Percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV1 in symptomatic asthma and clinical remission during adolescence

BACKGROUND: Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in approximately one half of these subjects. BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20). The percentage fall in FVC at the PC20 (deltaFVC) has been suggested to be a more useful index of disease severity in asthma than PC20. STUDY OBJECTIVE: The aim of this study was to determine whether deltaFVC is higher in adolescents with symptomatic asthma than in those with clinical remission. PATIENTS AND METHODS: Forty adolescents with symptomatic asthma and 80 adolescents with asthma remission underwent methacholine challenge testing. DeltaFVC and PC20 were measured on the methacholine dose-response curve. RESULTS: The mean (95% confidence interval [CI]) deltaFVC (15.5% [95% CI, 14.1 to 16.9%]) in the symptomatic group (n = 40) was significantly higher (p = 0.017) than that (12.8% [95% CI, 11.5 to 14.1%]) in the BHR-positive (PC20 < 16 mg/mL) remission group (n = 44) or that (11.5% [95% CI, 10.2 to 12.8%]) of the BHR-negative remission group (n = 36), with no difference between the two latter groups (p = 0.581). No significant correlation was found between deltaFVC and PC20 in the symptomatic group (r = -0.156, p = 0.336) or in the whole remission group (r = -0.187, p = 0.097). CONCLUSIONS: Adolescents with symptomatic asthma had a higher deltaFVC than those with clinical remission, irrespective of the presence of BHR in the latter group. This finding suggests that deltaFVC may serve as an adjunct marker for differentiating between asthma persistence and remission during adolescence.     

Calculation of provocative concentration causing a 20% fall in FEV(1): comparison of lowest vs highest post-challenge FEV(1)

BACKGROUND: Considerable, unexamined controversy exists surrounding the use of the highest vs the lowest FEV(1) for calculating the provocative concentration causing a 20% fall in FEV(1) (PC(20)) during direct bronchoprovocation challenges. OBJECTIVE: To compare the PC(20) calculated using the lowest FEV(1) post-diluent and post-histamine/methacholine vs the PC(20) calculated using the highest FEV(1) post-diluent and post-histamine/methacholine. METHOD: Retrospective analysis of 225 challenges: 75 research methacholine challenges, 75 research histamine challenges, and 75 clinical methacholine challenges. For each test, the PC(20) was calculated twice, first using the lowest post-diluent FEV(1) to the lowest post-histamine/methacholine FEV(1), and then using the highest to the highest. RESULTS: The intraclass correlation coefficients for methacholine research, histamine research, and methacholine clinic challenges were 0.99, 0.98, and 0.95, respectively. The PC(20) calculated using the lowest to lowest FEV(1) was slightly and significantly lower in all three groups (paired t test p < 0.0001). CONCLUSIONS: The PC(20) values calculated using the highest FEV(1) are almost identical to the PC(20) values calculated using the lowest FEV(1). The difference, although clinically irrelevant, holds statistical significance.     

Comparison of Delta FVC (% decrease in FVC at the PC(20)) between cough-variant asthma and classic asthma.

The percentage decrease in forced vital capacity (FVC) at the methacholine PC(20) (Delta FVC) has been proposed as a surrogate marker of maximal airway response. The aim of this study was to compare the Delta FVC between patients with cough-variant asthma (CVA) and those with classic asthma (CA). We performed a retrospective analysis of methacholine challenge test data from 47 children who were diagnosed as having CVA and from 75 children who had CA of mild severity. The mean (+/- SD) Delta FVC was significantly (p = 0.001) lower in the CVA group (14.7 +/- 3.4%) compared with the CA group (17.1 +/- 4.4%), whereas PC(20) was not different between the two groups. Our results suggest that CVA is associated with a lower level of maximal airway response than CA.     

Comparison of Δ FVC (% Decrease in FVC at the PC20) Between Cough-Variant Asthma and Classic Asthma

The percentage decrease in forced vital capacity (FVC) at the methacholine PC₂₀ (Δ FVC) has been proposed as a surrogate marker of maximal airway response. The aim of this study was to compare the Δ FVC between patients with cough-variant asthma (CVA) and those with classic asthma (CA). We performed a retrospective analysis of methacholine challenge test data from 47 children who were diagnosed as having CVA and from 75 children who had CA of mild severity. The mean (± SD) Δ FVC was significantly (p = 0.001) lower in the CVA group (14.7 ± 3.4%) compared with the CA group (17.1 ± 4.4%), whereas PC₂₀ was not different between the two groups. Our results suggest that CVA is associated with a lower level of maximal airway response than CA.     

Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma

It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma. Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a double-blind, randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)-PEF(40) values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.     

FEV1/FVC ratio of 70% misclassifies patients with obstruction at the extremes of age

BACKGROUND: The American Thoracic Society recommends using the lower limit of normal (LLN) method to diagnose obstructive lung disease. However, few studies have investigated the clinical relevance of these recommendations. We compared the LLN derived from available data sets to a fixed ratio (FEV1/FVC, < 75% or 70%) and also to the FEV1/FVC percent predicted ratio to determine the impact of changing the FEV1/FVC "cutoff" on the spirometric diagnosis of obstructive lung disease. METHODS: FEV1, FVC, FEV1/FVC ratio, age, race, sex, height, and weight were recorded from 1,503 pulmonary function tests. Predicted values were calculated using the Third National Health and Nutrition Examination Study data set (Hankinson), and reference values from studies by Crapo, Knudson, and Morris. In addition, the LLN of the FEV1/FVC ratio was calculated for the Hankinson and Crapo reference values. RESULTS: The number of studies interpreted as obstructed varied from 37% using the Hankinson data set to 55% using the 75% fixed ratio method. Comparing the LLN method vs the 70% fixed ratio method resulted in 7.5% (Hankinson LLN vs 70% fixed) and 6.9% (Crapo LLN vs 70% fixed), which were discordant results. Age was the strongest predictor of discordance, and 16% of subjects > 74 years of age had discordant results comparing Hankinson values to the 70% fixed method. CONCLUSION: At the extremes of age and height, a large number of spirometry test results will be interpreted as showing an obstructive defect if a 70% fixed ratio method is used for interpretation compared with the LLN derived from the Hankinson data set.     

The relationship between delta-forced vital capacity (percent fall in forced vital capacity at the PC20 dose of methacholine) and the maximal airway response in patients who have mild asthma.

Airway hypersensitivity is routinely evaluated by measuring the concentration (PC20) of inhaled methacholine or histamine that causes a 20% fall in forced expiratory volume in 1 second (FEV1). It has been suggested that a percentage fall in forced vital capacity (FVC) measured at the PC20 dose of inhaled agonist (deltaFVC) is a potentially useful clinical measure in patients who have asthma because it provides indirect information about gas trapping and therefore the maximal airway response. The relationships between serum eosinophil cationic protein (ECP) levels and the maximal airway response or deltaFVC are largely unknown. The aims of this study were to determine whether deltaFVC is correlated with the degree of maximal airway response and to examine the relationships between serum ECP and deltaFVC or maximal airway response in patients who have mild asthma. Fifty-eight patients with mild asthma underwent high-dose methacholine challenge testing. The PC20, maximal airway response, and deltaFVC were measured on the methacholine dose-response curves. Serum ECP levels also were determined. Subjects without a maximal response plateau (n = 33) had a significantly higher level of deltaFVC (17.9 +/- 4.1%) than subjects with a plateau (n = 25; 14.9 +/- 4.8%). A significant correlation was found between deltaFVC and the level of maximal response plateau (r = 0.446; p = 0.026). Not only methacholine PC20 but also maximal airway response or deltaFVC had no relationships with serum ECP levels. Our results suggest that deltaFVC can be used as a surrogate marker of maximal airway response in patients who have mild asthma and that neither maximal airway response nor deltaFVC reflects blood eosinophil activation any more than methacholine PC20.     

Effect of azithromycin on the severity of bronchial hyperresponsiveness in patients with mild asthma.

The effect of azithromycin on bronchial hyperresponsiveness was measured in a group of 11 patients with mild asthma. Azithromycin 250 mg orally was administered intermittently to all the patients twice a week for eight weeks. The only other treatment was inhaled beta2 agonist, when required. A histamine inhalation test was performed at the beginning and at the fourth and the eighth week of the study. The mean PC20 values increased significantly over the initial value at the eighth week after the administration of azithromycin (p < 0.05) but mean values for FEV1 and FEV1 percent predicted did not differ significantly. These results suggested that eight weeks of intermittent, low-dose administration of azithromycin in patients with mild asthma might reduce the severity of bronchial hyperresponsiveness.     

Effects of HFA- and CFC-beclomethasone dipropionate on the bronchial response to methacholine (MCh) in mild asthma

Metered inhalers using chlorofluorocarbon (CFC) propellents have been gradually replaced by new devices that use hydrofluoroalkanes (HFAs) as their propellents, which are less harmful to the environment. This reformulation led to a substantial improvement of the previous technologies applied to inhalation devices and of the physical characteristics of drugs delivered. In particular, inhaled corticosteroids, such as beclomethasone dipropionate (BDP) which is of fundamental importance in the long-term management of bronchial asthma, took advantage of this reformulation. Unlike the preparation beclomethasone dipropionate and chlorofluorocarbon (BDP-CFC) which was a suspension, that of beclomethasone dipropionate and a hydrofluoroalkane (BDP-HFA) is a solution and produces an aerosol with a mean aerodynamic particle size of 1.1 microm, which is much smaller than the particle size of 3.5-4.0 microm, obtained with the BDP-CFC. The particles of BDP-HFA can then deposit in the lungs in a larger amount, and particularly in the more peripheral airways where the inflammatory process starts in the case of bronchial asthma. A 12-week use of BDP-HFA ensured a significant better control of the bronchial response to methacholine (MCh) than the corresponding use of BDP-CFC for the same duration. The therapeutic performance of BDP-HFA proved much higher and allowed the substantial reduction of the therapeutic daily dose for the clinical asthma management, being the increased and more peripheral deposition of BDP-HFA is presumed to play a crucial role.     

Mediator concentrations in bronchoalveolar lavage fluid of patients with mild asymptomatic bronchial asthma.

Bronchoalveolar lavage (BAL) was performed on 11 atopic patients with mild asymptomatic bronchial asthma and 11 healthy nonasthmatic volunteers. All asthmatic subjects had evidence of bronchial hyperresponsiveness to inhaled carbachol. The concentrations of leukotriene (LT) C4, LTD4, LTE4, LTB4, prostaglandin D2 (PGD2), platelet-activating factor (PAF) and histamine in BAL fluid measured. The leukotrienes were measured by radioimmunoassay following reverse phase high performance liquid chromatography. PGD2 concentrations were determined by radio immunoassay after Amprep C2 extraction. PAF was quantitated by means of in vitro aggregation of rabbit platelets and histamine content was measured using a single isotope radio-enzymatic assay. There was an increase in the levels of PGD2 and a decrease in the concentration of LTB4 in asthmatic lavage samples. There were no significant differences in the lavage concentrations of LTC4/D4/E4 and histamine between the two groups of individuals. PAF was undetectable.     

Absence of hyperresponsiveness to methacholine in a worker with methylene diphenyl diisocyanate (MDI)-induced asthma

A 29-year-old man had a persuasive history of respiratory illness following exposures to methylene diphenyl diisocyanate (MDI). He was evaluated by measuring bronchial reactivity to methacholine, both before and after controlled laboratory exposures to MDI. Despite evidence of progressive declines in FEV1 with increasing (but subirritant) doses of MDI on three consecutive days, there was no bronchial hyperresponsiveness to methacholine, before or after MDI challenge. We conclude that the absence of nonspecific bronchial hyperresponsiveness does not exclude the possibility of isocyanate asthma. In the face of a compelling history, a negative result of methacholine challenge should not deter observation or laboratory testing for specific respiratory allergy to these chemicals.     

A longitudinal study of baseline FEV1 and bronchial responsiveness in patients with asthma.

The effect of initial airway calibre on the response to bronchial provocation is unclear. Theoretically, geometric relationships within the airways might influence the measurement of responsiveness, particularly since a given change in calibre will produce a disproportionately greater reduction in flow in airways which are already narrowed. We have examined the relationship between serial measurements of prechallenge forced expiratory volume in one second (FEV1) and responsiveness to methacholine (PD20) in 8 children and 12 adults with asthma. Measurements were made every 2-3 wks for 12-18 months and all patients kept a daily record of symptoms and twice daily measurements of peak expiratory flow (PEF). Spearman's rank correlation coefficient (rho) for the relationship PD20 versus pre-challenge FEV1 was derived for each patient and varied widely within the group (range -0.22 to 0.73, mean 0.31); the strength of this correlation was not related to a patient's mean FEV1 % predicted, but was related to the degree to which PD20 and pre-challenge FEV1 themselves reflected concurrent asthma severity (mean morning PEF and mean symptom scores for the three days around each test). This suggests that the observed relationship between pre-challenge FEV1 and PD20 may be due less to the influence of airway geometric factors, which might be expected to be present in all patients, but rather that pre-challenge FEV1 is reflecting the severity of the underlying disease. Larger studies will be needed to test this hypothesis further.     

Specific airway resistance is a better outcome parameter in bronchial provocation testing compared to FEV1 in patients with bronchial asthma

Objectives: Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for AHR. However forced expiratory volume in one second (FEV₁), used as outcome parameter is effort-related, in contrast to specific airway resistance (sRaw). This research was conducted to provide insight in the usefulness of sRaw as an outcome parameter in BPT. Methods: A total of 85 patients performing a BPT were included in the study. Bronchial reactivity was defined as the provocative dosage or provocative concentration causing a 20% decrease in FEV1 (PC-20) or a 100% increase in sRaw (PC+100). Results: No significant response in either FEV₁ or sRaw was found in 20 patients (24%). Twenty-nine patients (34%) only had a positive response for sRaw; 24 out of these 29 patients recognized their symptoms. 36 patients (42%) showed a positive response for both PC-20 and PC + 100. Conclusions: Twenty-nine patients (34%) showed a significant increase in sRaw without a fall in FEV₁. As performing sRaw is not a routine investigation, these patients are at risk of being excluded from a diagnosis of asthma. We suggest performing sRaw for patients without a fall in FEV₁ during BPT when they report recognizable symptoms.     

Comparison between peak expiratory flow and FEV(1) measurements on a home spirometer and on a pneumotachograph in children with asthma

BACKGROUND: The accuracy of electronic portable home spirometers has been demonstrated in vitro using computer-based waveforms. We assessed the agreement in vivo between measurements of lung function on an electronic spirometer (Koko Peak Pro) and those obtained by the gold standard, a hospital lung function laboratory pneumotachograph. METHODS: Fifty stable asthmatic children (33 boys), aged 6-17 years, performed peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) measurements according to international guidelines on a portable home spirometer and on the hospital pneumotachograph in random order. All measurements complied to standard quality criteria. The PEF and FEV(1) values recorded with the home spirometer and on the hospital pneumotachograph were compared. RESULTS: All children performed reproducible high-quality measurements on both spirometers. PEF values on the home spirometer were considerably lower than on the laboratory pneumotachograph (95% CI for difference in PEF 14-30 L/min; P < 0.0001). Individual differences in PEF between the two devices could be >100 L/min. The FEV(1) values were slightly, but significantly, lower on the home spirometer (95% CI for difference in FEV(1) 0.02-0.1 L; P = 0.0018). CONCLUSIONS: A home spirometer provides reproducible and quality acceptable measures in children with asthma when performed under professional supervision and encouragement. Mean PEF and FEV(1) values recorded on this home spirometer are significantly lower than those on a hospital pneumotachograph, and individual differences may be large. Therefore, home spirometry may not be interchanged with pneumotachography in a lung function laboratory.     

Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.     

Association between a sequence variant in the IL-4 gene promoter and FEV(1) in asthma.

Recent family-based studies have revealed evidence for linkage of human chromosome 5q31 to the diagnosis of asthma, elevated serum IgE levels, and bronchial hyperresponsiveness. Among the candidate genes in this region is the gene encoding for human interleukin-4 (IL-4). We reasoned that this gene could also serve as a candidate gene with respect to asthma severity as indicated by the FEV(1) measured when bronchodilator treatment was withheld. To test this hypothesis, we examined a large population of patients with asthma (ascertained without respect to genetic characteristics), for associations between a genetic variant in the IL-4 promoter region (C-589T) and asthma severity, as indicated by FEV(1). We used amplification by the polymerase chain reaction followed by BsmF1 restriction digestion to assign genotypes at the IL-4 promoter C-589T locus. We compared genotypes at this locus in 772 Caucasian and African American patients with asthma of varying severity, and we used multiple regression analysis to relate genotypic findings to FEV(1). Among white individuals, the homozygous presence of the C-589T IL-4 promoter genotype (TT) was associated with a FEV(1) below 50% of predicted (p = 0.013; OR, 1.44; 95% CI: 1.09 to 1.90). Subjects with the TT genotype had mean FEV(1) (% predicted) values 4.5% lower than those of subjects with the wild-type (CC) genotype at this locus. FEV(1) values of white patients with a CC or CT genotype were broadly distributed, whereas the TT genotype was associated with a narrow distribution of low FEV(1) values. The frequency of the T allele was significantly greater (p = 1 x 10(-)(23)) among African American asthmatics (0.544) than among white asthmatics (0.183). These data provide the first evidence associating FEV(1) in patients with asthma and genetic determinants at any locus. Our data are consistent with the idea that the FEV(1) in asthma is the result of multiple factors; one of these factors is the genotype at the IL-4 C-589T locus. This locus is associated with a small but significant decrement in pulmonary function among white asthmatic subjects.     

Postural stability in school-age children with mild bronchial asthma disease (a pilot study)

Objective: This study assessed the postural stability in children with asthma using balance tests under conditions of a comfortable foot placement and with a foot placement provoking instability. Methods: A group of 10 school children from 8 to 10 years old with mild intermittent asthma and 10 healthy children of the same age range performed four balance tests in a randomized order: preferred stance, adjusted stance, and tandem stance each under both conditions of eyes opened (EO) and eyes closed (EC), as well as a one-legged stance with eyes-opened conditions. To determine postural stability, the center of pressure (CoP) movement was recorded. Basic stabilographic parameters were calculated: CoP velocity in the anterior–posterior direction, CoP velocity in the medial–lateral direction, and the total CoP velocity. Results: Statistically significant differences between the groups were found only for the one-legged stance. Significantly greater anterior–posterior CoP velocity (p?=?0.05) and total CoP velocity (p?=?0.03) were found in children with asthma when standing on the preferred foot. A significantly greater medial–lateral velocity (p?=?0.02) was also found in the non-preferred foot of children with asthma. Conclusions: We can conclude that standing on one leg might be an appropriate test with which to identify balance differences between young children with mild intermittent asthma and healthy children.     

Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV(1) responses, and methacholine inhalation challenges in the evaluation of suspected asthma

STUDY OBJECTIVES: The validity of peak expiratory flow variation (PEFvar) as defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines as a diagnostic tool for suspected asthma or its comparative value to methacholine inhalation challenge (MIC) or postbronchodilator (BD) FEV(1) responses has not been formally assessed. We prospectively analyzed the correlation of 28 different PEFvar indexes (including 4 NHLBI-compatible indexes) with MIC and pre-BD and post-BD FEV(1) responses in suspected asthmatic subjects with normal findings on lung examination, chest radiography, and baseline spirometry. DESIGN: Participants were asked to record peak expiratory flow four times daily for 2 to 3 weeks, followed by an MIC. During a minimum 6-month follow-up period, a clinical diagnosis of asthma was made or ruled out based on testing results and response to antiasthma therapy. SETTING: Medical school-affiliated subspecialty private practice of allergy, asthma, and immunology. PARTICIPANTS: One hundred twenty-one suspected asthmatic patients with normal findings on lung examination, chest radiography, and baseline spirometry. MEASUREMENTS AND RESULTS: Fifty-seven subjects completed both the peak flow diary and the MIC and were accepted for statistical analysis. There were no statistically significant correlations between any peak expiratory flow index and MIC. Among the three diagnostic tools evaluated, MIC had the highest sensitivity (85.71%). All the PEFvar indexes and post-BD responses had low sensitivity and high false-negative rates. CONCLUSIONS: PEFvar and post-BD FEV(1) responses are poor substitutes for MIC in the assessment of patients with suspected asthma with normal findings on lung examination, chest radiography, and spirometry. Our findings warrant a reconsideration of the NHLBI guidelines recommendation of the utility of PEFvar as a diagnostic tool for asthma in clinical practice.     

Effect of inhaled ipratropium bromide on the airway response to methacholine, histamine, and exercise in patients with mild bronchial asthma.

We studied the bronchodilator and protective potency of inhaled ipratropium bromide in 33 patients with mild bronchial asthma. Patients were divided into 3 groups with similar baseline lung function and similar degrees of bronchial hyperresponsiveness to participate in the methacholine (study I, n = 9), histamine (study II, n = 9), or exercise challenge tests (study III, n = 18). At each session, 80 micrograms ipratropium bromide or placebo were inhaled in a double-blind randomized fashion. After ipratropium bromide, the mean specific airway resistance (SRaw) decreased from 10.4 to 4.9 (study I, p less than 0.01), 9.3 to 5.4 (study II, p less than 0.05), or 7.8 to 5.1 cm H2O.s (study III, p less than 0.01), respectively. Mean methacholine provocation concentrations necessary to increase SRaw by 100% were 0.43 after placebo and 8.60 mg/ml after ipratropium bromide (p less than 0.01), the respective values after histamine challenges were 1.32 mg/ml after placebo and 2.25 mg/ml after ipratropium bromide (p less than 0.01). In the exercise challenges, the individual responses varied largely with a mean maximum percent increase in SRaw of 231% after placebo and 173% after ipratropium bromide pretreatment (p less than 0.05). Therefore, ipratropium bromide offers bronchodilation and protection against a variety of stimuli and should more often be considered as an effective and safe drug for asthma treatment.     

呼出气一氧化氮浓度测定对变应性鼻炎合并下气道高反应性或哮喘的预测及辅助诊断价值研究

目的 探讨呼出气一氧化氮浓度(FeNO)测定对变应性鼻炎合并无症状的下气道高反应性患者或非急性发作期(慢性持续性)哮喘患者的预测及诊断价值。方法 对广州医科大学附属第一医院呼吸科收治的20例变应性鼻炎患者、15例变应性鼻炎合并无症状的下气道高反应性患者及20例变应性鼻炎合并非急性发作期(慢性持续性)哮喘患者(年龄18～50岁)进行FeNO测定、鼻腔灌洗细胞分类计数、诱导痰细胞分类计数以及乙酰甲胆碱支气管激发试验,分析各项指标的分布特点及相关性,探讨FeNO测定对变应性鼻炎患者合并无症状支气管高反应性(BHR)或非急性发作期(慢性持续性)哮喘的预测及下气道炎症的评估。结果 FeNO值的中位数和四分位间距在单纯变应性鼻炎组、变应性鼻炎合并无症状下气道反应性增高组、以及鼻炎合并哮喘组分别为24.0(15.5,35.5)pg/L、46.5(35.0,63.0)pg/L和61.5(39.0,75.0)pg/L,3组间差异具有统计学意义(P<0.01)。以测定的FeNO值为标准对变应性鼻炎患者下气道高反应性进行判断,绘制ROC曲线(AUC=0.842,P=0.002),以34.0 pg/L为截断点则敏感度为75.0%,特异度为73.7%。以FeNO值对变应性鼻炎合并哮喘诊断的ROC曲线(AUC=0.887,P=0.000),FeNO值取41.0 pg/L时对变应性鼻炎合并哮喘诊断的敏感度为75.0%,特异度为83.1%。诱导痰中嗜酸性粒细胞(EOS)在单纯变应性鼻炎组、变应性鼻炎合并无症状下气道反应性增高组以及鼻炎合并哮喘组分别为(2.43±3.56)%、(7.36±4.98)%及(18.5%±11.26)%,3组间差异具有统计学意义(P<0.01)。结论 变应性鼻炎患者可伴有一定程度的下气道炎症,且与下气道高反应性密切相关。FeNO测定简便、稳定,对变应性鼻炎患者合并下气道高反应性或哮喘具有良好的预测和辅助诊断作用。