Diagnostic value of negative expiratory pressure for airway hyperreactivity

STUDY OBJECTIVES: To examine the value of negative expiratory pressure (NEP) in the assessment of methacholine bronchoprovocation testing (BPT). DESIGN: Prospective, observational study. SETTING: Pulmonary function laboratory in a university hospital. PARTICIPANTS: Fifty-nine patients with chronic cough referred from outpatient clinics for methacholine BPT. METHODS: Each subject inhaled successive doubling concentrations of methacholine (from 0.049 to 25 mg/mL) until the FEV(1) decreased for > 20% or the maximum concentration of methacholine was inhaled. NEP was measured in the sitting position during tidal breathing before and after methacholine BPT. The FEV(1) and forced oscillation airway resistance (Rrs) and interrupter airway resistance (Rint) were also obtained simultaneously. A positive BPT result was defined as a fall in FEV(1) > or = 20%. RESULT: At baseline, only five patients had expiratory flow limitation as demonstrated by NEP (EFL-N). There were 39 patients with positive BPT results, and the other 20 patients had negative results. Among the BPT-positive patients, only 13 patients (33.3%) had EFL-N after methacholine challenge. The sensitivity indexes (absolute change/SD) of FEV(1), NEP, Rrs, and Rint were 16.0 +/- 9.6%, 1.1 +/- 1.6%, 3.8 +/- 4.5%, and 5.89 +/- 4.4% (mean +/- SD), respectively. The percentage changes in FEV(1) in BPT-positive patients correlated with the percentage changes in Rrs (r = 0.419, p = 0.008) and only marginally with the percentage changes in Rint (r = 0.307, p = 0.058), but not with the changes in EFL-N (r = 0.048, p = 0.77). CONCLUSION: These data suggest that NEP at sitting position is not sensitive in the assessment of methacholine bronchoprovocation as compared to FEV(1) and airway resistance measurements.     

The opening interrupter technique for respiratory resistance measurements in children

Background and objective: The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back‐extrapolation method (Rint2), with the ‘gold standard’ airway resistance measured by plethysmography (Raw). Methods: The study included 32 asthmatic children and 11 children with cystic fibrosis, aged 5 to 18 years, who were categorized into non‐obstructed (NObs) (n = 27) and obstructed (Obs) (n = 16) groups. Spirometry and the three different resistance measurements were performed on all children. Rint1 and Raw were assessed after a bronchodilator (BD) test in 16 and nine children, respectively, in the Obs group. Results: Raw (0.48 ± 0.20 kPa.s/L) was lower than Rint1 (1.04 ± 0.34 kPa.s/L) and Rint2 (0.63 ± 0.18 kPa.s/L) (P < 0.001). Raw, but neither Rint1 nor Rint2, was significantly higher in the Obs group than in the NObs group (0.57 ± 0.23 vs 0.42 ± 0.16 kPa.s/L, P < 0.05). The differences Rint1‐Raw and Rint2‐Raw were correlated with FEV₁/VC (P < 0.01 and P < 0.001), and Rint1‐Raw was correlated with height (P < 0.001). After BD significant changes in Rint1 and Raw were observed in 5/9 and 7/9 children, respectively. Conclusions: Rint2, as well as Rint1, may be underestimated in the most Obs children and may therefore fail to detect severe obstruction. Rint1 is likely to include a non‐negligible contribution from the tissue component, especially in the youngest children. Although not different between Obs and NObs children at baseline, Rint1 did detect bronchodilation in some Obs children.     

Measurement of airway resistance using the interrupter technique in preschool children in the ambulatory setting.

This study describes the feasibility, repeatability, and interrater reliability of the measurement of airway resistance by the interrupter technique (Rint) in children 2-5 yrs of age, and examines whether reversibility to bronchodilator can be demonstrated in wheezy children. The mean of six Rint values was taken as a measurement. If subjects could complete one measurement and then a second 15 min after bronchodilator, baseline testing and reversibility testing were considered feasible. To measure repeatability, two measurements 30 s apart and measurements before and 15 min after placebo bronchodilator were compared. Measurements by two testers were compared for interrater reliability. Change in Rint in wheezy children was measured after bronchodilator. Fifty-six per cent of 2-3-yr-olds (n=79), 81% of 3-4-yr-olds (n=104) and 95% of 4-5-yr-olds (n=88) completed baseline testing, and 53%, 71% and 91% completed reversibility testing. Baseline measurements were 0.47-2.56 kPa x L(-1) x s. Repeatabilities (2 SD of the mean differences between measurements) at 30 s in the three age bands were 0.21, 0.17 and 0.15 kPa x L(-1) x s and 0.19 kPa x L(-1) x s after placebo. Using 0.21 kPa x L(-1) x s as the threshold for reversibility, reversibility was demonstrated in most wheezy children. Interrater reliability was 0.15 kPa x L(-1) x s. Preschool children can undertake measurements of airway resistance by the interrupter technique in ambulatory settings and reversibility to bronchodilator in wheezy children can be demonstrated. This technique promises to be a useful clinical and research tool.     

Comparison of dynamic lung function indices during forced and quiet breathing in upper airway obstruction, asthma, and emphysema

We compared the dynamic lung function indices in patients with asthma (n = 27), emphysema (n = 20), and UAO (n = 18), with the purpose being to examine whether different patterns of abnormalities could be found and which tests were most discriminative among the three groups. Forced expiratory indices were measured (FEV1; PEF; MEF50%), as well as indices obtained during quiet breathing (Raw; Gaw; Gaw/VL). The three groups were comparable as far as PEF was concerned (about 60 +/- 20 percent of predicted, yet the group with UAO showed significantly larger FEV1 (84 percent of predicted vs 55 percent and 57 percent of predicted in asthma and emphysema respectively), and larger MEF50% (71 percent of predicted vs 25 percent and 23 percent of predicted in the other groups), and the group with asthma had the largest Raw (0.37 +/- 0.18 kPa.s.L-1 vs 0.24 +/- 0.13 in UAO and 0.22 +/- 0.10 in emphysema). From these functional tests, several ratios were derived which were discriminative among the three groups. Upper airway obstruction could be recognized by a significantly lower PEF/MEF50% ratio and higher FEV1/PEF ratio than in the other conditions. Furthermore, a distinction between asthma and emphysema could be made by comparing airway patency during forced and quiet breathing, ie, the MEF50%/Gaw ratio. This ratio was, in fact, significantly different for all three groups, having the lowest value in emphysema (0.19 +/- 0.08 kPa vs 0.44 +/- 0.23 kPa and 0.63 +/- 0.34 kPa in asthma and UAO, respectively). Within the group with UAO, those with variable intrathoracic obstruction showed the least difference from asthma and emphysema for the measured indices.     

Applicability of interrupter resistance measurements for evaluation of exercise-induced bronchoconstriction in children

The interrupter technique is a noninvasive method for measuring air-flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in uncooperative children. The aim of this study was to evaluate applicability interrupter resistance (Rint) measurements in the assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5-12 years with mild to moderate asthma were tested by exercise challenge, consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) were measured before and 10 min after exercise. EIB was defined as a fall of 10% or more in FEV1 after exercise. The repeatability of Rint was assessed, and its response to exercise challenge was compared with current standardized methods. The mean intermeasurement coefficient of variation was 4.6% (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen (36%) of the 50 children had EIB after exercise challenge test. The area under the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%, producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and negative predictive values were 94.1% and 93.9%, respectively. The kappa value between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good, and the results of exercise challenge tests using Rint measurements have excellent agreement with the current standardized methods to detect EIB. Considering that only minimal comprehension and coordination are needed without forced breathing technique, the Rint measurement can provide a useful alternative for assessment of EIB in children unable to perform reliable spirometry.     

Bronchial responsiveness, oscillations of peak flow rate and symptoms in patients with mitral stenosis.

To better characterize airway hyperresponsiveness reported in cardiac patients questionnaire-recorded symptoms, bronchial responsiveness to methacholine (Mch) and to ultrasonically nebulized distilled water (UNDW), diurnal oscillations of peak expiratory flow (PEF) rate were evaluated in 32 patients with moderate mitral stenosis. Twenty patients were responsive to Mch (defined as provocative dose producing a 20% fall in forced expiratory volume in one second (PD20 FEV1) less than 3.2 mg) (geometric mean PD20 FEV1 851 +/- 154 micrograms SE). Only two patients showed a fall in FEV1 greater than 20% after UNDW challenge. Patients responsive to Mch challenge had lower FEV1 as percentage of vital capacity (FEV1/VC) (80 +/- 4.8 vs 83 +/- 3.8%, p less than 0.05), higher coefficient of variation of PEF (CV-PEF) (7.1 +/- 2.8 vs 5 +/- 2.4, p less than 0.05) and higher prevalence of wheeze (70 vs 25%, p less than 0.05) in comparison with patients non-responsive to Mch challenge. CV-PEF was significantly related to FEV1 (r = 0.347, p less than 0.05) and maximal expiratory flow at 50% expired volume (MEF50) (r = 0.405, p less than 0.05). The probability of responding to Mch bronchial challenge increased proportionally with the increase in CV-PEF and the decrease in FEV1, FEV1/VC and MEF50. Airway hyperresponsiveness of patients with mitral stenosis seems to be more similar to that reported in bronchitic than in asthmatic patients.     

Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography.

The impulse oscillation system (IOS) has been developed recently to measure respiratory system resistance (Rrs) and reactance (Xrs) at different frequencies up to > or = 25 Hz. IOS has, however, not been validated against established techniques. This study compared IOS with the classical pseudorandom noise forced oscillation technique (FOT) and body plethysmographic airway resistance (Raw) in 49 subjects with a variety of lung disorders and a wide range of Raw (0.10-1.28 kPa x L(-1) x s). Rrs,IOS was slightly greater than Rrs,FOT, especially at lower frequencies, with a mean +/- SD difference at 5-6 Hz of 0.14 +/- 0.09 kPa x L(-1) x s. Comparisons with the wave-tube technique applied on two analogues indicated an overestimation by IOS. Xrs,IOS and Xrs,FOT were very similar, with a slightly higher resonant frequency with IOS than with FOT (mean difference +/- SD 1.35 +/- 3.40 Hz). Raw was only moderately correlated with Rrn,FOT and Rrs-IOS; although the mean differences were small (0.04 +/- 0.14 kPa x L(-1)s for Rrs6,FOT and -0.10 +/- 0.14 kPa x L(-1) x s for Rrs5,IOS), IOS and FOT markedly underestimated high resistance values. In conclusion, the impulse oscillation system yields respiratory system resistance and reactance values similar, but not identical to those provided by the forced oscillation technique.     

Measurements of resistance by the interrupter technique and of transcutaneous partial pressure of oxygen in young children during methacholine challenge

Measurement of bronchial airway responsiveness requires noninvasive techniques in young children. The study was designed to examine the changes in resistance as measured using the interrupter technique (Rint) at the dose of methacholine (M) that induced a fall in transcutaneous partial pressure in O2 (P(tc)O2) > or = 20% (PD(20)P(tc)O2) in young children. Rint was calculated using the linear back-extrapolation method (Rint(L)) and the end-interrupter method (Rint(EI)). Twenty-two children (mean age, 5.2 +/- 1.1 years; range, 3.4 - 7.1 years) with nonspecific respiratory symptoms (mainly chronic cough, n = 17) were tested. P(tc)O2, Rint(L), and Rint(EI) were measured before the test, after saline challenge (baseline (B)), after each dose of M delivered by a dosimeter, and after bronchodilator (BD) inhalation. P(tc)O2 decreased significantly during M challenge, from 85 +/- 6 mmHg (B) to 62 +/- 9 mmHg (P < 0.05), and increased after BD inhalation, to 82 +/- 8 mmHg. Rint(L) and Rint(EI) increased significantly during M challenge, from 0.94 +/- 0.2 KPa/L/s and 1.11 +/- 0.19 KPa/L/s (B) to 1.27 +/- 0.35 KPa/L/s and 1.47 +/- 0.37 KPa/L/s, respectively (P < 0.05), and decreased after BD inhalation to 0.80 +/- 0.17 KPa/L/s and 0.95 +/- 0.18 KPa/L/s, respectively. Nineteen of 22 children reached the PD(20)P(tc)O2 at a dose of M ranging from 50-400 microg. At the PD(20)P(tc)O2, significant changes in Rint(L) and Rint(EI) (sensitivity index (SI) > or = 2) were found in 79% and 63% of children, respectively. We conclude that: 1) M challenge using P(tc)O2 is safe in young children; and 2) our findings are not in favor of the use of Rint as the only indicator of bronchial reaction in young children during M challenge.     

Pulmonary gas exchange during histamine-induced bronchoconstriction in asthmatic subjects

Bronchial provocation for testing airway hyperreactivity is now well-established. However, the effects of histamine-induced bronchoconstriction on pulmonary gas exchange in man have not been systematically studied. We empirically noted marked decreases in PaO2 in some asthmatic subjects following induced bronchoconstriction. Nine subjects with mild, stable asthma were studied, each on two separate days. The first determined the dose of inhaled histamine necessary to decrease FEV1 by 20 percent and the relationship to lung volume and to pulmonary resistance by the interrupter technique (Rint). On the second day arterial blood gases, ventilation, Rint, and the anatomic (VDan) and physiologic (VDphys) dead spaces were measured simultaneously. There was a significant (p less than 0.05), profound fall in PaO2 (mean, -21.8 mm Hg) and in P(A-a)O2 (mean +14.7 mm Hg) within 5 min after bronchoconstriction, associated with a significant (p less than 0.05) increase in respiratory frequency (mean +5.1 min-1); and decrease in tidal volume (mean, -0.3 L). The ratio VDphys/VT increased significantly (p less than 0.05; mean change, +0.08) even though VDan and VDphys did not. Bronchoconstriction induced the broadening of ventilation (V)/perfusion (Q) ratios, with, most likely, an increase in areas of high V/Q. Histamine-induced bronchoconstriction in mild asthma results in a marked fall in PaO2 due to induced V/Q inequality. Therefore, histamine airway challenge should be used with caution in patients with any preexisting hypoxemia.     

How should airways resistance be measured in young children: mask or mouthpiece?

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (MicroRint) obtained using a mouthpiece were compared with those using a face mask. Fifty children aged 4-7 yrs performed four sets of six Rint measurements; two using a mouthpiece and two using a face mask with integral mouthpiece. Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. Mean Rint values obtained using the mouthpiece were significantly lower than those using the face mask ((mean+/-SD) mouthpiece=0.81+/-0.18 kPa x L(-1) x s, mask=0.88+/-0.24 kPa x L(-1) x s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa x L(-1) x s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p = 0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice. Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.     

Pre/postbronchodilator interrupter resistance values in healthy young children

The interrupter technique estimates flow resistance. It entails occlusion of the airways during tidal breathing while flow and mouth pressure are recorded. This noninvasive technique is easy to use in young children. The aim of the present study was to measure inspiratory and expiratory interrupter resistance (Rint(insp), Rint(exp)) before and after bronchodilator administration in young healthy white children. We designed a multicenter study using a standardized procedure for Rint measurements. Centers in five French cities studied 91 children (48 boys and 43 girls; height, 92 to 129 cm; mean age 5.3 +/- 1.4 years). Mean values were not significantly different for Rint(insp) and Rint(exp) (0.78 +/- 0.21 versus 0.78 +/- 0.20 KPa x L(-1) x second). However, the difference between Rint(insp) and Rint(exp) decreased significantly with age and being positive before 5 years and negative later on (p < 0.02). Rint(insp) and Rint(exp) decreased significantly with height (Rint(insp) [KPa x L(-1) x second] = 2.289 - 1.37. 10(-2) x H [cm], Rint(exp) [KPa. L(-1) x second] = 2.021 - 1.12.10(-2) x H [cm]; p < 0.001). Bronchodilator (salbutamol) administration significantly decreased Rint(insp) and Rint(exp) (p < 0.001). Bronchodilator-induced changes (% of predicted values) in mean Rint(insp) and mean Rint(exp) were -15% (95% confidence interval, -46 to +15%) and -12% (95% confidence interval, -46 to +22%), respectively. Sex did not affect pre- or postbronchodilator values. Data from the present study may prove useful for testing lung function in young children with respiratory disorders who failed to cooperate with forced expiratory maneuvers.     

Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis

The purpose of the present study was to compare measurements of respiratory system resistance by the interrupter method (Rrsint) with those of airway resistance by plethysmography (Raw) in nonobstructed children with asthma or cystic fibrosis (ratio of forced expiratory volume in 1 sec to vital capacity, FEV(1)/VC >/=80% with a forced expiratory flow rate between 25-75% of forced vital capacity, FEF(25-75) >/=75% of normal values) and in obstructed children with the same diseases (FEV(1)/VC <80% and/or FEF(25-75) <75% of normal values). Eighty-one children (47 asthmatics and 34 suffering from cystic fibrosis) aged 5-18 years (mean 11.2 +/- SD 3.4 years) were included in the study. For the overall group, we observed generally lower values for Raw (4.7 +/- 2. 8 cmH(2)O.L(-).s) than for Rrsint20 (extrapolation of the mouth pressure during occlusion to 40 ms after interruption) (5.6 +/- 1.7 cmH(2)O.L(-1).s) (P < 0.02), or for Rrsint40 (extrapolation of the mouth pressure during occlusion to 60 ms after interruption) (6.6 +/- 2.2 cmH(2)O.L(-1).s) (P < 0.001), but there was no difference between Rrsint20 and Raw in the obstructed subgroup. Moreover, we observed a correlation between the difference (Rrsint20 - Raw) expressed in percentage of predicted values and the degree of obstruction estimated by FEV(1)/VC (r = 0.56, P < 0.001). The differences between the specific resistances (sRrsint20 - sRaw, sRrsint40 - sRaw) were also correlated with the severity of the obstruction (r = 0.65, P < 0.001 and r = 0.57, P < 0.001, respectively). We observed also that the tendency to underestimate resistance by Rrsint in obstructed children was not the same in children with asthma and cystic fibrosis. We conclude that the tendency of Rrsint, as measured with our method, to underestimate airway obstruction appears to increase in proportion to the severity of the airway obstruction.     

Prone position improves expiratory airway mechanics in severe chronic bronchitis.

Based on lung parenchyma-airways' interdependence, the present authors hypothesised that prone positioning may reduce airway resistance in severe chronic bronchitis. A total of 10 anaesthetised/mechanically ventilated patients were enrolled. Partitioned respiratory system (RS) mechanics during iso-flow experiments (flow = 0.91 L x s(-1), tidal volume (VT) varied within 0.2-1.2 L), haemodynamics, gas-exchange, expiratory airway resistance (Raw,exp), functional residual capacity (FRC), change in FRC (DeltaFRC), end-expiratory lung volume (EELV), expiratory airway resistance at EELV (Raw,exp,EELV), intrinsic positive end-expiratory pressure (PEEPi), and mean end-expiratory flow were determined in baseline semirecumbent (SRBAS), prone, and post-prone semirecumbent (SRPP) postures. Pronation versus SRBAS resulted in significantly reduced Raw,exp (at VT > or =0.8 L), Raw,exp,EELV (18.3+/-1.4 versus 31.6+/-2.6 cm H2O x L(-1) x s(-1)), inspiratory airway resistance (at VT > or =1.0 L), static lung elastance (at VT < or =0.6 L), "additional" RS/lung resistance (at a range of VTs), DeltaFRC (0.35+/-0.03 versus 0.47+/-0.03 L), EELV (4.92+/-0.49 versus 5.65+/-0.65 L), RS/lung PEEPi (6.7+/-1.1/5.4+/-0.6 versus 8.9+/-1.7/7.8+/-1.1 cm H2O), mean end-expiratory flow (63.9+/-4.2 versus 47.9+/-4.0 mL x s(-1)), and shunt fraction (0.16+/-0.03 versus 0.21+/-0.03); benefits were reversed in SRPP. In severe chronic bronchitis, prone positioning reduces airway resistance and dynamic hyperinflation.     

Response to inhaled bronchodilators and nonspecific airway hyperreactivity in children with cystic fibrosis.

We tested the hypothesis that children with CF who have a significant response to bronchodilator (BD) would respond positively to standard methacholine (Mch) challenge. Our objective was to correlate the response to BD with the concentration that produced a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). We studied 22 patients (12 males), aged 10.5 +/- 0.7 years (mean +/- SE), with a Shwachman-Kulczycki score 82 +/- 2.6 and baseline FEV1 of 80 +/- 4.5% predicted. Baseline expiratory flows, static lung volumes, and airway resistance were measured before and 30 min after inhaled salbutamol. On a separate day, within 2 weeks, a Mch challenge was given, with doubling concentrations from 0.03 to 8.0 mg/mL. A positive challenge was defined as a PC20 less than or equal to 2.0 mg/mL, and a positive response to BD as a greater than 6% of FEV1 increase. Mch challenge yielded 17 responders (R) with a PC20 of 0.5 +/- 0.1 mg/mL, and 5 nonresponders (NR) with a PC20 of 8.8 +/- 2.9 mg/mL. Baseline FEV1 was 77 +/- 5.3% predicted in R compared to 89 +/- 6.3% in NR (P = less than 0.001). History of springtime rhinitis was positive in 9/17 R and 2/5 NR. No significant correlation was found between baseline FEV1 and PC20, or between change in FEV1 post-BD and PC20. A greater than 6% increase in FEV1 was seen in 14/17 R (83% sensitivity) and in none of the 5 NR (100% specificity). In R, 8/17 patients had baseline FEV1 less than 80% predicted, compared to 1/5 in NR.(ABSTRACT TRUNCATED AT 250 WORDS)     

CD86对抗原引起气道嗜酸细胞浸润和气道高反应性作用？…

目的 探讨ＣＤ８６分子对抗原引起气道炎症和气道高反应性的影响,加深认识ＣＤ８６在支气管哮喘发病机制中的作用。方法 应用鸡卵清蛋白致敏和刺激ＢＡＬＢ／ｃ小鼠以诱导嗜酸细胞（ＥＯＳ）聚集到气道,收集支气管肺泡灌洗液（ＢＡＬＦ０细胞并以流式细胞仪检测ＣＤ８６分子的表达水平;观察静脉注射抗ＣＤ８６单克隆抗体后ＢＡＬＦ中ＥＯＳ数和气道反应性的变化。     

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.     

Evaluation of an abbreviated adenosine monophosphate bronchial challenge

RATIONALE: Airway hyperresponsiveness to adenosine monophosphate (AMP) has been validated as a surrogate marker for airway inflammation. We wished to know whether an abbreviated challenge at the final threshold dose would produce the same fall in FEV1 as a full, conventional dose-response challenge. METHODS: Seventeen patients with mild-to-moderate asthma (mean FEV1, 75.5% predicted) attended for a full dose-response protocol, where the highest concentration of AMP to produce > 20% fall in FEV1 was noted, along with the maximum percentage fall and recovery time. Patients returned within 2 days for a further challenge, when they received only the highest concentration (as a single bolus) reached on the previous visit. RESULTS: The mean (+/- SEM) percentage fall in FEV1 after the full challenge was 25.5 +/- 1.3%, and after the abbreviated challenge was 9.4 +/- 2.4%. The mean recovery after the full challenge was 28.13 +/- 4.65 min, and after the abbreviated test was 10.81 +/- 4.27 min. CONCLUSION: An abbreviated challenge using a single bolus dose of AMP grossly underestimates bronchial hyperresponsiveness. Although the pharmacologic half-life of AMP is short (90 s), the lesser response and shortened recovery with the abbreviated challenge suggest a more prolonged physiologic half-life, which in turn may have implications for abbreviated challenge protocols.     

Interrupter resistance in preschool children: measurement characteristics and reference values

There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique (interrupter resistance [Rint]) and obtained reference values in children from a general population, 2 to 7 yr of age. Accuracy was studied by comparisons of Rint with plethysmographic airway resistance (Raw) in 20 patients (7 to 14 yr) with mild to severe chronic airways obstruction and was satisfactory in patients with FEV(1) > 60% predicted. The technique proved sensitive enough to detect changes in airway caliber within a small group of 12 children who developed mild respiratory tract infections. Among children from a general population, subgroups with mild respiratory symptoms or mild respiratory disease had higher mean Rint values. Airway obstruction was better detected using expiratory rather than inspiratory interruptions, both programmed at peak tidal ventilatory flow. Reproducibility within subjects was satisfactory (intraclass correlation 0.82 and 0.79). The same applied to interobserver agreement (intraclass correlation 0.98). The interrupter technique proves to be a reliable and practical test of airway function, suitable for clinical and epidemiologic studies in preschool children.     

Pulmonary function and bronchial reactivity in asthmatics during low-level formaldehyde exposure

This study evaluated whether formaldehyde, at concentrations similar to those found in the indoor environment, could produce adverse effects on the lower airway of 15 asthmatic persons with documented bronchial hyperresponsiveness who were exposed for 90 min in a climate chamber to clean air containing formaldehyde vapor at levels of 0.85 mg/m3, 0.12 mg/m3, and 0.008 mg/m3. No significant changes in forced expiratory volume in 1 sec (FEV1), airway resistance (Raw), specific airway resistance (SRaw), and flow-volume curves could be detected during formaldehyde exposure. Furthermore, histamine challenge tests performed immediately after formaldehyde exposure showed no evidence of changes in bronchial reactivity. No late reactions were registered during the first 14-16 hr after exposure. The results suggest that residential levels of formaldehyde are of minor importance in the emergence of pulmonary symptoms. Discrepancies between the present study and previous data may be due to differences in environmental conditions.     

The effect of ipratropium nasal spray on bronchial methacholine challenge

PURPOSES: To determine the effect ipratropium bromide nasal spray has on methacholine challenge testing for airway hyperresponsiveness. MATERIALS AND METHODS: Ten subjects with known airway hyperresponsiveness to methacholine who had been clinically stable in the preceding 2 months participated in a randomized, double-blind, placebo-controlled, crossover study. Methacholine challenge testing was conducted on successive days: day 1 after pretreatment with aqueous 0.03% nasal ipratropium, and day 2 with normal saline solution placebo. RESULTS: The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was higher after nasal ipratropium than after saline solution placebo (2.1 mg/mL vs 1.6 mg/mL, p = 0.02). This difference is equal to approximately one-half concentration difference, probably within the limits of reproducibility of the test. CONCLUSIONS: Pretreatment with nasal ipratropium results in a small increase in PC20. Although this difference achieves statistical significance, it is probably not clinically significant.