The paradoxical response to short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease

BackgroundThere are a few studies about paradoxical bronchodilator response (BDR), which means a decrease in forced expiratory volume in 1 second (FEV₁) or forced vital capacity (FVC) after short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease (COPD). We evaluated the effect of paradoxical BDR on the clinical outcomes of COPD patients in South Korea.MethodsWe analyzed the KOrea COpd Subgroup Study team (KOCOSS) cohort data in South Korea between January 2012 and December 2017. BDR was defined as at least a 12% and 200-mL reduction in FEV₁ or FVC after bronchodilator administration.ResultsA total of 1,991 patients were included in this study. A paradoxical BDR was noted in 57 (2.9%) patients and was independently associated with worse dyspnea and poor quality of life. High C-reactive protein (CRP) levels were associated with a paradoxical BDR (OR, 1.05; 95% CI, 1.01–1.09; P=0.003). However, paradoxical BDR was not associated with severe acute exacerbations. Pre-bronchodilator FEV₁ (L) showed a higher area under the curve (AUC) for predicting severe acute exacerbations than the post-bronchodilator FEV₁ (L) in the paradoxical BDR group (0.788 vs. 0.752).ConclusionA paradoxical reduction of FEV₁ or FVC after bronchodilator administration may be associated with chronic inflammation in the airway and independently associated with worse respiratory symptoms and poor quality of life.     

Oscillometric and spirometric bronchodilator response in preschool children with and without asthma

BACKGROUND:

Bronchodilator responses (BDR) are routinely used in the diagnosis and management of asthma; however, their acceptability and repeatability have not been evaluated using quality control criteria for preschool children.

OBJECTIVES:

To compare conventional spirometry with an impulse oscillometry system (IOS) in healthy and asthmatic preschool children.

METHODS:

Data from 30 asthmatic children and 29 controls (two to six years of age) who underwent IOS and spirometry before and after salbutamol administration were analyzed.

RESULTS:

Stable asthmatic subjects significantly differed versus controls in their spirometry-assessed BDR (forced expiratory volume in 1 s [FEV₁], forced vital capacity and forced expiratory flow at 25% to 75% of forced vital capacity) as well as their IOS-assessed BDR (respiratory resistance at 5 Hz [Rrs₅], respiratory reactance at 5 Hz and area under the reactance curve). However, comparisons based on the area under the ROC curve for ΔFEV₁ % initial versus ΔRrs₅ % initial were 0.82 (95% CI 0.71 to 0.93) and 0.75 (95% CI 0.62 to 0.87), respectively. Moreover, the sensitivity and specificity for ΔFEV₁ ≥9% were 0.53 and 0.93, respectively. Importantly, sensitivity increased to 0.63 when either ΔFEV₁ ≥9% or ΔRrs₅ ≥29% was considered as an additional criterion for the diagnosis of asthma.

CONCLUSION:

The accuracy of asthma diagnosis in preschool children may be increased by combining spirometry with IOS when measuring BDR.     

A Comparison of Two Delivery Methods for Aerosolized Metaproterenol Sulfate

The bronchodilator response to metaproterenol sulfate delivered by metered-dose inhaler (MDI) with a spacer device (Aerochamber®) and by jet nebulizer was studied in 15 asthmatic patients. The mean percent increase in absolute forced expiratory volume in 1 second (FEV₁) with an MDI plus Aerochamber was 28.6%, and 28.8% with jet nebuliza-tion. There were no significant differences in the mean percent increases in FEV₁, forced vital capacity (FVC), maximum midflow rate (MMFR), and peak expiratory flow rate (PEFR) with the two delivery methods. It is concluded that there is no difference in the bronchodilator responses to metaproterenol sulfate delivered by MDI plus Aerochamber or by jet nebulizer. The MDI plus Aerochamber has the advantage of being less expensive and more convenient to use.     

Forced expiratory maneuvers in children aged 3 to 5 years

There is no consensus about reproducibility and reliability of spirometry in young children. We evaluated forced expiratory maneuvers from 98 children aged 3 to 5 years with a variety of respiratory disorders before and after bronchodilator treatment. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV,) were analyzed for reproducibility by the American Thoracic Society criteria and for reliability based on the coefficient of variation (CVYo). Over 90% of the patients cooperated, however, while 95% could exhale for at least 1 second, very few generated an FEV, on all 6 “best” efforts. This clearly improved with age. Of all patients nearly 60% performed reproducible pre-and postbronchodilator sets of FVC but only 32% performed reproducible sets of FEV₁. Based on the CV%, those patients who could reproducibly perform an FVC and FEV, did it quite reliably (mean CV%, 9.38 and 7.01 for FVC and FEV₁, respectively). We conclude that while some very young children can perform spirometry, reliability of performance cannot be assumed in this age group. Pediatr Pulmonol. 1994;18:144–149. © 1994 Wiley-Liss, Inc.     

Bronchodilator Response in Asthmatic Children is Significantly Reduced When Measured Immediately After Methacholine Challenge

Aim: Airway responses to a bronchodilator (BDR) and to methacholine are frequently measured in the assessment of childhood asthma and in pulmonary research. For practical reasons, we wondered whether it would be possible to obtain a reliable BDR immediately after completion of a methacholine challenge test. To this end, we compared BDR with and without a preceding methacholine challenge. Methods: The BDR was measured twice in random order on consecutive days in 24 asthmatic children with methacholine hyperresponsiveness. It was calculated as the change in forced expiratory volume in one second (FEV₁) before and 20 min after inhaling 800 µg of salbutamol (metered dose inhaler with a spacer), expressed as a percentage of the predicted value (ΔFEV₁%pred). On one day BDR was measured immediately after completing a methacholine challenge, on the other day without any preceding challenge. Results: Mean(SD) baseline FEV₁%pred was not significantly different between test days [98.6(14.2)% and 98.1(13.8)%, respectively, p=0.53]. The geometric mean provocative dose of methacholine producing a 20% fall in FEV₁ (PD₂₀) was 56.2 µg (range 10.3–306.2 µg). The mean(SEM) BDR without preceding methacholine challenge was 10.8(1.4)%, while after preceding methacholine challenge it was 5.2(1.5)% (mean difference 5.6%, 95% CI 3.0%–8.1%, p<0.001). Mean(SEM) postbronchodilator FEV₁%pred was 109.4(3.0)% without and 103.4(2.7)% with preceding methacholine challenge (mean difference 6.0%, 95% CI 3.5%–8.6%, p<0.001). Conclusion: A preceding methacholine challenge significantly reduces BDR in asthmatic children. Therefore, a BDR, measured immediately after completing a methacholine challenge, cannot be used as a substitute for a separate bronchodilator test.     

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants

We hypothesized that a new test of infant lung function, less affected by shifts in lung volume, might better detect bronchodilator effects. Using the raised volume forced expiration technique (RVFET), the effect of a bronchodilator on lung function was studied in 22 infants with a history of recurrent wheeze and five healthy infants. Forced expiratory volume in 0.75 s (FEV_0.75), forced expiratory vital capacity (FVC), and forced expiratory flow at 75% of FVC (FEF_75%) were measured by forcing expiration, using an inflatable jacket from a lung volume set by an inspiratory pressure of 20 cm H₂O. A minimum of five measurements were made at baseline and following the administration of 500 μg of salbutamol from a metered dose inhaler via a small volume metal spacer. Changes in lung function in the group of 25 infants who received salbutamol were compared to seven infants who received placebo aerosol. No significant changes occurred in measures of lung function following salbutamol administration when compared to baseline or placebo despite a significant increase in heart rate. A shift in lung volume is unlikely the reason why infants do not demonstrate a change in forced expiration following bronchodilator administration. Pediatr Pulmonol. 1998; 26:35–41. © 1998 Wiley-Liss, Inc.     

Inspiratory flow limitation in children with bronchopulmonary dysplasia

The objective of this study was to compare pulmonary function tests of children with bronchopulmonary dysplasia (BPD) and asthma, and to evaluate children with BPD for evidence of upper airway obstruction. This is a case-control retrospective study of pulmonary function tests (PFTs) of 11 children with BPD between 5 and 8 years of age who were followed by pediatric pulmonologists, and of 32 age- and height-matched children with asthma. The median forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) were significantly lower in the BPD group (0.86 L, 0.79 L, 120 L/min) than in the asthmatic group (1.34 L, 1.21 L, 155 L/min; P = 0.002, P = 0.007, P = 0.004, respectively). Both groups were equally hyperinflated (median thoracic gas volume 155% of predicted values in the BPD compared to 152% predicted in the asthma group; P = 0.67), and both groups showed decreases in air-trapping after a bronchodilator. The ratios of forced expiratory flow at 50% of the FVC to forced inspiratory flow at 50% of the FVC (FEF_50%/FIF_50%) and FEV₁ to PEF (FEV₁/PEF) were used to assess upper airway obstruction and were higher in children with BPD than asthma (P = 0.0001 and P = 0.035, respectively). We conclude that pulmonary function of children with BPD who are still symptomatic after 5 years of age is different from age-matched children with asthma, and the children with BPD demonstrate significant inspiratory flow limitations. Pediatr Pulmonol. 1998;26:167–172. © 1998 Wiley-Liss, Inc.     

Utility of bronchodilator response for asthma diagnosis in Latino preschoolers

BackgroundAsthma diagnosis in preschoolers is mostly based on clinical evidence, but a bronchodilator response could be used to help confirm the diagnosis. The objective of this study is to evaluate the utility of bronchodilator response for asthma diagnosis in preschoolers by using spirometry standardised for this specific age group.MethodsA standardised spirometry was performed before and after 200 mcg of salbutamol in 64 asthmatics and 32 healthy control preschoolers in a case-control design study.ResultsThe mean age of the population was 4.1 years (3–5.9 years) and 60% were females. Almost 95% of asthmatics and controls could perform an acceptable spirometry, but more asthmatics than controls reached forced expiratory volume in one second (FEV₁) (57% vs. 23%, p = 0.033), independent of age. Basal flows and FEV₁ were significantly lower in asthmatics than in controls, but no difference was found between groups in forced vital capacity (FVC) and FEV in 0.5 s (FEV_0.5). Using receiver operating characteristic (ROC) curves, the variable with higher power to discriminate asthmatics from healthy controls was a bronchodilator response (% of change from basal above the coefficient of repeatability) of 25% in forced expiratory flow between 25% and 75% (FEF_25–75) with 41% sensitivity, 80% specificity. The higher positive likelihood ratio for asthma equalled three for a bronchodilator response of 11% in FEV_0.5 (sensitivity 30%, specificity 90%).ConclusionsIn this sample of Chilean preschoolers, spirometry had a very high performance and bronchodilator response was very specific but had low sensitivity to confirm asthma diagnosis.     

What is the difference between FEV1 change in percentage predicted value and change over baseline in the assessment of bronchodilator responsiveness in patients with COPD?

Background

Several criteria are clinically applied in the assessment of significant bronchodilator responsiveness in chronic obstructive pulmonary disease (COPD). The present study aimed to investigate the differences in various degree of severity of COPD among these criteria.

Methods

After 400 micrograms of salbutamol administered via spacer by metered dose inhaler (MDI), forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) changes (including percentage change, absolute change and absolute change in percentage predicted value) were retrospectively analysed in 933 stable patients with mild-to-very-severe COPD. Significant bronchodilator responsiveness was assessed using American Thoracic Society and European Respiratory Society (ATS-ERS) criterion based on FEV₁ or/and FVC (both ≥12% increase over baseline and ≥200 mL) and FEV₁ percentage predicted criterion (≥10% absolute increase in percentage predicted FEV₁) in different grades of COPD.

Results

Of the patients [age 66.8 years, baseline FEV₁ 974 mL (39.3% predicted) and FVC 2,242 mL], mean improvements were 126 mL in FEV₁ and 265 mL in FVC; 21.4% and 45.3% met ATS-ERS criterion based on FEV₁ and FVC, respectively; and 13.5% met FEV₁ percentage predicted criterion. The responsive ratios of ATS-ERS criterion based on FEV₁ to FEV₁ percentage predicted criterion in grade I, II, III and IV of COPD were 0.95^:1.26^:2.53^:6.00, respectively (P<0.01 in grade II and P<0.001 in grade III). As the degree of severity increased, the mean improvement of FEV₁ was reduced; on the contrary, that of FVC was increased.

Conclusions

Compared with FEV₁ percentage predicted criterion, ATS-ERS criterion based on FEV₁ as well as FVC, the later in particular, detected a larger percentage of patients with significant responsiveness. The increasing difference was relevant as a function of the severity of airflow obstruction.KEY WORDS : Airflow obstruction, bronchodilator responsiveness, chronic obstructive pulmonary disease (COPD), forced vital capacity (FVC), forced expiratory volume in one second (FEV₁)     

Spirometric pulmonary function parameters of healthy Chinese children aged 3–6 years in Taiwan

Spirometry is a well‐known technique for evaluating pulmonary function, but few studies have focused on preschool children. The aim of this study was to determine reference values of forced spirometric parameters in young Chinese children, aged 3–6 years, in Taiwan. Spirometric measurements were performed at day care centers by experienced pediatricians. Of 248 children without a history of chronic respiratory illness, at least two valid spirometric attempts were obtained from 214 children (109 boys and 105 girls; age: 36–83 [mean = 61] months; height: 90–131 [mean = 111] cm). Values of forced expiratory volume in 1 sec (FEV₁) and 0.5 sec (FEV_0.5), forced vital capacity (FVC), peak expiratory flow rate (PEF), forced expiratory between 25% and 75% FVC (FEF_25–75), and forced expiratory flow rate at 25%, 50%, and 75% of FVC (FEF₂₅, FEF₅₀, and FEF₇₅) were derived and analyzed. There were significant positive correlations between study parameters and body height, body weight, and age. Height was the most consistently correlated measurement in both boys and girls. Although boys tended to have higher spirometric values than girls, we found significant differences only in FVC and FEV₁ between boys and girls aged 6 years. The regression equations of each parameter were obtained. In conclusion, spirometric pulmonary function tests are feasible in 3‐ to 6‐year‐old children. The obtained values and regression equations provide a reference for Chinese preschool children and may be of value in evaluating pulmonary function of children with respiratory problems in this age group. Pediatr Pulmonol. 2009; 44:676–682. © 2009 Wiley‐Liss, Inc.     

Exhaled Carbon Monoxide in Asthmatic Adults with Bronchial Reactivity: A Prospective Study

Hypothesis. We hypothesized that eCO may permit non-invasive assessment of disease activity in adults with asthma and bronchial reactivity. Methods. A total of 209 participants 18 to 65 years of age with a diagnosis of asthma and bronchial reactivity provided data for analysis. The association between eCO and bronchial reactivity, forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), peak expiratory flow rate measurements (PEFR), asthma symptoms score, and bronchodilator use cross-sectionally and within-subject change in eCO were analyzed in relation to change in these variables over 6 weeks. Results. There was no difference in eCO in those who were taking inhaled corticosteroids and those who were not (p = 0.33). There was also no cross-sectional or within-in subject association between eCO and bronchial reactivity, FEV₁, FVC, PEFR, symptoms score, or bronchodilator use. Conclusions. In a population of adults with bronchial reactivity, eCO has no or very limited potential as a biomarker of asthma activity.     

Mouthpiece Versus Facemask for Delivery of Nebulized Salbutamol in Exacerbated Childhood Asthma

We compared the bronchodilator response to salbutamol (albuterol) delivered by a compressed air nebulizer through a mouthpiece and via a facemask in 18 asthmatic children, to determine the most appropriate delivery method. Patients using a mouthpiece had significantly better mean percent increases in forced expiratory volume in 1 sec (FEV₁) and in forced vital capacity (FVC) than those using a facemask 30 min after inhalation (FEV₁: 56.4 ± 32.6 % vs. 28.9 ± 19.1%, FVC: 34.4 ± 26.4% vs. 7.5 ± 14.9%, respectively). Nebulized therapy plays an important role in the management of bronchial asthma in children and should be delivered by a mouthpiece whenever possible in cases of exacerbated asthma.     

Bronchodilator reversibility in Australian adults with chronic obstructive pulmonary disease

Abstract Background and aims: Bronchodilator reversibility (BDR) and inhaled corticosteroid (ICS) use were assessed for volunteers who responded to an advertisement requesting current or ex‐smokers who were experiencing breathlessness to attend for lung function testing. Methods: One hundred and fifty‐four volunteers responded. Forced expiratory volume (FEV₁) was measured before and after 400 µg of salbutamol. Significant BDR was assessed according to guidelines of: (i) the American Thoracic Society (≥12% plus 200 mL of baseline FEV₁ or forced vital capacity), (ii) the British ­Thoracic Society (BTS) (≥15% plus 200 mL of baseline FEV₁), (iii) the European Thoracic Society (≥10% predicted FEV₁), and (iv) the most commonly used criteria in Australia and New Zealand (≥15% of baseline FEV₁). Results: One hundred and twenty‐three subjects (33 female; 40 current smokers; median pack years 48 (range 5?144)) were suitable for analysis (i.e. had no history of asthma, demonstrable airflow limitation and a forced expiratory ratio (FER) of <70%). Twenty (16%) patients had an FEV₁ within the normal range but FER of <70%, 24 (20%) patients had mild disease (FEV₁ 60?80% predicted), 31 (24%) patients had moderate disease (FEV₁ 40?59% predicted), and 48 (39%) patients had severe disease (FEV₁ <40% predicted), according to BTS criteria. Significant BDR was evident in: (i) 58 (47%) subjects by American criteria, (ii) 26 (21%) subjects by British criteria, (iii) 19 (15%) subjects by European criteria and (iv) 36 (29%) subjects by Australasian criteria. ICS use was reported by 71 (58%) subjects overall and was weakly, but significantly, related to poorer FEV₁ (r = ?0.2; P < 0.01), and greater BDR (r = 0.3; P < 0.005). Conclusion: Chronic obstructive pulmonary disease in Australian volunteers with no history of asthma encompasses many individuals with significant BDR. Interestingly, most volunteers reported ICS use and this was related to poorer spirometry and greater BDR. However, until the underlying immuno­pathology has been determined they cannot be assumed to have ‘asthma’ or even an ‘asthmatic element’. (Intern Med J 2003; 33: 572?577)     

Pulmonary function between 6 and 18 years of age

Pulmonary function of children aged 6–18 years is described based on 82,462 annual measurements of forced vital capacity (FVC), forced expired volume in 1 second (FEV₁), and forced expiratory flow between 25% and 75%of FVC (FEF_25–75%) from 11,630 white children and 989 black children. Median height, FVC, FEV₁ FEV₁/FVC₁ and FEF_25–75% for each 3 months of age are compared among race and sex subgroups. Race— and sex-specific percentile distributions of FVC, FEV₁, FEV₁/FVC, and FEF_25—75% are presented for each centimeter of height (growth curves). For the same height, boys have greater lung function values than girls, and whites have greater ones than blacks. Lung function increases linearly with age until the adolescent growth spurt at about age 10 years in girls and 12 in boys. The pulmonary function vs. height relationship shifts with age during adolescence. Thus, a single equation or the pulmonary function-height growth chart alone does not completely describe growth during the complex adolescent period. Nevertheless, race- and sex-specific growth curves of pulmonary function vs. height make it easy to display and evaluate repeated measures of pulmonary function for an individual child. Race-, sex-, and age-specific regression equations based on height are provided, which permit the evaluation of growth during adolescence with improved accuracy and, more importantly, in comparison with previous observations for the same child. © 1993 Wiley-Liss, Inc.     

Reversible airway obstruction in rheumatic mitral valve disease

Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV₁)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β₂ agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β₂ agonist responses for FEV₁, FEV₁ as percentage of FVC (FEV₁% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max₅₀), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively.     

Ratio of waist circumference to chest circumference is inversely associated with lung function in Chinese children and adolescents

Background and objective: In White children, waist circumference (WC) is positively correlated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁). Because fat distribution differs among different races, the relationship between WC and lung function in Asian children may differ from that in White children. The present study aimed to examine the effect of WC on ventilatory function in Chinese children. Methods: A cross‐sectional study was performed on 1572 healthy subjects aged 9–18 years. Height, weight, chest circumference (CC), WC and lung function (FVC, FEV₁, peak expiratory flow (PEF) and maximal mid‐expiratory flow (MMEF)) were measured. To avoid the problem of colinearity, a model that combined CC and WC as the waist‐to‐chest ratio (WCR) was used. The relative contributions of WCR and body mass index (BMI) to spirometric parameters were determined by linear regression analysis. Results: WCR was inversely associated with all spirometric parameters. On average, each 0.01 increase in WCR was associated with decreases of 8.14 mL for FVC, 9.36 mL for FEV₁, 6.54% for FEV₁/FVC, 19.81 mL/s for PEF and 17.25 mL/s for MMEF. BMI was positively associated with all spirometric parameters except FEV₁/FVC. These results suggest that WC was inversely associated with lung function parameters. Conclusions: Inverse associations were identified between WCR, as well as WC, and lung function in a population of Chinese children. The underlying mechanisms need to be further explored.     

Effects of posture on lung function in obese children

Forced expiratory manoeuvres are recommended performed in sitting posture; however, standing posture has been reported to be usually more advantageous since any diaphragmatic restriction associated with obesity is reduced. Information on the effect of posture on forced expiratory manoeuvres in obese children is lacking. Aim: To determine whether lung function measured in standing compared with sitting posture is increased in overweight and obese children. Methods: One hundred fifteen overweight (n = 23) and obese (n = 92) children (7–17 years old) performed forced expiratory flow‐volume manoeuvres in sitting and standing posture in random order. Results: Forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and forced expiratory flow after 50% of FVC (FEF₅₀) was significantly higher in sitting compared with standing posture [0.8, 1.1 and 2.2 percentage change in absolute values (all with P < 0.05)]. FEV₁/FVC and peak expiratory flow were not significantly different measured in sitting and standing posture; 95%–99% of the variance were explained by differences among individuals (all with P < 0.0001). Conclusions: In conclusion, FEV₁, FVC and FEF₅₀ were all significantly higher when measured in sitting compared with standing posture; however, the improvements were of little clinical significance. These findings confirm that sitting posture is appropriate in obese children when performing forced expiratory flow‐volume manoeuvres. Please cite this paper as: Berntsen B, Edvardsen E, Carlsen K‐H, Kolsgaard MLP and Carlsen KCL. Effects of posture on lung function in obese children. Clin Respir J 2011; 5: 252–257.     

Airway Responsiveness to Beta‐Adrenergic Agonist (Salbutamol) in Asthma

Despite the controversy of airway responsiveness to β₂‐agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other β₂‐agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV₁), (PC₂₀) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV₁, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC₂₀ salbutamol and PC₂₀ histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC₂₀ = 7.24 mg/L) than in non‐asthmatics (PC₂₀ = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC₂₀ = 0.18 g/L) was also significantly greater than in normal subjects (PC₂₀ = 19.46 g/L, p < 0.001). There was a significant correlation between PC₂₀ salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration‐response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.     

Effect of bronchodilatation on single breath pulmonary uptake of carbon monoxide in chronic obstructive pulmonary disease

We studied 21 COPD patients in stable clinical conditions to evaluate whether changes in lung function induced by cumulative doses of salbutamol alter diffusing capacity for carbon monoxide (DL_CO), and whether this relates to the extent of emphysema as assessed by high resolution computed tomography (HRCT) quantitative analysis. Spirometry and DL_CO were measured before and after cumulative doses of inhaled salbutamol (from 200 μg to 1000 μg). Salbutamol caused significant increments of forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and flows at 30% of control FVC taken from both partial and maximal forced expiratory maneuvers. Functional residual capacity and residual volume were reduced, while total lung capacity did not change significantly. DL_CO increased progressively with the incremental doses of salbutamol, but this became significant only at the highest dose (1000 μg) and was independent of the extent of emphysema, as assessed by radiological parameters. No significant changes were observed in CO transfer factor (DLCO/VA) and alveolar volume (VA). The results suggest that changes in lung function induced by cumulative doses of inhaled salbutamol are associated with a slight but significant increase in DL_CO irrespective of the presence and extent of emphysema.     

Acute Effect of Bronchodilator on Intrathoracic Airway Wall Compliance in COPD Patients

Purpose

In patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV₁) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV₁ changes.

Methods

In a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group.

Results

Lower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72?±?0.20 ml/cmH₂O and 1.08?±?0.20 ml/cmH₂O, respectively) as compared to controls (2.28?±?0.27 ml/cmH₂O and 1.44?±?0.22 ml/cmH₂O, respectively) (p?<?0.001). In COPD patients, AWC increased significantly at both lung volumes after salbutamol, amounting to 1.81?±?0.38 ml/cmH₂O and 1.31?±?0.39 ml/cmH₂O, respectively (p?<?0.01), but the relative change was not different from that observed in controls.

Conclusion

In COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV₁ changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.