Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up

The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.     

Prednisolone Hastens Recovery from Histamine-Induced Bronchospasm in Asthmatics

Short-term treatment with oral steroids is very effective in controlling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV₁] and concentration of histamine causing a 20% reduction FEV₁ [PD₂₀ FEV₁]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD₂₀ FEV, values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean ± SD time for 95% recovery from histamine-induced bronchospasm was 33.00 ± 19.47 min before treatment and decreased significantly to 18.00 ± 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.     

Exhaled Nitric Oxide and Bronchial Wall Thickening in Asthmatics During and After Acute Exacerbation: Evidence of Bronchial Wall Remodeling

To assess whether bronchial wall thickening during asthma exacerbations is due to active inflammation in severe asthmatics, we measured bronchial wall thickness and exhaled nitric oxide (FeNO) following treatment. Nine asthmatics were compared with seven controls with high-resolution computed tomography, spirometry, and FeNO measurements. The asthmatic bronchial wall area percent and FeNO was greater than controls. Following treatment, the FEV₁ markedly improved, FeNO decreased modestly, and bronchial wall area percent did not change significantly. Bronchial wall thickening persisted after treatment of acute asthma exacerbation despite improvement in spirometry and decline in FeNO, possibly due to chronic airway remodeling.     

Acute Bronchodilator Response Has Limited Value in Differentiating Bronchial Asthma from COPD

Background. Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV₁ and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology. Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results. None of the expressions of response gave a clear-cut separation between the two diseases. A ΔFEV₁≥ 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (ΔFEV₁%predicted ≥ 9% and ΔFEV₁ of ≥ than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions. It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD.     

Value of Bronchial Challenge in Scuba Diving Candidates

Bronchial challenges were effected with carbachol in 76 subjects who were candidates for a scuba diving group. Bronchial reactivity was assessed through airway resistance and forced expiratory volume in 1 sec (FEV₁) measurements. Medical interrogation had revealed symptoms of recent (RA) or ancient (AA) asthma, or allergic rhinitis (AL). Nearly half of the subjects (47%) presented bronchial hyperresponsiveness (BHR), which was much more frequent in the RA group, but whose strength did not depend on clinical presentation. Prevalence of BHR was fairly high (36%) in the AL group. BHR constituted a contraindication to scuba diving because it may promote pulmonary barotrauma.     

A Bronchial Response Comparison of Exercise and Methacholine in Asthmatic Subjects

The authors compared the inhaled methacholine and exercise responses in 22 stable unmedicated asthmatic patients. The exercise and methacholine challenges were performed at one to three week intervals. Bronchial responsiveness to methacholine was measured in relation to the concentration of methacholine (PC₂₀M). The response to exercise was expressed as the percentage of fall in FEV₁, from the pre-exercise FEV₁ The findings showed that 21 of 22 subjects demonstrated a fall in FEV₁, of more than 20% after methacholine challenge, while only 9/22 subjects experienced a similar decrease in FEV₁. All 9 of these positive response exercise cases completed three consecutive exercise challenges prior to the methacholine challenge. Of these cases, five were refractory to the repeated exercise challenge, and the PD₂₀M at the nonexercise stage was significantly lower than the postexercise state. In fact, the methacholine challenge sensitivity actually decreased (PD₂₀ increased) after repeated exercise. The authors concluded that methacholine seems to be a more sensitive bronchial provocation test than exercise. Second, only 55.6% of the exercise test-positive subjects were refractory to the second exercise challenge. Therefore, other factors besides the release of mediators should be considered in exercise induced asthma. Third, methacholine sensitivity actually decreased (PD₂₀ increases) after repeat exercise challenge.     

ACO患者血清Fbg、FeNO、IgE水平变化与肺功能相关性研究

目的探讨支气管哮喘-慢性阻塞性肺疾病重叠综合征(ACO)患者血清中纤维蛋白原(Fbg)、呼出气一氧化氮(FeNO)、免疫球蛋白E(IgE)的变化水平与肺功能的相关性。 方法选择2016年1月至2018年5月期间在我院接受治疗的支气管哮喘急性发作期患者56例,慢阻肺急性加重期患者51例,ACO急性加重期患者45例,同时选取50例健康者作为对照。检测受试对象的外周血嗜酸性粒细胞数量、Fbg和IgE水平、FeNO以及肺功能指标。采用Pearson相关性分析Fbg、FeNO、IgE与1 s用力呼气容积(FEV₁),FEV₁改善值,用力肺活量(FVC)的关系。绘制受试者工作特征(ROC)曲线,并计算Fbg、FeNO、IgE指标曲线下面积(AUC)。 结果①三组患者嗜酸性粒细胞数量和血浆IgE水平明显高于对照组(P<0.05);但是三组患者之间比较,未见统计学差异(P>0.05)。ACO患者血清Fbg水平高于哮喘组患者(P<0.05),FeNO检测值高于慢阻肺患者(P<0.05);②ACO患者FEV₁、FEV₁改善值和FVC值明显高于对照组和慢阻肺组受试者,但是FEV₁值高于哮喘组患者,而FEV₁改善值和FVC值低于哮喘组患者(P<0.05);③ACO患者血浆Fbg水平与FEV₁、FEV₁改善值和FVC值均呈负相关性(P<0.05),而FeNO值仅与FEV₁值呈负相关性(P<0.05)。而血浆IgE水平与FEV₁改善值呈正负关性(P<0.05);④经ROC曲线分析,Fbg、FeNO、IgE联合检测ROC曲线的AUC为0.892(95%CI：0.773-0.948),敏感性和特异性分别为89%和78%。 结论Fbg、FeNO和IgE与ACO患者肺功能指标密切相关,有助于临床鉴别ACO、支气管哮喘以及慢性阻塞性肺疾病。     

Airway responses to salbutamol after exposure to chemical warfare

Background and objectives:   Increased airway responsiveness to β-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.
Methods:   The threshold concentrations of inhaled salbutamol required for a 20% change in FEV₁ as PC₂₀, or a 35% change in specific airway conductance (sGaw) as PC₃₅ were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.
Results:   In 11 of the 22 subjects PC₂₀ salbutamol could be measured and in 15 of the 22 subjects PC₃₅ salbutamol could be measured. This group of patients was the responder group (PC₂₀ = 10.79 and PC₃₅ = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC₂₀ = 237.68 and PC₃₅ = 88.72 mg/L, P  < 0.001). There was a significant correlation between FEV₁ and PC₂₀ salbutamol ( r  = 0.815, P  < 0.001).
Conclusions:   These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.     

Bronchial Sensitivity to Histamine in Former Asthmatics: Redevelopment of Symptoms During a Year of Followup

The aim of this protocol was to study bronchial responsiveness in 23 former asthmatics who were free of symptoms for at least 5 years. Bronchial hyperreactivity (BHR) was evaluated with histamine challenge test and the results were compared with those of 20 normal subjects and 20 current asthmatic patients. Among the former asthmatics 65% fulfilled the criteria of BHR. During 1 year of followup, two former asthmatics redeveloped asthma symptoms. Interestingly, one patient had no BHR when initially tested. These findings suggest that the absence of BHR does not guarantee the nonrecurrence of asthma symptoms in former asthmatics.     

The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airway hyperresponsiveness

In healthy subjects, deep inspiration (DI) acts both as a bronchodilator and a bronchoprotector. The latter is impaired in asthmatics. We have now evaluated whether the lack of bronchoprotection is related to bronchial hyperresponsiveness (BHR), and whether the bronchodilatory effect is also lost in asthmatics. Ten healthy subjects (PC20 > 75 mg/ml), 12 asthmatics with moderate to severe BHR (PC20 < 1 mg/ml), 14 asthmatics with mild to borderline BHR (1 < PC20 < 25 mg/ml), and 10 rhinitics with mild to borderline BHR (1 < PC20 < 25 mg/ml) underwent single-dose methacholine provocations inducing at least 20% reduction in FEV1 after 20 min of DI inhibition. To measure the bronchodilatory effect, DIs were taken immediately after the postmethacholine spirometry, and lung function was again tested. To measure the bronchoprotective effect, DIs were taken before the administration of spasmogen. All four groups achieved the same reductions in FEV1 and FVC, in the absence of deep breaths (analysis of variance [ANOVA], p = 0.49). Only healthy subjects showed bronchoprotection (percent bronchoprotection, mean +/- SEM; healthy: 79 +/- 4.0; asthmatics with moderate to severe BHR: 12 +/- 14.5; asthmatics with mild to borderline BHR: -7 +/- 19.7; rhinitics with mild to borderline BHR: 2 +/- 14.0). In contrast, DIs were able to partially reverse bronchial obstruction in all four groups, albeit percent bronchodilation in healthy subjects was somewhat stronger. The dissociation between bronchoprotection and bronchodilation suggests that the two effects involve different mechanisms.     

Contribution of Impedance Measurement of the Respiratory System to Bronchial Challenge Tests

The contribution of impedance measurement of the respiratory system to bronchial challenge tests was studied in 64 asthmatics and 23 control subjects.

After histamine challenge, resistance values increased significantly at all frequencies but most markedly at the lower frequencies in the asthmatic group; reactance values significantly decreased at all frequencies. In the control group, resistance significantly increased at 8 and 12 Hz. However, reactance decreased significantly at all frequencies.

By multiple logistic model analysis, a simple discriminant score was found with great discriminating power to differentiate asthmatics and nonasthmatics. The discriminating score equals 9 x FEV_{1 aft} - 7 x FEV_1bef

Adding the forced oscillation technique to the equipment for measuring the bronchial response after challenging procedures can give information about the localization of the response to the challenge in the respiratory system.     

P—选择素在速激肽类致气道高反应性中的作用

目的 探讨黏附分子Ｐ－选择素和速激肽类Ｐ－物质、血管活性肠肽（ＶＩＰ）与气道高反应性的关系。方法 测定５７例支气管哮喘病人（激素治疗组２７例,非激素治疗组３０例）和２２例正常人的气道反应性,观察血浆Ｐ－选择素、Ｐ－物质和ＶＩＰ的变化。结果５３例哮喘病人气道激发试验阳性（９２．９８％）,４例阴性（７．０２％）,２２例正常人全部阴性。非激素治疗组患者血浆Ｐ－选择素和Ｐ－物质较正常人及激素治疗组显著升     

Exhaled Nitric Oxide as a Simple Assessment of Airway Hyperresponsiveness in Bronchial Asthma and Chronic Cough Patients

Exhaled nitric oxide (NO) has been suggested to be a marker of airway inflammation. The aim of this study was to evaluate the role of exhaled NO in bronchial asthma and chronic cough patients to predict bronchial hyperresponsiveness (BHR). We measured the exhaled NO concentration using the chemiluminescence method in 52 asthma patients (group I consisting of 24 without prior inhaled corticosteroid (ICS) use, and group II consisting of 28 previously on ICS and 16 chronic cough patients in group III). In addition to regular examinations, spirometry and methacholine inhalation tests using the Astograph were done. In group I, a significantly negative correlation was observed regarding the exhaled NO concentration with FEV₁/FVC%, V₅₀, and BHR that was assessed as Dmin and PD₃₅-Grs, and a positive correlation with peripheral blood eosinophils. In group III, a significantly negative correlation was seen regarding the exhaled NO concentration with BHR. We thus concluded that measuring exhaled NO concentration appears to be a useful noninvasive method to predict the BHR, airway obstruction, and inflammation in asthma and chronic cough patients.     

Relation of Airway Reactivity and Sensitivity with Bronchial Pathology in Asthma

Airway hyperresponsiveness in asthmatics, which may result from inflammation or remodeling, is expressed as the concentration of methacholine that causes a 20% fall in FEV₁ in the concentration-response curve (PC₂₀). A decrease in PC₂₀ may be due to a steeper curve (hyperreactivity) and/or a curve shift to the left (hypersensitivity). Our purpose was to analyze the relation of airway sensitivity and reactivity to airway pathological changes. The PC₆, as sensitivity parameter, and the slope between PC₂₀ and PC₄₀ as reactivity parameter, were calculated. Total and differential cell counts in the bronchoalveolar lavage fluid, and percentage of epithelial shedding, basement membrane thickness, and submucosal thickness on bronchial biopsy, were measured. The PC₆ showed a correlation with the baseline FEV₁%. The slope was significantly correlated with the basement membrane thickness, and also demonstrated a strong association with submucosal thickness. The PC₂₀ showed a correlation with the baseline FEV₁% and the degree of epithelial shedding. These results suggest that the airway sensitivity and reactivity measurements reflect the degree of airway caliber and remodeling, respectively.     

Low-Attenuation Areas of the Lungs on High-Resolution Computed Tomography in Asthma

To investigate the low-attenuation areas of the lungs (LAA) in asthma, we compared the mean lung density (MLD) and the LAA in 22 asthmatics (12 ex-smokers and 10 nonsmokers) and 13 patients with chronic obstructive pulmonary disease (COPD) by high-resolution computed tomography. The MLD and the relative area of the lung with attenuation values lower than -950 Hounsfield Units at full inspiration (inspiratory RA₉₅₀) were significantly different in nonsmoking asthmatics compared to patients with COPD and asthmatics with a smoking history. The MLD and the RA₉₅₀ correlated significantly with the FEV₁ in all groups and with the DL_CO in patients with COPD and asthmatics with a smoking history but not in nonsmoking asthmatics. We concluded that the LAA in asthmatics with a smoking history indicates the presence of emphysema, but in nonsmoking asthmatics it reflects hyperinflation and nonemphysematous expiratory airflow limitation rather than emphysematous lesions.     

Postural Changes in Nasal and Pulmonary Resistance in Subjects with Asthma

Introduction. Subjects with asthma frequently have nasal symptoms and complain of orthopnoea but airflow resistance is usually only assessed during oral breathing and while seated. Method. We have used a forced oscillation technique to measure total respiratory resistance (Rrs) at 6Hz during mouth breathing (Rrs,mo) and during nose breathing (Rrs,na) in the sitting and supine postures; resistance of the nasal airway (Rnaw) was estimated as Rrs,na - Rrs,mo. Forced oscillations were applied during normal tidal breathing and the mid-tidal lung volume (MTLV) was determined for each breathing route and posture. Subjects. Three groups of subjects were studied: 10 normal subjects without lung or nasal disease (N; five males, mean age 33.5 [range 23-58] years, mean FEV₁ 105%pred, FEV₁/VC 86%); seven subjects with asthma alone (A; four males, 40.3 [23-57] years, mean FEV₁ 66%pred, FEV₁/VC 74%); 10 asthmatic subjects with nasal obstructive symptoms (AN; six males, 62.8 [38-80] years, mean FEV₁ 56%pred, FEV₁/VC 75%). Results. In all three groups of subjects, mean Rrs,mo and Rrs,na were higher in the supine than sitting posture. In normal subjects the increase in supine Rrs,mo was associated with a 0.6 liter fall in MTLV. In asthma supine Rrs,mo increased despite a much smaller fall in MTLV; supine increases in Rrs,na were particularly large in presence of nasal disease. Discussion. Values of airflow resistance are 2-3 times higher in both normal and asthmatic subjects when breathing via the nose and supine than under normal laboratory conditions of oral breathing and seated.     

Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis.

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma which is often associated with airways inflammation. However, some patients with allergic rhinitis and no clinical evidence of asthma also exhibit BHR. This study therefore investigated whether inflammatory cell infiltrate is present in the induced sputum of nonasthmatic subjects with allergic rhinitis during the pollen season and examined its relationship with airway hyperresponsiveness to inhaled methacholine and adenosine 5'-monophosphate (AMP). Twenty subjects (12 allergic rhinitis, eight nonallergic controls) underwent methacholine and AMP challenge and sputum induction with hypertonic saline on separate days. Cell differentials were calculated from whole sputum samples. A significantly greater number of eosinophils was found in the sputum of nonasthmatic subjects with allergic rhinitis compared to that of nonallergic controls, their median (range) percentages being 17.5 (4-47) and 1.5 (0-5) (p<0.001) respectively. Although sputum eosinophilia failed to be significantly associated with methacholine responsiveness (r(s)=-0.50; p=0.095), the provocative concentration of AMP causing a 20% fall in forced expiratory volume in one second correlated strongly and significantly with the absolute number of eosinophils (r(s)= -0.73; p=0.007). Eosinophil cationic protein levels in the sputum of rhinitic subjects were significantly elevated compared to controls and correlated with eosinophil number (r(s)=0.67; p=0.017). These findings support the view that bronchial eosinophilia alone is insufficient to cause asthmatic symptoms. Diverse agonists for assessing bronchial hyperresponsiveness are selectively associated with airway inflammation in allergic rhinitis.     

Understanding How Asthmatics Perceive Symptom Distress During a Methacholine Challenge

The way, or ways, in which asthmatics recognize specific symptom(s) with varying degrees of their airway obstruction, or asthma severity, is poorly understood. Our purpose was to gain a better understanding of how asthma patients during acute episodes, based on their symptom perception, decide when to seek symptom relief. A cross-sectional design was used to study 32, 16 per group, African Americans and Caucasians with a mean age of 34.5 years. All had mild, stable asthma (FEV₁ ≥70%), were non-smokers, atopic, and had not used inhaled or oral steroids for 3 months. Their mean baseline FEV₁ was 97.5% predicted; all were controlled with intermittent use of a beta agonist inhaler. All had a bronchoconstrictor challenge using a provocative concentration of methacholine to achieve a 30% fall (PC30) in their FEV₁. After achieving a PC30 and before their first dose of a bronchodilator was given, all subjects were asked: “If you felt this way at home would you take your inhaler?” Subjects were blinded to the fact that the yes/no question was asked when their FEV₁ was reduced by 30%. In both groups, 44% responded “no” that they would not use their inhaler at that point in time. This finding suggests that those subjects, the 44% who failed to associate a change in their symptoms with increased airflow obstruction, may be at risk for life-threatening episodes.     

雾化吸入沙丁胺醇联合无创机械通气治疗慢性阻塞性肺疾病急性发作的临床分析

目的探讨雾化吸入沙丁胺醇联合无创机械通气治疗方案对慢性阻塞性肺疾病急性发作(AECOPD)患者支气管舒张反应、气体交换参数的影响。 方法选取我院80例(AECOPD)患者,随机分为2组,对照组38例,实验组42例,对照组采用无创机械通气疗法,实验组于其基础上雾化吸入沙丁胺醇,比较2组治疗前后肺功能[用力肺活量(FVC)、1 s用力呼气量(FEV₁)、FEV₁/FVC]、气体交换参数[每分钟通气量(VE)、潮气量(VT)、呼吸频率(RR)]、支气管舒张试验反应[FVC改变量(ΔFVC)与改善率、FEV₁改变量(ΔFEV1)与改善率]、症状与体征消失时间及不良反应情况。 结果实验组治疗后FVC、FEV₁、FEV₁/FVC显著高于对照组(P<0.05);实验组治疗后VE、VT、RR显著高于对照组(P<0.05);2组ΔFEV1与改善率比较无显著差异(P>0.05),实验组ΔFVC与改善率明显小于对照组(P<0.05);实验组咳嗽、喘憋、发绀、肺啰音消失时间明显短于对照组(P<0.05);2组不良反应总发生率比较无显著差异(P>0.05)。 结论雾化吸入沙丁胺醇联合无创机械通气可有效改善AECOPD患者肺功能与气体交换参数,降低支气管舒张试验反应,促进症状与体征恢复,且安全性高。     

Asthma Control in a Random Sample of New Zealand Adolescent Asthmatics

Asthma control, defined by asthma symptoms and lung function, and asthma medication use, was assessed in 123 adolescent asthmatics. Sputum eosinophilia (≥ 2.5% eosinophils) and bronchial hyperresponsiveness (BHR) to hypertonic saline were also measured to assess whether these additional objective parameters might aid in determining asthma control; 54.5% of subjects had adequately controlled asthma; 50.4% of all subjects reported inhaled corticosteroid use in the preceding 12 months; however, only 22.3% reported regular use. Although BHR and median eosinophil numbers were significantly higher in the inadequately controlled asthmatics, BHR and sputum eosinophilia had poor sensitivity for detecting inadequate asthma control.