A growing body of literature has documented that the treatment of patients with allergic rhinitis may result in improvement of asthma symptoms, airway caliber, and bronchial hyperresponsiveness to methacholine and exercise. Finally, mechanistic studies of airway physiology have demonstrated that nasal disease may influence pulmonary function via both direct and indirect mechanisms. Nasal disease should be considered as a possible concomitant illness in all patients with asthma and treated appropriately when identified.