Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis.

Many children with cystic fibrosis (CF), receiving modern, aggressive CF care, have normal spirometry results. This study aimed to see if homogeneity of ventilation distribution is impaired early in the course of CF lung disease, and if ventilation inhomogeneity is a more frequent finding than abnormal spirometry in children benefiting from modern CF care. The study compared spirometry findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung clearance index (LCI)) from multiple-breath inert gas washout in 43 children with CF, aged 3-18 yrs, and 28 healthy children. In total, 10/43 CF subjects (23%) had reduced forced expiratory volume in one second (FEV1) and 14/34 (41%) showed abnormal maximum expiratory flow at 25% of forced vital capacity (MEF25). In contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal in 22/33 CF subjects with normal FEV1, versus 0/28 controls (p<0.001), and abnormal MR was found in 10/20 CF subjects with normal MEF25, versus 0/22 controls (p<0.001). Nine of the 10 CF subjects with reduced FEV1 and 12/14 with abnormal MEF25 showed abnormal MR. Inert gas washout discloses airway dysfunction in the majority of children with cystic fibrosis with normal lung function judged by spirometry. These findings suggest that multiple-breath inert gas washout is of greater value than spirometry in detecting early cystic fibrosis lung disease.     

Whole-lung lavage: a successful treatment for restoring acinar ventilation distribution in primary acquired pulmonary alveolar proteinosis

A 51-year-old active smoker with primary acquired pulmonary alveolar proteinosis (PAP) diagnosed by biopsy and anti-GM-CSF antibodies was treated safely with whole-lung lavage (WLL). This resulted in a rapid improvement of symptoms and arterial blood oxygenation, but not of standard lung function parameters. However, we also performed the multiple-breath nitrogen washout (MBW) test to determine the lung clearance index (LCI) as well as indices of acinar ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)). At baseline, a distinct abnormality was seen for S(acin) and LCI, while S(cond) was at the upper limit of normal for this subject. S(acin), in particular, was in excess of the S(acin) abnormality corresponding to a 20-pack-year smoking history. Immediately after WLL, S(acin) and S(cond) both fell to within a normal range while LCI also decreased but remained abnormal. The S(acin) decrease was much greater than the S(cond) decrease, which was to be expected after 1 week of smoking cessation at the hospital (smoking was resumed after release from hospital). A follow-up visit 7 weeks after WLL revealed a spectacular improvement on CT scan and improvements in standard lung function. Another follow-up visit 14 weeks after WLL showed further improvements in standard lung function, and both S(acin) and S(cond) remained well within the normal range, and LCI was above the upper limit of normal. We conclude that in this patient, removal of excess surfactant by WLL resulted in a restored ventilation distribution in most of the distal air spaces.     

Evidence of improved small airways function after azithromycin treatment in diffuse panbronchiolitis

A 67-year-old never-smoker was diagnosed with diffuse panbronchiolitis (DPB) and was started on 250 mg azithromycin twice weekly. Over a 16-month observation period, lung function was assessed monthly, including a dedicated small airways test, the multiple breath nitrogen washout (MBW) with indices S(cond) and S(acin) of ventilation heterogeneity at the level of the conductive and acinar air spaces, respectively. Baseline measurements indicated moderate airway obstruction, air trapping and considerable dysfunction of the small airways around the acinar entrance. Treatment resulted in excellent symptomatic improvement paralleled by marked improvements in FEV(1), FVC, RV/TLC, S(cond) and S(acin); by contrast, there were no consistent changes in FEF(75) or TL(CO). While improvements were such that S(cond) fell within normal limits after 5 months, S(acin) remained abnormal even after 16 months of treatment. This suggests a distinct acinar structural abnormality in DPB that cannot be reversed by azithromycin.     

Noninvasive assessment of airway alterations in smokers: the small airways revisited

It has been shown that structural changes in small airways of smokers with average smoking histories greater than 35 pack-years could be reflected in the single-breath washout test. The more sophisticated multiple breath washout test (MBW) has the potential to anatomically locate the affected small airways in acinar and conductive lung zones through increased phase III slope indices S(acin) and S(cond), respectively. Pulmonary function, S(acin), and S(cond) were obtained in 63 normal never-smokers and in 169 smokers classified according to smoking history (< 10 pack-years; 10-20 pack-years; 20-30 pack-years; > 30 pack-years). Compared with never-smokers, significant changes in S(acin) (p = 0.02), S(cond) (p < 0.001), and diffusing capacity (DL(CO); p < 0.001) were detected from greater than 10 pack-years onwards. Spirometric abnormality was significant only from greater than 20 pack-years onwards. In smokers with greater than 30 pack-years and DL(CO) less than 60% predicted, the presence of emphysema resulted in disproportionally larger S(acin) than S(cond) increases. We conclude that S(cond) and S(acin) can noninvasively detect airway changes from as early as 10 pack-years onwards, locating the earliest manifestations of smoking-induced small airways alterations around the acinar entrance. In these early stages, the associated DL(CO) decrease may be a reflection of ventilation heterogeneity rather than true parenchymal destruction. In more advanced stages of smoking-induced lung disease, differential patterns of S(acin) and S(cond) are characteristic of the presence of parenchymal destruction in addition to peripheral airways alterations.     

Ventilation inhomogeneities in relation to standard lung function in patients with cystic fibrosis

Based on serial lung function measurements performed in 142 children (68 males; 74 females) with cystic fibrosis (CF), prospectively evaluated over an age range of 6 to 20 years, we attempted to determine whether the lung clearance index (LCI) as a measure of ventilation inhomogeneities could be a discriminating factor of disease progression. Annual follow-up lung function measurements featuring FRC determined by whole-body plethysmography and multibreath nitrogen washouts, effective specific airway resistance, flow-volume curves, LCI, and gas exchange characteristics were analyzed by linear mixed-model analysis and Kaplan-Meier statistics. The earliest occurring and strongest factor of progression was the LCI, followed by maximal expiratory flow (MEF(50)) and FRC determined by plethysmography (p < 0.0001). Associations between onset of chronic Pseudomonas aeruginosa infection and CF transmembrane conductance regulator (CFTR) genotype with FEV(1) (p = 0.027) and FVC (p = 0.007) were identified. The study shows that the LCI predicts earlier in life and represented much better functional progression than FEV(1). Moreover, there is no single functional predictor of progression in CF, but aside from risk factors, such as onset of chronic P. aeruginosa infection and genotype, pulmonary hyperinflation, airway obstruction, and ventilation inhomogeneities are important pathophysiologic processes that should be evaluated concomitantly as determinants of lung progression in CF.     

Ventilation homogeneity improves with growth early in life

Some studies have suggested that lung clearance index (LCI) is age-independent among healthy subjects early in life, which implies that ventilation distribution does not vary with growth. However, other studies of older children and adolescents suggest that ventilation becomes more homogenous with somatic growth. We describe a new technique to obtain multiple breath washout (MBWO) in sedated infants and toddlers using slow augmented inflation breaths that yields an assessment of LCI and the slope of phase III, which is another index of ventilation inhomogeneity. We evaluated whether ventilation becomes more homogenous with increasing age early in life, and whether infants with chronic lung disease of infancy (CLDI) have increased ventilation inhomogeneity relative to full-term controls (FT). FT (N = 28) and CLDI (N = 22) subjects between 3 and 28 months corrected-age were evaluated. LCI decreased with increasing age; however, there was no significant difference between the two groups (9.3 vs. 9.5; P = 0.56). Phase III slopes adjusted for expired volume (S(ND)) increased with increasing breath number during the washout and decreased with increasing age. There was no significant difference in S(ND) between full-term and CLDI subjects (211 vs. 218; P = 0.77). Our findings indicate that ventilation becomes more homogenous with lung growth and maturation early in life; however, there is no evidence that ventilation inhomogeneity is a significant component of the pulmonary pathophysiology of CLDI.     

Effect of albuterol on maximal exercise capacity in cystic fibrosis

BACKGROUND: Inhaled, short-acting beta-adrenergic agonists (SAbetaAs) are widely prescribed in cystic fibrosis (CF) subjects, despite a lack of convincing data for efficacy and the potential for these agents to result in airway instability. We tested the hypothesis that inhaled albuterol would improve maximal exercise performance in CF subjects with airflow obstruction, as a result of acute bronchodilation. METHODS: Randomized, double-blind, placebo-controlled crossover study of the effect of inhaled albuterol on maximal exercise performance in 20 stable adult CF patients (mean +/- SD age, 23.3 +/- 6.1 years; FEV(1), 57.65 +/- 17.13% of predicted). RESULTS: Ventilatory limitation to exercise was demonstrated in 16 subjects (80%). Significant bronchodilation occurred with exercise alone (end-exercise FEV(1), 2.24 +/- 0.8 L; vs preexercise FEV(1), 2.09 +/- 0.77 L; p < 0.0001), but albuterol resulted in significantly greater exercise-induced bronchodilation than placebo (change in FEV(1), 0.3 +/- 0.15 L vs 0.15 +/- 0.11 L; 95% confidence interval [CI], + 0.07 to + 0.23; p < 0.001). However, there was no difference in maximal workload achieved (albuterol, 158 +/- 46 W; vs placebo, 158 +/- 45 W; 95% CI, - 4.41 to + 4.71; p = 0.95), nor any other measure of exercise performance including maximal oxygen uptake. CONCLUSIONS: Despite causing significant acute bronchodilation, inhaled albuterol did not improve maximal exercise performance in ventilatory-limited CF adults, adding to the body of literature that fails to show any clinical benefit of SAbetaAs in CF subjects. The current results provide further evidence to question the widespread use of these agents, although the potential for adrenergic beta-agonists to instead improve submaximal exercise performance merits further investigation.     

Lung volumes measured by the forced rebreathing technique in children with airways obstruction.

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.     

Bronchodilation with a potent and selective leukotriene D4 (LTD4) receptor antagonist (MK-571) in patients with asthma.

The sulfidopeptide leukotrienes LTC4, LTD4, and LTE4 can cause airway smooth muscle contraction and have been implicated in the pathophysiology of asthma. MK-571 is a selective, potent LTD4 receptor antagonist that could attenuate airway obstruction in asthma by inhibiting the actions of sulfidopeptides at the LTD4 receptor site. The objectives of this study were to investigate the potential for MK-571 to cause bronchodilation in asthma patients with existing airway obstruction and to evaluate its effect on the bronchodilation response to an inhaled beta 2-agonist (albuterol). Twelve male patients (ages 19 to 42 yr) with asthma (baseline FEV1 50 to 80% predicted) participated in this placebo-controlled, randomized, two-period, cross-over study. On separate treatment days, each patient received either MK-571 or placebo intravenously for 6 h; inhaled albuterol was administered at the fifth and sixth hour of MK-571/placebo treatment to achieve maximal bronchodilation on that study day. Spirometry (forced expiratory volume in 1 s, FEV1) was monitored at intervals throughout each study period. MK-571 caused clinically significant bronchodilation; the increase in FEV1 above baseline, 20 min after the start of the MK-571 infusion, was 22 +/- 3.9% compared with 1.3 +/- 2.3% for placebo (mean +/- SE, p < 0.01). This degree of bronchodilation was maintained throughout the MK-571 infusion. In addition, bronchodilation from inhaled albuterol appeared additive with MK-571. Finally, baseline airway obstruction correlated with the degree of bronchodilation achieved with MK-571 (r = -0.73; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of procaterol treatment on beta-adrenergic bronchodilation and polymorphonuclear leukocyte responsiveness

Procaterol is a new and effective beta-adrenergic bronchodilator. To determine if procaterol administration could cause tachyphylaxis, airway and leukocyte beta-adrenergic function were monitored in 10 patients with asthma during two 4-wk, double-blind treatment periods, each preceded by a 2-wk beta-agonist washout. Treatment periods were randomized to placebo or procaterol (2 wk, 0.1 mg/day; 2 wk, 0.2 mg/day). At each 7 biweekly evaluations, the patient's cumulative bronchodilator dose-response to inhaled isoproterenol (0.1 to 0.64%) was measured, and venous blood was collected to quantitate, in vitro, the polymorphonuclear leukocyte (PMN) beta-adrenergic receptor's 125Iodo-cyanopindolol (125I-CYP) ligand binding and the PMN cyclic AMP response to isoproterenol and procaterol. Neither the airway nor leukocyte beta-adrenergic characteristics were changed during placebo treatment. Procaterol treatment reduced (p less than 0.05) the maximal 125I-CYP binding to PMN membranes but only during the initial 2 wk at low dosage. The percent PMN cyclic AMP increase to procaterol (10(-5) M) was also significantly (p less than 0.05) less during active treatment (141 +/- 40%) than during washout (256 +/- 24%) or placebo (257 +/- 32%). In contrast, procaterol treatment did not alter the acute isoproterenol bronchodilation response as measured by either the percent improvement in FEV1 or the dose required to produce 50% maximal bronchodilation. The duration of bronchodilation was not measured. Therefore, although procaterol therapy of asthma is associated with decreased PMN beta-adrenergic function, airway smooth muscle function appears not to be altered.     

Ventilation inhomogeneity assessed by nitrogen washout and ventilation-perfusion mismatch by capnography in stable and induced airway obstruction

Few studies have been published on gas distribution in the lung during acute and stable airway obstruction in children. Multiple breath nitrogen (N(2)) washout is an established method for assessing ventilation inhomogeneity, while the tidal breathing capnogram may be used as an indicator of ventilation-perfusion (V(')(A)/Q) mismatch. We hypothesized that significant V(')(A)/Q mismatch is not seen in stable airway obstruction unless obstruction is severe, and that stable and induced airway obstruction of similar severity would result in different degrees of V(')(A)/Q mismatch. To test this hypothesis, we performed spirometry measurements of forced expiratory volume in 1 sec (FEV(1)), multiple breath N(2) washout, and tidal breathing capnography in 11 young patients (9-30 years) with cystic fibrosis, 37 asthmatic patients (8-18 years), and 34 healthy subjects (7-20 years). Lung function was measured at rest, after airway obstruction induced by cold dry air hyperventilation or methacholine challenge, and after beta(2)-agonist treatment. V(')(A)/Q mismatch was assessed from the slopes of the phases II and III of the capnogram. We observed a normal capnogram during stable obstruction of moderate severity despite significant ventilation inhomogeneity. In patients with severe stable obstruction and in those with induced airway obstruction significant ventilation inhomogeneity and pathological capnograms were seen. Induced airway obstruction, resulted in a more pathological capnogram than stable obstruction of similar severity. beta(2)-agonist treatment reduced ventilation inhomogeneity, but did not improve the capnogram. Our findings are compatible with the presence of an efficient pulmonary blood flow regulatory mechanism that adequately compensates for chronic ventilation inhomogeneity of moderate severity, but not for severe or sudden airway obstruction.     

支气管哮喘急性发作缓解前后的小气道功能测定

目的肺功能检测在支气管哮喘治疗前后小气道功能的评价作用研究。方法选择31例急性期支气管哮喘患者和30名健康志愿者作为对照,测定其急性期和缓解期肺功能,并加以比较。结果 31例支气管哮喘患者,在哮喘急性发作期测舒张实验全部阳性,哮喘组患者急性发作期和缓解期FEV1占预计值%及FEV1/FVC比较差异有统计学意义(P<0.01);哮喘组患者缓解期和健康对照组受试对象FEV1占预计值%和FEV1/FVC比较差异无统计学意义(P>0.05)。结论急性期哮喘患者均存在大、小气道功能异常,缓解期哮喘患者大气道功能恢复,小气道功能虽有一定恢复,但与正常健康对照组比较仍存在异常。     

Improvement in bronchodilation following deep inspiration after a course of high-dose oral prednisone in asthma

BACKGROUND: Bronchodilation following deep inspiration is usually impaired in patients with asthma. This might be due to changes in airway mechanics in the presence of inflammation or structural changes within the airways. Although inhaled corticosteroid treatment has been shown to improve airway responses to deep inspiration in patients with asthma, airway inflammation can persist despite inhaled corticosteroid treatment, and thus could still influence the airway mechanics during deep breaths. We hypothesized that oral steroid treatment further optimizes deep inspiration-induced bronchodilation in clinically stable asthmatic patients who are receiving therapy with inhaled corticosteroids. METHODS: Twenty-four atopic patients with mild-to-moderate persistent asthma (FEV1, > 70% predicted; provocative concentration of methacholine causing a 20% fall in FEV1 [PC20], < 8 mg/mL), who were treated with 250 to 2,000 mug of beclomethasone-dipropionate or equivalent, participated in a parallel-design, double-blind study. Before and after treatment with 0.5 mg/kg/d prednisone or placebo for 14 days, a methacholine challenge was performed. Deep inspiration-induced bronchodilation was measured by the ratio of flow at 40% of FVC on the flow-volume curve after maximal inspiration/flow at 40% of FVC on the flow-volume curve after partial (60% of FVC) inspiration (M/P ratio). RESULTS: The M/P ratio significantly increased from a mean of 1.31 (range, 1.0 to 1.7) to 1.49 (range, 1.1 to 2.3) in the prednisone group. Interestingly, the improvement in the M/P ratio did not correlate with an accompanying significant increase in PC20 for methacholine (mean change, 1.02; SD doubling dose, 0.97) and a decrease in exhaled nitric oxide (mean change, 14 parts per billion [ppb]; SD, 33.4 ppb). CONCLUSIONS: Systemic antiinflammatory treatment in addition to maintenance therapy with inhaled corticosteroids increases bronchodilation by deep inspiration in patients with mild-to-moderate persistent asthma. This suggests that residual inflammation impairs airway mechanics in asthma patients.     

Long duration of airway but not systemic effects of inhaled formoterol in asthmatic patients

RATIONALE: Formoterol is approved as asthma rescue medication in many countries. The exact duration of the airway vs. systemic effects of formoterol compared with another rescue medication, salbutamol, has not been evaluated. OBJECTIVE: To assess the duration of airway bronchodilatory effects vs. systemic effects of inhaled formoterol and salbutamol in asthmatic patients. METHODS: Twenty-six patients with stable and reversible asthma were given single doses of formoterol dry-powder inhaler (OxisTurbuhaler) 2x9 microg (lower dose; LD) and 6x9 microg (higher dose; HD), salbutamol (VentolinDiskhaler) 3x400 microg (LD) and 9x400 microg (HD), and placebo in a randomized, double-blind, crossover trial. Airway and systemic effects were assessed by forced expiratory volume in 1s (FEV1), serum potassium, blood pressure, corrected QT-interval (QTc), and palpitation and tremor scores. Time with clinically relevant bronchodilation (FEV1 increase 12%) without clinically relevant markers of systemic effects (serum potassium suppression 0.2 mmol/L, QTc-prolongation 20 ms, or heart rate increase 8 beats per minute) was evaluated. RESULTS: Bronchodilation was maintained for 24h with both formoterol doses and for 7-11h with salbutamol. Maximum bronchodilation and systemic effects were similar after formoterol and salbutamol, except for statistically significantly larger maximum heart rate and palpitation and tremor scores after salbutamol. Systemic responses were similarly brief for formoterol and salbutamol (7 h). CONCLUSIONS: The airway effects of inhaled formoterol are of long duration, whereas the systemic effects are of a similarly short duration as salbutamol. Thus, the time with clinically relevant bronchodilation without systemic effects is substantially longer after formoterol than after salbutamol.     

Informative value of simple multibreath nitrogen washout measurements for clinical and research purposes

Some simple multibreath nitrogen washout indexes quantifying inspired gas distribution and ventilatory efficiency were obtained in a group of patients with mild to advanced chronic obstructive pulmonary disease (COPD) and studied in their relationships with routine pulmonary function tests. The indexes (lung clearance index (LCI), mixing ratio (MR) and data obtained by graphic analysis of the washout curve) were correlated with spirometric, pulmonary mechanics and arterial blood gas measurements, but only 8-38% of the interindividual variation in these indexes was explained by the above routine tests. An additional 5-13% of the variation was explained by the washout tidal volume (VT); this finding may reflect changes in gas distribution with VT and/or the influence of the dead space on ventilatory efficiency. Our data indicate that, in patients with COPD, nitrogen washout indexes tend to change in parallel with routine pulmonary function tests, reflecting the severity of the disease; these indexes also contain specific information (in addition to that provided by routine physiologic tests), presumably related to the distribution and efficiency of ventilation. Nitrogen washout measurements may thus represent a helpful adjunct to routine pulmonary function testing; LCI and MR appear to be particularly convenient for practical purposes because of their simplicity, and an informative content comparable with that of more complex indexes.     

Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity

The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV(1)/FVC <0.70. We examined relationships between indices of airway obstruction and lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV(1) decreased, while VC and IC decreased linearly. Regardless of baseline FEV(1), the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.     

Effects of long-acting bronchodilators and placebo on histamine-induced asthma symptoms and mild bronchusobstruction

STUDY OBJECTIVE: Accurate perception of airway caliber remains an important issue in asthma management. The way bronchodilation is perceived is partly related to the perception of the efficacy of bronchodilators in relieving complaints. In the present study, we compared the effects of salmeterol, formoterol and placebo on relief of histamine-induced asthma symptoms and mild bronchusobstruction. METHODS: In this randomized controlled, double blind study, 30 asthmatics were challenged with histamine until forced expiratory volume in 1s (FEV(1)) fell with > or =20%. Subjects received salmeterol, formoterol or placebo after the histamine provocation. Pulmonary function (FEV(1)) and asthma symptoms (Asthma Symptom Checklist, Borg Dyspnea Scale) were assessed 5 and 20 min later. RESULTS: FEV(1) improved significantly more in the salmeterol and formoterol group than in the placebo group (P<0.001, P<0.001 and P<0.05, respectively). Salmeterol and formoterol were not different with regard to the pulmonary function recovery. No significant differences were found between the effects of salmeterol, formoterol and placebo on any of the symptom responses at the different time points. CONCLUSIONS: We conclude that after a histamine-induced mild bronchusobstruction, a similar asthma symptom recovery occurred when inhaling salmeterol, formoterol or placebo, despite better recovery of pulmonary function in the active drug conditions.     

Overall and peripheral inhomogeneity of ventilation in patients with stable cystic fibrosis

We studied distribution of ventilation in patients with cystic fibrosis (CF) who had not had an exacerbation for some time. Patients performed either the vital capacity nitrogen (N(2)) single-breath washout test (VC test) or a modified single-breath washout consisting of 1 L inspired from functional residual capacity (FRC test) of 90% oxygen (O(2)), 5% helium (He), and 5% sulfur hexafluoride (SF(6)). We computed the slopes of phase III of N(2) concentration from the VC test (S(N2) (VC)) and the phase III slopes of the He (S(He)): The SF(6) (S(SF6)), and curves from the FRC test. S(N2) (VC) may be regarded as an index of overall ventilation and the difference (S(SF6) - S(He)) as an index of peripheral ventilation. Three groups were studied: CF, 28 CF patients (8-36 years of age); normal controls (NC), 33 normal nonsmokers (9-55 years of age); and a smoking group (SG), 42 non-CF smoking patients (39-79 years of age). Compared to the NC group, S(N2) (VC) is increased in the CF group, reflecting an overall ventilation impairment. There is no difference in S(N2) (VC) between the CF group and the SG group, suggesting that S(N2), though sensitive, is nonspecific. Compared to both NC and SG groups, (S(SF6) - S(He)) is decreased in the CF group, being on the average negative. This may imply that there is a peripheral impairment in the distribution of ventilation that originates in terminal and respiratory bronchioles. Negative (S(SF6) - S(He)) is statistically associated with the youngest CF patients, suggesting that terminal and respiratory bronchiolar involvement is linked to early stages of the disease. In older CF patients, (S(SF6) - S(He)) is more often positive, suggesting that even more distal airways, such as alveolar ducts, become involved in peripheral inhomogeneity of ventilation.