Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge

There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histamine challenge were 56%, 100%, and 77%. Furthermore, there was a statistically significant difference in the hypertonic histamine PC20 between steroid-naive and steroid-treated asthmatic subjects, which could not be detected in the isotonic histamine PC20. The hypertonic histamine PC20 was highly repeatable, with a single determination 95% range of +/-1.35 doubling concentrations. The hypertonic histamine challenge was safe but provoked more cough and throat irritation than the other two challenges. In conclusion, compared with a conventional, isotonic histamine challenge, hypertonic histamine challenge may be more accurate in the diagnosis of asthma and also, more capable to detect the effects of inhaled corticosteroid treatment.     

Usefulness of the IUATLD respiratory symptoms questionnaire for the differential diagnosis of bronchial asthma and chronic bronchitis

Our objective was to determine the diagnostic value of the questionnaire devised by the International Union against Tuberculosis and Lung Disease (IUATLD) for distinguishing between bronchial asthma and chronic bronchitis. We therefore compared clinical diagnoses established independently by two pneumologists for 211 patients to the patients' responses to the IUATLD questionnaire. The questions were analyzed for their ability to discriminate using the responses as independent variables and the diagnosis as the dependent variable. The individual predictive capacity of each question and the discriminating functions that identified the best clusters of questions were calculated using bayesian analysis. Finally, we compared IUATLD results to tests that assessed lung function (spirometry), obstruction variability (bronchodilator test, peak flow, bronchial challenge test), atopy (prick test, serum IgE), and clinical and biological markers (eosinophilia). The questionnaire correctly diagnosed 91% of the patients and a cluster of five questions registered a sensitivity of 85.6%, specificity of 91.4%, a positive predictive value of 93.1% and a negative predictive value of 82.2%, thus proving superior to the other tests. These results, along with the ease of administering the questionnaire allows us to consider the IUATLD instrument to be a good tool for the differential diagnosis of bronchial asthma and chronic bronchitis.     

Usefulness of bronchial reactivity analysis in the diagnosis of bronchial asthma in patients with bronchial hyperresponsiveness

We examined the usefulness of some bronchial reactivity indices to identify bronchial asthma in patients with airway hyperresponsiveness. Eighty-eight consecutive patients with positive response to histamine bronchial challenge (> or = 20% fall in FEV1) were included in the study. Dose-response curves were characterised by their sensitivity (PD20) and reactivity. Dose-response slope, continuous index of responsiveness (CIR) and bronchial reactivity index (BRI) with respect to baseline and post-diluent baseline values were determined as reactivity indices. The clinical diagnosis remaining in the case history 2 years after the bronchial challenge was considered the definitive diagnosis. Asthmatic patients had higher baseline BRI (12.121+/-0.412 vs. 11.615+/-0.201; P<0.001) and post-diluent baseline BRI (12.054+/-0.368 vs. 11.563+/-0.531; P = 0.003) than other subjects. Area beneath their receiver operating characteristic (ROC) curve was 82.68% (standard error: 0.77) for the baseline BRI and 81.73 (standard error: 0.76). By multiple logistic regression analysis, baseline BRI was the only independent variable identified as a predictor for diagnosis of bronchial asthma (r = 0.387, P = 0.0007). A cut-off of 11.76 for baseline BRI reached an 87.2% sensitivity and an 80% specificity for bronchial asthma diagnosis. In conclusion, BRI calculated with respect to baseline FEV1 should be useful in identifying asthmatic patients among subjects with airway hyperresponsiveness.     

容积二氧化碳图在气道反应性测定中的应用

目的 探讨容积二氧化碳图(volumetric capnography,Vcap)参数在组胺激发试验中的反应性变化并与肺通气测定法做比较.方法 对60例门诊慢性咳嗽,疑诊咳嗽变异性哮喘患者进行组胺支气管激发实验,于基础状态、每次吸入组胺后,及吸入支气管扩张药后,先进行Vcap测定,再进行肺通气功能测定.使用Vcap来评价气道反应性.结果 60例患者气道高反应性的阳性率为50%.激发试验阳性组第1秒用力呼气容积(FEV1)、最大用力呼气峰流量(PEF)及Vcap参数Threshold死腔(VDT)、Fowler死腔(VDF)、Wolff死腔(VDW)、Ⅲ期斜率(dC3/DV)在基础值和激发后值之间差异均有统计学意义(P<0.01),激发后和舒张后值之间差异也有统计学意义(P<0.05).阴性组FEV1、PEF在基础值和激发后值之间、激发后和舒张后值之间差异无统计学意义(P>0.05),VDT、VDF、VDW激发后和舒张后值之间差异有统计学意义(P<0.05).所有患者的基础值、激发后、舒张后数据,FEV1均与PEF、Vcap各参数(除dC2/DV、dC3/DV、SR23外)呈显著直线相关(P<0.05).激发试验过程中各死腔参数的下降提前于FEV1和PEF的下降.激发试验终止时,ROC曲线提示VDT、VDF为最敏感指标,VDT较基础值增加28%、VDF较基础值增加20%,可作为Vcap气道高反应性阳性判断标准.结论 Vcap是一种定量评估支气管阻塞严重性的有效方法,可应用于气道反应性测定.     

Responsiveness to three bronchial provocation tests in patients with asthma

STUDY OBJECTIVES: To compare a new bronchial provocation test, the mannitol challenge, with cold air and histamine challenges to demonstrate airway hyperresponsiveness (AHR) in patients with difficult-to-diagnose asthma. DESIGN: A prospective study. PARTICIPANTS: Thirty-seven consecutive patients with recently diagnosed, steroid-naive, mild, or atypical asthma fulfilling the diagnostic criteria of Finnish Social Insurance Institution, and 10 healthy control subjects. INTERVENTIONS: Each subject completed a symptom questionnaire and underwent spirometry, diffusion capacity measurement, skin-prick tests, and bronchial provocations with mannitol, histamine, and cold air. The severity of asthma was classified according to the Global Initiative for Asthma (GINA). RESULTS: Fifty-one percent of the asthmatic patients responded to mannitol (> or =15% fall in FEV(1)), 24% to cold air (> or =9% fall in FEV(1)), and 81% or 49% to histamine (provocative dose causing a 15% fall in FEV(1) [PD(15)] < 1.0 mg or < 0.4 mg, respectively). None of the healthy control subjects responded. The GINA classification was not associated with responsiveness to any of the challenges. CONCLUSIONS: Mannitol is more sensitive than cold air in demonstrating AHR in patients with mild or atypical asthma. Histamine was more sensitive than both mannitol and cold air if 1.0 mg was used as a cut-off value for histamine PD(15). However, if the cut-off value for histamine PD(15) is lowered to 0.4 mg, which represents a specific diagnosis of asthma according to previous studies, the sensitivity values of mannitol and histamine challenges are comparable.     

Utility of cough response during hypertonic histamine challenge in diagnosing asthma

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population. The study population consisted of 25 healthy volunteers, 30 asthmatics, and 82 non-asthmatic subjects with respiratory symptoms due to other diseases. Hypertonic histamine solution was administered with ultrasonic nebuliser with the challenges being videotaped. The cough response was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). The geometric mean (95% CI) of CCR for asthmatics was 302 (166-562) coughs per mg/ml, for the symptomatic controls 29.5 (20.0-43.7) coughs per mg/ml (p<0.001) and for the healthy controls 6.61 (3.02-14.5) (p<0.001) coughs per mg/ml. According to the ROC curve, the optimal cut-off point for logCCR was 2.22, with the specificity and sensitivity to detect asthma among symptomatic subjects being 86% and 70%. Cough response to hyperosmolar challenge may be useful in the differential diagnosis of airway diseases.     

Serum eosinophil cationic protein and bronchial responsiveness in pediatric and adolescent asthma patients.

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a marker of inflammatory activity in bronchial asthma. Bronchial responsiveness, measured either by inhaling pharmacologically active substances such as histamine or methacholine, or by applying physical stimuli such as the hyperventilation of cold dry air, is also considered to be an indirect marker of bronchial inflammation. OBJECTIVES: In this study, we investigated the possible relationship between serum ECP and bronchial responsiveness to both cold dry air and histamine in presently symptom- and medication-free pediatric and adolescent asthma patients. SUBJECTS: Thirty-six children and adolescents with atopic asthma were studied. METHODS: On 2 consecutive days, bronchial responsiveness was assessed nonpharmacologically by cold dry air and pharmacologically by histamine in random order. Blood samples for determination of ECP were collected before each challenge. RESULTS: Serum ECP levels correlated with neither cold dry air-induced changes in FEV1 nor the provocation concentrations of histamine causing a 20% fall in FEV1. Subjects with bronchial hyperresponsiveness to cold dry air and histamine had somewhat higher levels of serum ECP than subjects with normal responses, but these differences were insignificant. CONCLUSIONS: Our results indicate a lack of relationship both between serum ECP and bronchial responsiveness to cold dry air and between serum ECP and bronchial responsiveness to histamine.     

Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma

STUDY OBJECTIVES: To compare the sensitivity and validity of mannitol, histamine, and cold air challenges to demonstrate the effect of inhaled corticosteroids (ICS) in asthma. DESIGN: A prospective study. PARTICIPANTS: Seventeen patients with recently diagnosed, steroid-naive asthma who fulfilled the diagnostic criteria of Finnish Social Insurance Institution and were hyperresponsive to both mannitol and histamine. INTERVENTIONS: The following procedures were carried out at baseline and after 3 months and 6 months of treatment with inhaled budesonide, 800 microg/d: symptom assessment with a questionnaire, ambulatory peak expiratory flow (PEF) measurements twice daily for 2 weeks, and bronchial challenges with mannitol, histamine, and cold air. RESULTS: Budesonide decreased the sum symptom score, daily use of bronchodilating drugs, and diurnal PEF variation, but did not change FEV(1) percentage of predicted significantly. In addition, budesonide significantly decreased mannitol (p = 0.005) and histamine (p = 0.002) response dose ratios. The magnitude of the budesonide-induced change in responsiveness to these two challenges did not differ significantly. The effect of budesonide on cold air responsiveness did not reach statistical significance (p = 0.064). Change in mannitol responsiveness correlated significantly with the changes in sum symptom score and in FEV(1). Change in cold air responsiveness correlated with the changes in sum symptom score and in diurnal PEF variation. Change in histamine responsiveness correlated only with change in FEV(1). CONCLUSIONS: Mannitol challenge is both a sensitive and valid test to demonstrate the effects of ICS in asthma. Histamine challenge is equally sensitive for this purpose, but its validity may be lower than that of mannitol challenge. Cold air challenge seems to be a valid test to demonstrate the effects of ICS, but its sensitivity may be lower than that of mannitol and histamine challenges.     

呼出气一氧化氮检测在慢性咳嗽病因诊断中的价值

目的评估呼出气一氧化氮（FeNO）检测在慢性咳嗽患者病因诊断中的价值。方法选取2009年1月～2009年4月因慢性咳嗽在我院进行支气管激发试验的患者43例,先后予以FeNO、支气管激发试验检查。结果18例患者支气管激发试验阳性,诊断为咳嗽变异性哮喘。25例激发试验阴性患者,为非哮喘的慢性咳嗽。哮喘组患者FeNO水平显著高于非哮喘组,哮喘组患者FeNO值与LogPD20FEV1存在显著负相关性（r=-0．884）。FeNO诊断咳嗽变异性哮的最佳阈值为15．85ppb,其约登指数为0．753,灵敏度为83．3％,特异度为92．0％,阳性预计值为88．2％,阴性预计值88．5％。结论FeNO对咳嗽变异性哮的诊断具有较高的灵敏度和特异度,在慢性咳嗽的病因诊断中具有重要的应用价值。     

Bronchial challenge with aspirin lysine in the diagnosis of asthmatics with sensitization to aspirin and its inhibition by aerosolized furosemide.

We performed bronchial challenge with ASA lysine in 9 patients with a history of aspirin-induced asthma, 4 asthmatics with no history of hypersensitization to aspirin and 4 control subjects. The test consisted of successive inhalations of increasing concentrations of ASA lysine (11.25, 22.5, 45, 90, 180 and 360 mg/ml) and was interrupted when FEV1 showed a decrease of at least 20%. In order to determine the degree of bronchial hyperreactivity, we first carried out a bronchial challenge with histamine. All patients in the group sensitive to aspirin had a positive reaction to ASA lysine, while this was negative for patients in the two control groups. There was no significant correlation between PC20 to histamine and ASA lysine in any of the groups. On the other hand, 6 patients with sensitivity to ASA repeated the bronchial challenge with ASA lysine after previously inhaling furosemide, and in this second test, none of the 6 had a positive reaction. The variation of ASA lysine PC20 in both tests was positive for these patients (p < 0.001).     

Predictive value of respiratory symptoms and bronchial hyperresponsiveness to diagnose asthma in New Zealand

Respiratory symptoms are often used as the only diagnostic criteria for asthma in epidemiological surveys and the clinical diagnosis of asthma relies primarily on a detailed history. The aim of this study is to predict the diagnostic value of 11 different respiratory symptoms to diagnose asthma, and to determine if bronchial hyperresponsiveness (BHR) improves the predictive value of these respiratory symptoms. A random sample of 1257 subjects aged 20-44 years old in 3 different areas of New Zealand were selected between March 1991 and December 1992 to answer the European Community Respiratory Health Survey questionnaire on respiratory symptoms. Of these, 784 underwent bronchial challenge with methacholine. The prevalence of current doctor diagnosed asthma (DDA) defined as asthma confirmed by a physician and an asthma attack in the last 12 months was 8.3%. Wheezing with dyspnoea is the single best predictor of diagnosed asthma with a sensitivity of 82%, a specificity of 90% and a Youden's index of 0.72. Wheezing alone is more sensitive (94%) but less specific (76%), with a Youden's index of 0.70. The addition of BHR to asthma symptoms decreases sensitivity and increases specificity with a small increase in Youden's index to 0.75. In New Zealand adults, a history of wheezing with BHR best predicts a diagnosis of asthma but wheezing alone or with dyspnoea are the two best symptoms for predicting asthma.     

Astograph法支气管激发试验对哮喘诊断价值的研究

目的 评价Astograph法支气管激发试验在哮喘诊断中的价值.方法 测定80例哮喘患者和125例非哮喘患者的肺功能和气道反应性、敏感性,应用统计学方法分析两组指标间的差异,寻找能够诊断哮喘的指标及其临界值.结果 肺功能各项指标哮喘组均低于非哮喘组(FVC除外).激发试验指标Dmin和PD35哮喘组低于非哮喘组(P<0.01),但Rrs、Grs、SGrs、SGrs/Grs间的差异无统计学意义(P>0.05).哮喘组中SGrs与Dmin、PD35正相关(P<0.01;r=0.5029,0.2937).非哮喘组SGrs与PD35相关(P<0.01,r=-0.4264).以Dmin诊断哮喘,ROC曲线下面积为0.956,临界值5.9165,敏感性0.966,特异性0.925.以PD35诊断哮喘,ROC曲线下面积为0.949,临界值13.277,敏感性0.977,特异性0.895.结论 Astograph法气道激发试验有助于支气管哮喘的诊断,其中以Dmin≤5.9165 Unit或PD35≤13.277 Unit为阳性标准有较好的特异性及敏感性.     

Testing airway responsiveness using inhaled methacholine or histamine

Abstract Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV₁ (PD₂₀FEV₁) or the dose-response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut-off value of 8 mg/mL or 8 μmol for PD₂₀, the tests will discriminate asthmatic from non-asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%– as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non-specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.     

Exercise provocation test in the diagnosis of bronchial asthma and detection of airway responsiveness]

Exercise provocation test was performed on a bicycle ergometer in 110 asthmatics, 15 allergic rhinitis patients, 10 patients with moderate chronic bronchitis and 22 healthy subjects. 87.5% (21/24) of atypical asthmatics revealed positive exercise induced asthma (EIA), with the overall positive rate of asthmatics being 90% (99/110). There was a close negative linear correlation between the maximal reduction rate in FEV1 induced by exercise (delta FEV1%) and the inhaled histamine dose needed to reduce FEV1 by 20% (PD20FEV1) (r = -0.59, P less than 0.01). None of the healthy subjects, one of 15 allergic rhinitis patients and one of 10 patients with moderate chronic bronchitis showed positive response to exercise test. In contrast, seven of 18 allergic rhinitis patients and all nine patients with moderate chronic bronchitis had positive response to histamine bronchial provocation test. Therefore, exercise provocation test is a reliable method for diagnosing EIA and detecting airway responsiveness and it may possess higher specificity than histamine provocation test in diagnosing bronchial asthma, particularly in atypical bronchial asthma.     

Determination of airway hyper-reactivity in asthmatic children: a comparison among exercise, nebulized water, and histamine challenge

An easy and accurate method of assessing bronchial hyper-reactivity could be of great value in identifying and classifying the degree of severity of asthma in children. The sensitivity and specificity of three methods of provocation, ie, histamine, nebulized water, and exercise, were compared in 20 asthmatic and 20 control children between ages 5 and 13 years. Three clinical categories of severity ranging from slight (Group 1) through moderate (Group 2) to severe asthma (Group 3) were identified. The three methods were compared in each subgroup for detecting a tendency to bronchospasm. An inverse correlation (-0.57) was found between the histamine dose and clinical degree of severity, whereas distilled water and exercise proved to be too insensitive for identifying Group 1 asthmatics. Histamine challenge in children is a safe and sensitive technique for identifying asthma and for monitoring the severity of the disease during follow-up.     

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.     

The distribution of bronchial responsiveness to histamine in symptomatic and in asymptomatic subjects. A population-based analysis of various indices of responsiveness

The distribution of bronchial responsiveness (BR) and the place of symptomatic subjects in this distribution was investigated in a random population sample of 339 subjects who participated in the 1984 survey of the Vlagtwedde/Vlaardingen Study. BR was assessed by a histamine provocation test. The following indices of BR were used: (1) a histamine threshold both at 10 and at 20% decreases in FEV1 (PC10 and PC20); (2) the concentration causing a 10 or a 20% decrease estimated by linear interpolation (IPC10 and IPC20), and by linear regression of all data points (PD10 and PD20); (3) the slope of the linear regression line through all data points (SAP) and the slope of the line through the origin and the last data point (SOL). Disease was defined as the self-reported presence of respiratory symptoms from a respiratory symptom questionnaire. Bronchial challenge was considered as a test to predict symptom prevalence. Receiver-operator characteristic curves were applied to define optimal cutoff points for each of the indices used to define a positive and a negative test. For each index, sensitivity, specificity, predictive value of a positive and negative test, and efficiency rate of the test were calculated. The overall distribution of BR in this population appeared to be log normal for the different continuous indices. Subjects with symptoms were on the more responsive tail of the distribution. After adjusting for age, sex, smoking habit, and level of pulmonary function, the mean log-transformed values of PD10, PD20, SAP, and SOL for the various symptom groups differed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exhaled nitric oxide levels in military recruits with new onset asthma.

Approximately 800 United States Air Force basic military trainees (BMTs) are diagnosed with asthma, annually, resulting in separation from the military. With training costs of approximately 10,000 dollars/person, around 8 million dollarsis lost per year. Improved methods in diagnosing asthma would be beneficial. The aim of this study was to determine the fraction of exhaled nitric oxide (FENO), a marker of airway inflammation, in a military recruit population referred for an asthma evaluation. In BMTs referred for respiratory complaints during basic training, FENO levels were determined before an asthma evaluation consisting of a history, physical, baseline spirometry, and histamine bronchoprovocation. Of 172 BMTs who had symptoms suggestive of asthma and underwent histamine bronchoprovocation, 80% were diagnosed with asthma. FENO levels were significantly higher in asthmatic patients than nonasthmatic patients (mean, 30 parts per billion [ppb] versus 19 ppb, p < 0.001; median, 21 ppb versus 17 ppb, p < 0.02). Various FENO cutoff points provided a range of sensitivity and specificity for the diagnosis of asthma. However, an optimal FENO cutoff level for asthma was not obtained. An FENO value of 10.5 ppb provided a sensitivity of 86% for the diagnosis of asthma, but specificity was only 21%. In contrast, an FENO value of 46 ppb provided 100% specificity but only 17% sensitivity. FENO levels were significantly elevated in BMTs diagnosed with asthma but the lack of an optimal cutoff level limits the test as a diagnostic tool for asthma. Additional studies are necessary to determine the value of FENO for asthma screening in a military population.     

Lung function, bronchial responsiveness, and asthma in a community cohort of 6-year-old children

Children as young as 6 years old can perform spirometry, yet the relationship between current asthma, lung function, and bronchial responsiveness has not been described at this age; 2,537 children from a community-based birth cohort were assessed at 6 years of age, with history (n = 2,141), physical examination (n = 1,995), standard spirometry (n = 1,735), and a random sample (n = 711) offered methacholine challenge. Males had greater values of FVC and FEV(1) but not of mean forced expiratory flow during the middle half of the FVC or FEV(1)/FVC than females. The greatest influences on lung function at 6 years were height, sex, birth weight, and wheezing in the first year of life. Children with current asthma had small but significant deficits in lung function and were more sensitive to methacholine. The optimal cutpoint for determining heightened bronchial responsiveness was found to be a 15% fall in FEV(1) at a dose of 1.8 mg/ml. A negative test could be useful in excluding a diagnosis of asthma (negative predictive value of 92%). Lung function testing, including methacholine challenge, is feasible in 5- to 7-year-old children and has the potential to contribute to the clinical management of children with asthma.Keywords:     

Lack of airway response to nasal irritation in normal and asthmatic subjects

Abstract Twenty two subjects (10 normals, nine asthmatics and three who had suggestive histories for asthma but normal bronchial histamine challenges) underwent nasal challenges with logarithmic incremental doses of histamine or saline on alternate days. Nasal resistance (measured by posterior rhinometry), and forced expiratory volume in one second (FEV₁) were assessed after each dose of nasal histamine or placebo. After each nasal challenge (maximum nasal dose of 250 μg of histamine or doubling of nasal resistance) bronchial responsiveness was measured with a bronchial histamine challenge. Despite significant changes in nasal resistance with nasal histamine (p < 0.01) there was no significant change in the forced expiratory volume in one second, or in bronchial responsiveness. We were unable to demonstrate nasobronchial reflexes initiated by acute irritation of the nasal mucosa with histamine in either normal subjects or in those with mild to moderate asthma.