Methacholine-induced fall in forced vital capacity as a marker of asthma severity.

The dose of methacholine causing a 20% fall in forced expiratory volume in 1 sec (FEV1) from baseline (PD20) has been used as an index of asthma severity. The aim of this study was to determine if the percentage fall in forced vital capacity (FVC) from baseline at the PD20 (dFVC%) is an independent marker of asthma severity. We first retrospectively studied the dFVC% and PD20 obtained from 149 consecutive newly diagnosed asthmatics with a positive methacholine-challenge test (MCT). We then performed MCT on 20 normal subjects and 35 stable asthmatics. The 'milder' asthmatics (n = 20) and 'more severe' asthmatics (n = 15) were on regular inhaled corticosteroids: 200 micrograms or less and 800 micrograms or more daily, respectively. A dosimeter technique was used, and normal subjects were given a cumulative dose of 2400 micrograms. The PD20 and dFVC% were calculated using log-linear interpolation of the last two points. Student's unpaired t-tests and linear regression analyses were used for comparison and correlation of results. There was no significant correlation between dFVC% and PD20 among the 149 newly diagnosed asthmatics (r = 0.1), or among the 35 known stable asthmatics (r = 0.008). The more severe asthmatics had a larger dFVC% compared with the milder asthmatics (15.8% vs. 9.6%; P = 0.0005). In addition, inhaled corticosteroid usage correlated better with dFVC% (r = 0.56) than with PD20 (r = 0.36). The normal subjects had a mean fall in FVC of only 4.8%. The percentage fall in FVC at PD20 (dFVC%) may be a useful index of asthma severity which is independent of PD20. This index is potentially complementary to the PD20 in the assessment of asthma severity.     

PC(20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine

Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5'-monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV(1) to drop by 20% (PC(20)) is more closely associated with inflammatory parameters in asthma than PC(20) methacholine. In 120 patients with atopic asthma (median FEV(1) 81% predicted [pred], median age 27 yr), PC(20) methacholine and PC(20) AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC(20) methacholine was predominantly predicted by FEV(1) %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC(20) AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV(1) %pred was only an additional independent predictor (total ev = 36%). PC(20) AMP reflects more closely the extent of airway inflammation due to asthma than PC(20) methacholine.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

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.     

Exploring the relationship between forced maximal flow at functional residual capacity and parameters of forced expiration from raised lung volume in healthy infants

The raised volume rapid thoraco-abdominal compression technique (RVRTC) is being increasingly used to assess airway function in infants, but as yet no consensus exists regarding the equipment, methods, or analysis of recorded data. The aim of this study was to explore the relationship between maximal flow at functional residual capacity (V'(maxFRC)) and parameters derived from raised lung volumes, and to address analytical aspects of the latter technique in an attempt to assist with future standardization initiatives. Forced vital capacity (FVC) from lung volume raised to 3 kPa, timed forced expiratory volumes (FEV(t)), and forced expiratory flow parameters at different percentages of expired FVC (FEF(%)) were measured in 98 healthy infants (1-69 weeks of age). V'(maxFRC) using the tidal rapid thoraco-abdominal compression (RTC) technique was also measured. The within-subject relationships and within-subject variability of the various parameters were assessed.Duration of forced expiration was < 0.5 sec in 5 infants, meaning that FEV(0.3) and FEV(0.4) were the only timed volume parameters that could be calculated in all infants during the first months of life, and even when it could be calculated, FEV(0.5) approached FVC in many of these infants. It is recommended that FEV(0.4) be routinely reported in infants less than 3 months of age. Contrary to previous reports, within subject variability of V'(maxFRC) was less than that of FEF(75) (mean CV = 6.3% and 8.9%, respectively).A more standardized protocol when analyzing data from the RVRTC would facilitate comparisons of results between centers in the future.     

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.     

Corticosteroid-induced improvement in the PC20 of adenosine monophosphate is more closely associated with reduction in airway inflammation than improvement in the PC20 of methacholine.

It has been suggested in cross-sectional studies that provocation with adenosine 5'-monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antiinflammatory therapy.     

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.     

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.     

The relationship between diuretic dose, and the haemodynamic response to captopril in patients with cardiac failure.

The effect of diuretic dose on the haemodynamic response to captopril was assessed in nine patients with chronic cardiac failure. Each patient was given an intravenous dose of captopril while maintained on (a) a low dose diuretic regime, and (b) a high dose diuretic regime. Activity of the renin angiotensin aldosterone system, as assessed by plasma concentrations of these hormones, was greater when patients were receiving the higher dose diuretic regime. The magnitude of haemodynamic response produced by intravenous captopril was greater when the patients were maintained on the high dose diuretic regime, although no significant correlation was found between resting plasma renin activity and resting plasma angiotensin II concentration and the change produced by captopril in any haemodynamic response on either diuretic regime. An increased dosage of loop diuretic potentiates the haemodynamic effects of captopril in patients with cardiac failure. Reduction of diuretic dose prior to introduction of captopril may protect against severe first dose hypotension.     

深吸气量与稳定期慢性阻塞性肺病患者运动耐力的相关性研究

目的探讨深吸气量（IC）与稳定期慢性阻塞性肺病患者（COPD）运动耐力的相关性。方法对人选的30例稳定期COPD患者,每日吸入噻托溴胺粉雾剂18ug,连续观察12周。于第1、43、85天检查呼吸困难的评分,6分钟行走距离（6MWD）,一秒钟用力呼气量（FEV1）,用力肺活量（FVC）,深吸气量（IC）等指标,比较用药前后各变量变化的统计学意义及肺功能各变量与6MWD的相关性。结果用药后FEV1和FEV1／FVC均有所改善,其中FEV1的改善要好于FEV1／FVC改善,但与用药前比较,均无显著差异（P〉0．05）;用药后6周、12周IC较用药前比较有显著增加（t=4．596、5．405,P均〈0．01）,6MWD用药后6周、12周较用药前有显著提高（t=4．628、6．207,P均〈0．01）;用药后6周、12周呼吸困难评分的下降较用药前比较有显著差异（z=4．433、4．026,P均〈0．001）;回归分析显示IC的变化与6MWD的变化均有较好的相关性（r=0．900、0．873,P均〈0．01）。结论本研究的结果提示比较其他肺功能指标,伦的改变与呼吸困难和运动耐力的改变有更好地相关性,IC的测定有助于COPD患者治疗效果及生活质量的预测。     

Evaluation of a hand-held spirometer, the Respiradyne, for the measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR)

A hand-held spirometer, the Respiradyne (R), was evaluated for the measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) by comparing it with a Vitalograph spirometer (V) and a Wright's peak flow meter (W) in 70 subjects (normals and patients). The results showed close agreement for FEV1; r = 0.99, R = 0.961V + 0.03 X 10(-5) and FVC; r = 0.99, R = 1.003V-0.044. Results for PEFR using the Respiradyne were generally higher than with the peak flow meter; r = 0.98, R = 1.151W-17.576. The Respiradyne is portable and simple to operate and may be suited to use in a variety of non-laboratory situations.     

The relationship between functional capacity (FC) and cardiovascular risk factors (CVRFs) in senile patients after noncardiac surgery

The aim of the present study was to investigate the relationship between the number of cardiovascular risk factors (CVRFs) and functional capacity (FC) in the senile patients undergone noncardiac surgery. One hundred and eighty-two senile patients scheduled for elective noncardiac surgery were selected. According to the Duke activity status index (DASI), the FC of each patient was evaluated, and also their CVRFs were recorded. According to the number of CVRFs, the patients were ranked into different groups. The significant differences in FC between the groups^’ were identified using the analysis of variance. The examination showed that FC decreased with the increasing number of CVRFs. As a conclusion, we emphasize that with the increasing number of CVRFs, the FC of senile patients, i.e., their metabolic equivalents (METs) decrease. The occurrence of low FC and higher CVRFs is a common phenomenon in senile patients.     

OSAHS患者咽部解剖与呼吸驱动的关系研究

目的 探讨OSAHS患者咽腔形态与呼吸驱动(p0.1)的关系.方法 随机选取OSAHS患者35例,进行仰卧位睡眠状态下呼吸驱动测定及螺旋CT扫描,针对轻度(AHI ＜20)、中重度(AHI＞ 20)两组患者进行研究.结果 睡眠状态下,①中重度组软腭长度,软腭厚度,颏舌肌宽度及舌体面积明显增加(P＜0.05),软腭后区最小气道面积明显减小(P＜0.05);②中重度组P0.1的下降更为明显(P＜0.05).③中重度组颏舌肌宽度与P0.1有明显负相关性(r=-0.574,P＜0.05).结论 睡眠状态下,咽腔狭窄程度与OSAHS病情相关,随着OSAHS患者病情加重,颏舌肌的代偿作用增加,当代偿到一定程度时出现呼吸驱动的降低.     

The relationship between functional capacity (FC) and cardiac autonomic nervous dysfunction to surgery stress in senile patients

The aim of the study presented here is to compare the pre- and post-operative cardiac autonomic nervous function of senile patients with different functional capacities (FC). Ninety-two senile patients scheduled for elective non-cardiac surgery were selected, whose FC was evaluated in terms of Duke activity status index (DASI). According to FC, the patients were classified into three groups: Group 1 (poor FC); Group 2 (moderate FC) and Group 3 (excellent FC). Heart rate variability (HRV) was monitored during the night before, on the 1st and the 2nd day after operation respectively. The results demonstrated some indices of pre-operative HRV of patients with poor or moderate FC were significantly lower than those with excellent FC. After surgery, total power (TP), high frequency (HF), low frequency (LF) and very low frequency (VLF) of all patients were significantly decreased. The LF/HF of patients with a poor or moderate FC showed a significant difference compared to patients with excellent FC. In conclusion, we emphasize that surgery induced a cardiac autonomic nervous dysfunction in senile patients not only with low FC but also with high FC; the disturbance of pre- and post-operative cardiac autonomic nervous activity is associated with a diminished FC (<7METs = metabolic equivalents) in senile patients.