Pulmonary function characteristics in patients with different patterns of methacholine airway hyperresponsiveness

STUDY OBJECTIVES: The American Thoracic Society guidelines for methacholine-induced airway hyperresponsiveness include a > or = 20% reduction in FEV(1) or a > or = 40% reduction in specific airway conductance (sGaw). The objectives of the current study are to assess the concordance between these two criteria and to characterize the pulmonary function and respiratory symptoms of patients with different patterns of methacholine hyperresponsiveness. STUDY DESIGN: A prospective study of 248 consecutive patients referred for methacholine bronchoprovocation testing. RESULTS: Positive methacholine hyperresponsiveness was noted in 179 patients; 139 patients (78%) had a > or = 20% reduction in FEV(1), whereas 40 patients (22%) had a > or = 40% reduction in sGaw alone without a significant change in FEV(1). The former group had the following: (1) higher baseline lung volumes, (2) lower baseline values of FEV(1) and sGaw, (3) forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75))/FVC ratios compared to patients with a reduction in sGaw alone (0.72 +/- 0.26 vs 0.97 +/- 0.28, mean +/- SD; p < 0.0001), and (4) more frequent presence of wheezing and chest tightness (p < 0.05). CONCLUSIONS: First, a substantial number of patients have a reduction in SGaw alone in response to methacholine, and secondly, this response is seen in patients with a higher FEF(25-75)/FVC ratio. Since the FEF(25-75)/FVC ratio is thought to be an index of airway size relative to lung size, we speculate that the larger intrinsic airway size relative to lung size may explain the differences in baseline parameters and patterns of methacholine hyperresponsiveness.     

呼气相气道内负压法检测呼气流速受限应用于儿童支气管激发试验的可行性

目的 观察支气管哮喘(简称哮喘)患儿支气管组胺激发试验前、后呼气流速受限(EFL)情况,并与常规的以第1秒用力呼气容积(FEV1)作为判断指标的支气管激发试验结果进行比较,探讨EFL作为支气管激发试验判断指标的可行性.方法 非急性发作期哮喘30例患儿,采用呼气相气道内负压(NEP)法检测患儿支气管组胺激发试验前、后EFL情况.结果 30例非急性发作期哮喘息儿中,支气管组胺激发试验阳性者(BPT阳性组)19例,阴性者(BPT阴性组)11例.BPT阳性患儿激发前、后FEV1分别为(1.71±0.52)L和(1.21±0.34)L,FEV1下降率为(29.04±7.49)%,19例BPT阳性患儿激发前和激发后分别有1例和3例出现卧位EFL,坐位时均无EFL,患儿3分法EFL和5分法EFL激发前(分别为1.05±0.23和0.05±0.22)与激发后(分别为1.16±0.37和0.26±0.65)比较差异均无统计学意义(t分别为1.455和1.714,P分别为0.163和0.104).BPT阴性患儿激发前、后FEV1分别为(1.89±0.80)L和(1.79±0.78)L,FEV1下降率为(6.09±5.29)%,11例BPT阴性患儿激发前与激发后均无EFL.结论 NEP法检测EFL不能敏感反映传统支气管激发试验阳性判断标准(FEV1下降≥20%)的变化,其在支气管激发试验中的可行性和阳性判断标准尚有待进一步研究探讨.     

呼气相气道内负压法检测呼气流速受限应用于儿童支气管激发试验的可行性

目的观察支气管哮喘（简称哮喘）患儿支气管组胺激发试验前、后呼气流速受限（EFL）情况,并与常规的以第1秒用力呼气容积（FEV1）作为判断指标的支气管激发试验结果进行比较,探讨EFL作为支气管激发试验判断指标的可行性。方法非急性发作期哮喘30例患儿,采用呼气相气道内负压（NEP）法检测患儿支气管组胺激发试验前、后EFL情况。结果30例非急性发作期哮喘患儿中,支气管组胺激发试验阳性者（BPT阳性组）19例,阴性者（BPT阴性组）11例。BPT阳性患儿激发前、后FEV1分别为（1．71±0．52）L和（1．21±0．34）L,FEV1pred％下降率为（29．04±7．49）％,19例BPT阳性患儿激发前和激发后分别有1例和3例出现卧位EFL,坐位时均无EFL,患儿3分法EFL和5分法EFL激发前（分别为1．05±0．23和0．05±0．22）与激发后（分别为1．16±0．37和0．26±0．65）比较差异均无统计学意义（t分别为1．455和1．714,P分别为0．163和0．104）。BPT阴性患儿激发前、后FEV1分别为（1．89±0．80）L和（1．79±0．78）L,FEV1pred％下降率为（6．09±5．29）％,11例BPT阴性患儿激发前与激发后均无EFL。结论NEP法检测EFL不能敏感反映传统支气管激发试验阳性判断标准（FEV1pred％下降≥20％）的变化,其在支气管激发试验中的可行性和阳性判断标准尚有待进一步研究探讨。     

Airway challenge testing - accuracy of the interrupter technique

According to national and international recommendations the bronchial sensitivity should be determined based on the decrease of the FEV1 by 20 % (FEV1 - 20) or the increase of the airway resistance by means of body plethysmography by 100 % (Raw + 100). Measurement of airway resistance by interrupter technique (Rint) is a simple method and needs no active cooperation of the patient, but is not recommended in airway challenge testing. We investigated the role of the increase of Rint by 100 % (Rint + 100) compared to Raw + 100 and FEV1 - 20 during carbachol airway challenge testing by means of dosimetry. We examined 123 patients with following symptoms: 85 x coughing, 31 x coughing and dyspnea, 7 x medical opinion. Significant correlations between Rint and Raw were found before and after the challenge tests (Rint before/after 0,3 +/- 0,13/0,36 +/- 0,25 kPa*s/l; Raw before/after 0,24 +/- 0,09/0,50 +/- 0,41 kPa*s/l; r = 0,504/0,672; p < 0,001 [Pearson]). The median values of Rint and Raw were significantly different (p < 0,001 [Wilcoxon]). Moreover Rint systematically overestimated airway resistance in the normal range and underestimated the increase of airway resistance during challenge testing (r = 0,783; p < 0,001 [Pearson]). In 58 patients an increased airway responsiveness was found. In 21 oft these patients there was no increase of Rint above the initial value. Sensitivity/specificity/positive predictive value/negative predictive value in % to the detection of airway hyperresponsiveness were in Rint + 100 9/95/63/54, in FEV1 - 20 61/100/100/66 and in Raw + 100 98/100/100/98. In conclusion we found significant correlations between Rint and Raw, but the median values were systematically and significantly different. Rint + 100 had a low sensitivity to detect airway hyperresponsiveness and is not comparable with FEV1 - 20 or Raw + 100.     

Ratio between forced expiratory flow between 25% and 75% of vital capacity and FVC is a determinant of airway reactivity and sensitivity to methacholine

STUDY OBJECTIVE: The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF(25-75)/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages. STUDY DESIGN: Data analysis of consecutive subjects who had a >or= 20% reduction in FEV(1) after 相似文献   

Does negative expiratory pressure influence performances of spirometry in older patients?

The aim of this study is to assess the influence of the negative expiratory pressure (NEP) technique on the performance of maximal expiratory manoeuvre in elderly patients. Firstly, the authors studied how NEP (at 5 and 10 cmH2O, NEP5 and NEP10) influences forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 60 young healthy volunteers, in order to assess the fluctuations of the method. In the second part of the study, 65 successive elderly inpatients (>70 yrs old) were examined. In this group, 15 elderly patients were unable to perform the manoeuvre, 27 had a normal function, 14 had a lung function with obstructive pattern and nine with restrictive pattern. In young subjects, FVC during NEP5 and NEP10 compared to baseline values was 101+/-5%, and 103+/-5%, respectively, and FEV1 was 100+/-4% and 101+/-5%, respectively. In elderly patients with normal function, FVC during NEP5 and NEP10 compared to baseline values was 99+/-14% and 109+/-23%, respectively, and FEV1 was 97+/-9% and 104+/-13%, respectively. There were no relevant effects of the NEP application on FVC or FEV1 values in elderly patients with an obstructive or restrictive pattern. In elderly patients, the use of the negative expiratory pressure technique during maximal expiratory manoeuvres provides little complementary information compared to a classical manoeuvre. The negative expiratory pressure technique did not modify the initial diagnosis when compared with the classical manoeuvre.     

Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography

The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P < 0.001); respective relationships for change after bronchodilator were r = 0.09 (ns) and r = 0.64 (P < 0.001). FEF50 also correlated significantly with Rint (R = 0.769, P < 0.001) but not with T(PTEF)/T(E). FEV1 and FEF50 both increased postbronchodilator, with respective mean changes of 11.4% and 28% (P < 0.001), while Rint decreased by 24.3% (P < 0.001). No significant changes were noted for T(PTEF)/T(E). T(PTEF)/T(E) derived from inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.     

Changes in airway responsiveness following mantle radiotherapy for Hodgkin's disease

STUDY OBJECTIVES To investigate whether mantle radiotherapy (MRT) for the lung, through its proinflammatory effects, can induce an increase in airway responsiveness. DESIGN: Follow-up of the changes in lung function and methacholine responsiveness in patients 1, 6, 12, and 24 months after they underwent MRT. PATIENTS: Thirteen nonasthmatic patients with bulky Hodgkin's lymphoma who were scheduled for MRT. MEASUREMENTS AND RESULTS: Chest radiographs, lung function tests, methacholine thresholds of the bronchi (the provocative dose of methacholine causing a 10% fall in FEV(1) [PD(10)]) and central airway (the provocative dose of methacholine causing a 25% fall in the maximal mid-inspiratory flow [PD(25)MIF(50)]), and the provocative dose of methacholine causing five or more coughs (PDcough) were serially assessed. One month after patients underwent MRT, there were significant decreases in PD(10) (mean [+/- SEM], 2,583 +/- 414 microg to 1,512 +/- 422 microg, respectively; p < 0.05), PD(25)MIF(50) (mean 2,898 +/- 372 microg to 1,340 +/- 356 microg, respectively; p < 0.05), and PDcough (mean 3,127 +/- 415 microg to 1,751 +/- 447 microg; p < 0.05), which were independent of the decrease in FEV(1) and reversed within 6 months in all patients but three. Six months after undergoing MRT, four patients showed radiation-induced lung injury (RI) on chest radiographs, which subsequently evolved into fibrosis. These patients had greater decreases in vital capacity, FEV(1), MIF(50), and methacholine thresholds than those without RI, and this persisted up to 2 years after they had undergone MRT. One year after the patients underwent MRT, a close relationship was found overall between the change in FEV(1) and those in both PD(10) (r = 0.733; p = 0.004) and PD(25)MIF(50) (r = 0.712; p = 0.006). CONCLUSIONS:: MRT triggers an early transient increase in airway responsiveness, which reverses spontaneously. In patients with RI, the persistence of airway dysfunction long after undergoing MRT may depend on airway remodeling from radiation fibrosis.     

Regular inhaled salbutamol : effect on airway responsiveness to methacholine and adenosine 5'-monophosphate and tolerance to bronchoprotection

OBJECTIVE: Regular treatment with inhaled beta(2)-agonists increases airway responsiveness consistently to indirect bronchoconstrictors (allergen, exercise, hypertonic saline solution, etc) and inconsistently to direct bronchoconstrictors (histamine, methacholine). Studies demonstrating tolerance to beta(2)-agonist bronchoprotection against the indirect bronchoconstrictor adenosine 5'-monophosphate (AMP) have not examined changes in baseline AMP responsiveness. This study assessed the effect of regular salbutamol on AMP and methacholine responsiveness and on tolerance to bronchoprotection. DESIGN: Double-blind, randomized, crossover study. SETTING: University hospital bronchoprovocation laboratory. PATIENTS: Fourteen atopic asthmatic subjects with FEV(1) > 65% predicted, and methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)) < 8 mg/mL. INTERVENTIONS: Salbutamol, 100 microg, and placebo inhalers, two puffs qid, each for 10 days. MEASUREMENTS: Methacholine PC(20) and AMP PC(20) measured 12 h after blinded inhaler after each treatment period. Methacholine PC(20) and AMP PC(20) repeated 10 min after salbutamol, 200 microg (eight subjects). RESULTS: There was no difference between placebo and salbutamol treatment in geometric mean methacholine PC(20) (0.85 mg/mL vs 0.82 mg/mL, p = 0.86) or AMP PC(20) (22 mg/mL vs 17.4 mg/mL, p = 0.21; n = 14). The acute bronchoprotective effect of salbutamol was greater vs. AMP than vs methacholine (5.1 doubling concentrations vs. 3.5 doubling concentrations, p = 0.06) and loss of protective effect of salbutamol (mean +/- SD) was greater vs AMP than vs. methacholine (2.4 +/- 0.33 doubling concentration loss vs 0.8 +/- 0.21 doubling concentration loss, p = 0.008; n = 8). CONCLUSION: Regular salbutamol (mean +/- SD) treatment did not enhance airway responsiveness to either the indirect bronchoconstrictor AMP or the direct bronchoconstrictor methacholine. Compared to its effect on methacholine, salbutamol had a greater acute protective effect vs AMP and produced greater loss of protection vs AMP when used regularly.     

Maximal airway response to methacholine in cough-variant asthma: comparison with classic asthma and its relationship to peak expiratory flow variability

BACKGROUND: In asthmatic subjects, not only airway sensitivity but maximal airway response are increased on the dose-response curve to methacholine, and peak expiratory flow (PEF) variability is closely related to airway hypersensitivity and maximal airway response. OBJECTIVE: The aims of this study were to compare the prevalence and the level of maximal response plateau between patients with cough-variant asthma (CVA) and those with classic asthma (CA), and to examine the relationship between airway hypersensitivity or maximal airway response and PEF variability in patients with CVA. METHODS: A high-dose methacholine inhalation test was performed on 83 patients with CVA and on 83 patients with CA matched for provocative concentration of methacholine causing a 20% fall in FEV1 (PC20). PEF was recorded in the morning and evening for 14 consecutive days in 78 CVA patients, and the amplitude percentage mean was used to express the diurnal PEF variation. RESULTS: Fifty-two CVA subjects (62.7%) but only 33 CA subjects (39.8%) showed a maximal response plateau. This difference was significant after correction by the Bonferroni method (corrected p = 0.024). Subjects in the CVA and CA groups showing a plateau had significantly different plateau levels (38.0 +/- 5.9% vs 42.9 +/- 3.9%, corrected p = 1.0 x 10(-4)). In patients with CVA, no significant relationship was found between PC20 and PEF variability. However, the absence of a maximal response plateau and a higher plateau level were associated with increased PEF variability. CONCLUSIONS: Maximal airway response may be an important confounder in the relationship between airway hypersensitivity and the clinical expression of asthma. The identification of a maximal response plateau and the level of this plateau in patients with CVA provide information relevant to PEF variability.     

Dyspnea perception and reversibility of methacholine-induced unlimited airway narrowing in asthmatics.

The hypothesis was that asthmatics might experience impaired perception of dyspnea and salbutamol-induced reversibility during unlimited airway narrowing. A total of 38 asthmatics (18 to 59 years of age) were examined. All patients underwent the methacholine challenge test. According to the dose-response curve to methacholine, they were categorized as having either unlimited airway narrowing (UAN group) (n = 20) or response plateau (RP group) (n = 18). Reversibility of methacholine-induced bronchoconstriction was measured 20 minutes after the inhalation of 400 microg of salbutamol to compare postbronchodilator FEV1 with baseline FEV1. Dyspnea perception was evaluated using the Borg Scale to calculate a perception score at a 20% decrease in FEV1 (PS20) and the slope alpha of the regression line between the changes in Borg scores and the reduction in FEV1 as percentage of the baseline value. Subjects in the UAN group exhibited significantly lower PS20 compared with the RP group (1.45+/- 0.23 vs. 2.84 +/- 0.35, p = 0.002); the mean of the slope values was higher in the RP group than it was in the UAN group (0.150 +/- 0.015 vs. 0.095 +/- 0.006, p = 0.003). Salbutamol-induced reversibility was significantly lower in the UAN group (81 +/- 1.4 % of baseline FEV1) compared with patients from the RP group (91 +/- 1.1% of baseline FEV1; p < 0.001). In conclusion, asthmatics during methacholine-induced unlimited airway narrowing exhibit diminished perception of dyspnea and lower bronchial reversibility to the baseline 20 minutes after inhalation of salbutamol. This suggests that more careful monitoring of the lung function for timely recognition of asthma deteriorations and adequate bronchodilatory therapy during severe acute attacks should be recommended for such patients.     

Influence of airway calibre on the intrapulmonary dose and distribution of inhaled aerosol in normal and asthmatic subjects

We investigated the relationship between airway calibre and the dose and distribution of inhaled aerosol in ten normal and six asthmatic subjects. Subjects inhaled saline aerosol containing 99mTcO4 delivered from a nebulizer connected to a dosimeter, and the lung fields were scanned with a gamma-camera. Right lung dose (RLD) was calculated as percentage of total dose. Intrapulmonary distribution was measured as penetration index (PI) (peripheral zone counts/central zone counts). Asthmatics had a significantly lower PI than normal subjects and there was a linear relationship between PI and baseline specific airway conductance (sGaw, p less than 0.001), and forced expiratory volume in one second (FEV1, p less than 0.05). After bronchodilatation with salbutamol (delta sGaw 101 +/- 31%, mean +/- SEM), PI increased from 0.73 +/- 0.11 to 1.09 +/- 0.15 (p less than 0.05); after bronchoconstriction with methacholine (delta sGaw 62.6 +/- 2.9%), PI decreased from 1.42 +/- 0.24 to 1.06 +/- 0.22 (p less than 0.05). Changes of PI were correlated with changes in sGaw and FEV1 (n = 20, p less than 0.001) but changes of RLD and changes in airway calibre were not. The distribution of inhaled aerosol, but not the dose, is largely dependent on airway calibre. The differences in PI between normal and asthmatic subjects may at best be explained by the differences in central airway calibre.     

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.     

Effects of a beta2-agonist on airway hyperreactivity in subjects with cervical spinal cord injury.

STUDY OBJECTIVE: Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with a beta2-agonist attenuates airway hyperresponsiveness in these subjects. PARTICIPANTS: Subjects with chronic cervical SCI previously demonstrating airway hyperreactivity were challenged with methacholine (n = 9) or histamine (n = 16) alone and, on a separate day, 25 min following inhalation of nebulized metaproterenol sulfate. RESULTS: Inhalation of the beta2-agonist was associated with an increase in provocative concentration causing a 20% decrease in FEV1 (PC20) values (geometric mean) from 1.01+/-2.76 to 20.54+/-6.24 mg/mL for methacholine and from 2.29+/-2.26 to 19.82+/-5.93 mg/mL for histamine. No correlation was found between specific PC20 values for individual subjects and percentage improvement in FEV1 (liter) following inhalation of metaproterenol sulfate and between PC20 values and baseline FEV1 percent. CONCLUSION: These data, combined with findings that patients with chronic high cervical SCI experience increased breathlessness following exposure to exogenous agents, suggest that long-term prophylactic beta2-agonist therapy may reduce respiratory symptoms associated with airway hyperreactivity in these patients.     

Pulmonary gas exchange responses to histamine and methacholine challenges in mild asthma.

Histamine (HIST) produces greater changes in bronchial and pulmonary vasculature, and so may produce more gas exchange abnormalities, than methacholine (MTH) after inhalational challenge. The goals of this study were to compare the effects of HIST and MTH challenge on pulmonary gas exchange in patients with mild asthma at an equivalent degree of bronchoconstriction. Eleven patients were studied (mean+/-SEM age, 22+/-1 yr; forced expiratory volume in one second (FEV1), 91+/-5% pred) using a randomized, double-blind cross-over design. Respiratory system resistance (Rrs), arterial blood gases, and ventilation-perfusion distributions were measured before and after HIST/MTH challenges when cumulative doses caused a 30% fall in FEV1. Compared with baseline, HIST and MTH provoked similar moderate to severe increases in Rrs (p<0.005 each), and mild to moderate decreases in arterial oxygen tension (Pa,O2) due to ventilation-perfusion abnormalities (dispersion of pulmonary blood flow -log SDQ-, 0.40+/-0.03-0.71+/-0.08 and 0.47+/-0.04-0.89+/-0.06; normal values <0.60-0.65), respectively, similar to those shown in mild to moderate acute asthma, without differences between them. For the same degree of airflow obstruction, both histamine and methacholine bronchoprovocations induce, in patients with mild asthma, very similar disturbances in ventilation-perfusion distribution and respiratory system resistance, suggesting similar mechanisms of airway narrowing.     

Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome

We examined whether patients with irritable bowel syndrome have increased airway responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after inhalation of increasing concentrations of methacholine. Responses obtained in 11 IBS patients were compared with those obtained in 11 normal subjects and in 11 subjects with organic disease of the gut or its related organs. All subjects were selected so that other factors that might contribute to increased airway responsiveness were excluded. The methacholine concentration that caused a 20% fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each methacholine concentration, were used to assess airway responsiveness. The geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8 mg/mL (%SEM, 1.74) for IBS patients (P less than 0.0001). The 22.5% +/- 2.5% decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was significantly greater than that of 12.3% +/- 1.5% observed in healthy subjects (P = 0.003). In contrast, the 15.7% +/- 2.0% decrease in FEV1 observed in patients with organic disease was not different from that seen in normal subjects (P = 0.189). We conclude that IBS is associated with increased airway responsiveness following challenge with methacholine.     

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 reactivity in patients with chronic renal failure undergoing haemodialysis

We hypothesized that patients with chronic renal failure may present nonspecific bronchial hyperreactivity due to subclinical interstitial lung oedema. To assess lung function disturbances and methacholine (MTH) bronchial responsiveness in this condition, we studied 12 patients (9 men and 3 women; 41.8 +/- 13.3 yrs (SD] with chronic renal failure undergoing regular haemodialysis (HD). Before HD, mean results of conventional lung function tests were within the normal range: forced expiratory volume in one second (FEV1), 89 +/- 12.9% predicted; forced mid-expiratory flow (FEF25-75), 81 +/- 36.7% predicted; total lung capacity (TLC), 94 +/- 14.6% predicted, but 3 subjects presented mild reduction in lung volumes and 5 individuals showed mild obstructive ventilatory impairment. After HD, maximal expiratory flow rates increased significantly (FEV1, + 8.2 +/- 5.1% (p less than 0.005); FEF25-75, +26.2 +/- 25.9% (p less than 0.005]. Interestingly, these increases in FEV1 after HD correlated with body weight loss during HD (r = 0.74, p less than 0.01). In contrast, pre-HD bronchial reactivity was within the normal range (mean % change in FEV1 after MTH, -3.7 +/- 4.5%; range, +1- -14%) without significant changes in methacholine bronchial responsiveness after HD. We speculate that interstitial lung oedema may play a significant role in lung function impairment observed in patients with chronic renal failure. This study shows that nonspecific bronchial hyperreactivity is not present in clinically stable patients with this disorder.     

Noninvasive assessment of respiratory resistance in severe chronic respiratory patients with nasal CPAP.

Noninvasive measurement of respiratory resistance during nasal ventilatory support could be useful to assess the mechanical status of the patient and to optimize the ventilator settings. The aim was to investigate whether the forced oscillation technique (FOT) applied through a nasal mask allows reliable noninvasive estimation of respiratory resistance (Rrs) in patients with severe chronic respiratory disease. FOT Rrs (5 Hz) and lung resistance (R(L)) measured simultaneously from spontaneous breathing signals by an oesophageal balloon were compared in eight patients with chronic obstructive pulmonary disease and in six patients with a restrictive ventilatory defect due to chest wall disease. Measurements were performed in sitting and supine postures during application of nasal continuous positive airway pressure (CPAP): 4, 8 and 12 cmH2O in obstructive patients and 4 cmH2O in restrictive patients. In the restrictive patients Rrs and R(L) (in cmH2O x s x L(-1)) were virtually coincident: mean+/-SD, 12.6+/-6.1 and 11.6+/-6.6 (r=0.96) in sitting and 9.7+/-3.1 and 10.2+/-3.3 (r=0.92) in supine posture, respectively. In the obstructive patients (CPAP = 4 cmH2O), Rrs slightly underestimated R(L): mean+/-SD, 11.5+/-5.9 and 14.4+/-16.8 (r=0.92) in sitting and 15.0+/-9.8 and 21.1+/-12.6 (r=0.96) in supine posture, respectively. Similar results were found at CPAP = 8 and 12 cmH2O. The results obtained in patients with resistance values in the range typically found in nasal ventilatory support suggest that forced oscillation technique could be valuable to noninvasively estimate a patient's respiratory mechanical resistance.