Bronchodilator Response In Patients Research Articles

Bronchodilator Response in Post-COVID-19 Patients Undergoing Pulmonary Rehabilitation

Introduction: SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. Methods: In our study, we have examined 134 post-COVID patients (aged 54.83 ± 14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. Results: Prior to bronchial dilation, 6 out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score = −1.645) indicative of an obstructive airway disease. Following inhalation of a β2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (>200 mL ΔFEV1 and >12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. Conclusion: Our data provide evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted β2-inhalation therapy including subsequent reevaluation.

Prevalence of airway reversibility in connective tissue disease-interstitial lung disease (CTD-ILD)

Background: Spirometry is the most reproducible and objective measurement of airflow limitation. Improvement in FEV1 and/or FVC by 12% or 200ml after using bronchodilator is definitive of reversible airway disease.[1] Several conditions like sarcoidosis predominantly involve the interstitium have nevertheless been associated with reversible airways obstruction. Connective tissue diseases (CTDs) form another important subgroup of interstitial lung disease(ILD). CTDs usually produce a restrictive pattern of lung involvement on spirometry, but might have unrecognized additional reversible airway obstruction. Seeking out and treating the latter components of disease may be crucial in optimizing lung function and alleviating the breathlessness that is common to the problem. Aim: The aim of this study is therefore to determine the post bronchodilator response in patients with connective tissue disease related interstitial lung disease (CTD-ILD) and thus potentially help improve quality of life by addressing the latter component by inhaled bronchodilator-steroid therapy. Methods: Consecutive patients with a confirmed diagnosis of CTD-ILD were identified in the out-patient clinics of our institute. CTD was diagnosed by a combination of clinical and serological parameters. ILD was confirmed by high resolution computed tomography (HRCT) images. 

Bronchodilator Response in Patients with COPD, Asthma-COPD-Overlap (ACO) and Asthma, Evaluated by Plethysmographic and Spirometric z-Score Target Parameters.

BackgroundAirflow reversibility criteria in COPD are still debated – especially in situations of co-existing COPD and asthma. Bronchodilator response (BDR) is usually assessed by spirometric parameters. Changes assessed by plethysmographic parameters such as the effective, specific airway conductance (sGeff), and changes in end-expiratory resting level at functional residual capacity (FRCpleth) are rarely appreciated. We aimed to assess BDR by spirometric and concomitantly measured plethysmographic parameters. Moreover, BDR on the specific aerodynamic work of breathing (sWOB) was evaluated.MethodsFrom databases of 3 pulmonary centers, BDR to 200 g salbutamol was retrospectively evaluated by spirometric (∆FEV1 and ∆FEF25–75), and plethysmographic (∆sGeff, ∆FRCpleth, and ∆sWOB) parameters in a total of 843 patients diagnosed as COPD (478 = 57%), asthma-COPD-overlap (ACO) (139 = 17%), or asthma (226 = 27%), encountering 1686 BDR-measurement-sets (COPD n = 958; ACO n = 276; asthma n = 452).ResultsEvaluating z-score improvement taking into consideration the whole pre-test z-score range, highest BDR was achieved by combining ∆sGeff and ∆FRC detecting BDR in 62.2% (asthma: 71.4%; ACO: 56.7%; COPD: 59.8%), by ∆sGeff in 53.4% (asthma: 69.1%; ACO: 51.6%; COPD: 47.4%), whereas ∆FEV1 only distinguished in 10.6% (asthma: 21.8%; ACO: 18.6%; COPD: 4.2%). Remarkably, ∆sWOB detected BDR in 49.4% (asthma: 76.2%; ACO: 47.8%; COPD: 46.9%).ConclusionBDR largely depends on the pre-test functional severity and, therefore, should be evaluated in relation to the pre-test conditions expressed as ∆z-scores, considering changes in airway dynamics, changes in static lung volumes and changes in small airway function. Plethysmographic parameters demonstrated BDR at a significant higher rate than spirometric parameters.

Role of Forced Expiratory Volume in Third second (FEV3) as An Alternative to Forced Vital Capacity (FVC) in Assessing Bronchodilator Response in Patients with Chronic Obstructive Airway Diseases

Background: Spirometry is a physiological procedure used as a diagnostic tool for disease diagnosis; e.g. obstructive pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD). The bronchodilator test is a method of measuring lung capacity changes following inhalation of a short-acting bronchodilator drug that dilates the airway, this test helps to diagnose, evaluate and differentiate asthma from COPD. Objective: To evaluate the role of forced expiratory volume in third second (FEV3) as an alternative for forced vital capacity (FVC) in assessing bronchodilator response in patients with chronic obstructive airway diseases. Methods: The study a case-control, comparative study done from November 2018 to November 2019. The cases involved divided into 2 groups; patients group included (80) patients with chronic obstructed pulmonary diseases (asthma and COPD) and control group included (160) apparently healthy peoples aged and sex matched. Lung function was measured using a standard protocol and electronic table spirometry. Bronchodilator test was done for each patient with chronic obstructed defect on spirometer. Results: There was no significant difference between (FVC), FVC% and (FEV3), FEV3% respectively before bronchodilator and there was no significant difference after bronchodilator in patients. There was no significant difference between FEV1/FVC, FEV1/FVC % and FEV1/ FEV3, FEV1/FEV3% respectively before bronchodilator and there was no significant difference after bronchodilator in patients. Conclusion: FEV3 can be used as an alternative to FVC in patients with chronic obstructive airway diseases for assessing bronchodilator response. Keywords: Spirometry, Bronchodilator test, FVC%, FEV3%, FEV1/FVC%, FEV1/FEV3% Citation: Jizar AY, Hashim ZH, Jasim AH. Role of forced expiratory volume in third second (FEV3) as an alternative to forced vital capacity (FVC) in assessing bronchodilator response in patients with chronic obstructive airway diseases. Iraqi JMS. 2020; 18(2): 94-100. doi: 10.22578/IJMS.18.2.2

Correlations of forced oscillometric bronchodilator response with airway inflammation and disease duration in asthma.

Airway resistance and reactance, measured by forced oscillometry, are used to measure the airway obstruction in patients with asthma. This study aimed to investigate the oscillometric bronchodilator responses in treated and untreated asthma and evaluate its association with airway inflammation and disease duration. This study included 30 nonsmoking patients with mild to moderate treated asthma, 25 patients with newly diagnosed untreated asthma and 29 control subjects. Spirometric and oscillometric measurements were performed before and after inhalation of 400µg salbutamol. Disease duration was defined as the number of years since asthma diagnosis. At airway resistance of 5Hz (R5) and 20Hz (R20), bronchodilator responses in patients with untreated and treated asthma were greater than those in control subjects. In patients with untreated asthma, higher fractional exhaled nitric oxide concentration (FeNO) levels were strongly correlated with greater reversibility of R20 (rs =-0.621, P< 0.001). In patients with treated asthma, there was no significant association between FeNO and oscillometric reversibility, whereas longer disease duration was significantly associated with lesser bronchodilator response at R20 (rs =0.441, P< 0.05). Treated asthma patients with longer disease duration (≥10years) showed significantly higher post-bronchodilator R5 and R20 than the treated asthma patients with shorter disease duration (<10years). The present study provides further evidence of an association between airway inflammation and variable airway obstruction in asthma patients and indicates that long-term disease duration could be related to poorly reversible airway resistance in patients with mild to moderate asthma.

Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P=0.028) but not African Americans (0.49%, P=0.426) or Puerto Ricans (0.16%, P=0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.

ADRB2 gene polymorphism and emphysema heterogeneity can modulate bronchodilator response in patients with emphysema

BackgroundGenetic variation in the β2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to β2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients. We hypothesized that differences in emphysema distribution and heterogeneity may have masked significant alterations of the bronchodilator response among ADRB2 genotypes in COPD patients in previous studies. MethodsThe BDR (induced by 20 μg of procaterol) was measured in 211 patients who had a smoking history of more than 10 pack/years and had undergone chest high resolution computed tomography examination. A low attenuations area (<960 Hounsfield Units) was identified and the emphysema heterogeneity index (EHI%) was calculated with a range in value from −100% to 100%. ADRB2 Arg16Gly genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. ResultsThe BDR was augmented in patients with homogenous emphysema compared with those with upper-dominant emphysema. In patients carrying the AA genotype of ADRB2, the BDR was significantly increased in patients with upper-dominant emphysema, but not in patients with lower-dominant emphysema. ConclusionCombination analysis of ADRB2 Arg16Gly polymorphism and EHI% may predict the effectiveness of β2-adrenergic receptor agonist treatment in patients with COPD and emphysema.

Efficiency of neural respiratory drive for the assessment of bronchodilator responsiveness in patients with chronic obstructive pulmonary disease: an exploratory study.

Conventional lung function parameters, such as forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC) are often used to assess the therapeutic outcomes of bronchodilators, but they lack sensitivity. A novel indicator, namely efficiency of neural respiratory drive (NRD), may objectively evaluate the physiological changes in patients with chronic obstructive pulmonary disease (COPD). We investigated whether this indicator could be used to more accurately assess the responsiveness to inhaled bronchodilators. Thirty-six subjects with moderate-to-severe COPD were randomized into group A (n=18) and group B (n=18). Participants in group A inhaled 400 µg placebo, 400 µg salbutamol and 80 µg ipratropium in sequence whereas those in group B had the salbutamol and ipratropium reversed. At different time points after administration of placebo or bronchodilators, evaluated indices included FEV1, FVC, IC, root mean square (RMS) of diaphragm electromyogram (EMGdi), and efficiency of NRD [herein defined as the ratio of minute ventilation (VE) to RMS, or VE/RMS]. FEV1, FVC, IC, RMS, and VE/RMS significantly improved after inhaled bronchodilators and VE/RMS had the largest improvement among five indices. The detection efficiency of VE/RMS was greater than FEV1, FVC, IC (all P<0.05), but not different from RMS. The accuracy and sensitivity of VE/RMS were significantly higher than FEV1, FVC, IC, and RMS (all P<0.05). Efficiency of NRD may be a sensitive tool to evaluate the efficacy of inhaled bronchodilators in COPD.

Efficiency of Neural Respiratory Drive for the Assessment of Bronchodilator Responsiveness in Patients With Chronic Obstructive Pulmonary Disease: An Exploratory Study

Efficiency of Neural Respiratory Drive for the Assessment of Bronchodilator Responsiveness in Patients With Chronic Obstructive Pulmonary Disease: An Exploratory Study

Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

BackgroundWe investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD).MethodsWe studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured. Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs).ResultsEighty out of 100 participants had R5 – R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 – R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons). Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation.ConclusionThis study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1.

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?

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. 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. 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. 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.

Bronchodilator responsiveness in patients with chronic heart failure

ObjectiveThe aim of this study was to evaluate the effect of inhaled bronchodilators on pulmonary function and dyspnea in patients with chronic heart failure (HF). BackgroundConflicting data exist on whether bronchodilators may improve pulmonary function and dyspnea in patients with chronic HF. MethodsIn this retrospective observational study we analyzed data of 116 chronic HF outpatients with systolic dysfunction who underwent spirometry and Borg dyspnea measurements before and after inhalation of 400 μg salbutamol and 80 μg ipratropium. Patients with chronic obstructive pulmonary disease (COPD) or asthma were excluded. ResultsBronchodilators fully reversed airway obstruction (AO) in 25 of 64 (39.1%) patients with pre-bronchodilator AO. All spirometric measurements, except for forced vital and inspiratory capacities, improved significantly post-bronchodilation. Absolute and percent improvements in forced expiratory volume in 1 s (FEV1) were more pronounced in patients with persistent AO post-bronchodilation compared to those without AO (0.19 ± 0.18 L and 8.4 ± 7.3% versus 0.11 ± 0.12 L and 4.3 ± 4.0%, p < 0.05). Significant bronchodilator responsiveness of FEV1 (>200 mL and >12%) was noted in 12.1% and was more frequent in patients with persistent AO and fully reversible AO than in those without AO (23.1% and 16.0% versus 1.9%, p < 0.05). We measured a small, albeit significant improvement in dyspnea (0.7 ± 1.2 versus 0.9 ± 1.3, p = 0.002). ConclusionsInhaled bronchodilators may have an additional role in the management of patients with chronic HF because of their potential to improve pulmonary function, especially in those with AO. The clinical usefulness and possible adverse events of bronchodilators need to be further established.

Bronchodilator Response in Patients With Normal Baseline Spirometry

Spirometry before and after bronchodilator is performed to assess air flow-limitation reversibility. In patients with normal baseline spirometry the frequency of a positive bronchodilator response, as defined by American Thoracic Society/European Respiratory Society criteria, has not been described. We retrospectively analyzed adult patients tested in 2 academic pulmonary function testing laboratories over a 7-year period, with specific attention to patients who underwent bronchodilator testing after a normal baseline spirometry (FEV(1), FVC, and FEV(1)/FVC within normal limits). The frequency of a positive response to bronchodilator, defined as a 12% and 200 mL increase in either FEV(1) or FVC, was calculated and associated with demographic factors. Of the 1,394 patients with normal spirometry who were administered bronchodilator, 43 (3.1%) had a positive response. The percent of patients responding to bronchodilator were grouped according to pre-bronchodilator FEV(1): > lower limit of normal to 90% of predicted = 6.9%, 90-100% of predicted = 1.9%, and > 100% of predicted = 0%. An FEV(1)/FVC in the lowest 2 quartiles was associated with a higher frequency of bronchodilator response. Older patients were more likely to respond to bronchodilator, but no other demographic factors were associated with a positive bronchodilator response. In our study population the frequency of a positive bronchodilator response in patients with normal baseline spirometry is 3.1%. None of the patients with a pre-bronchodilator FEV(1) > 100% of predicted and only 1.9% of patients with an FEV(1) between 90% and 100% of predicted responded. Bronchodilator testing can be omitted in patients with normal spirometry and an FEV(1) above 90% of predicted, as they have a low probability of a positive response.

Comparison of bronchodilator response in patients with asthma and healthy subjects using spirometry and oscillometry

Impulse oscillometry (IOS) is an effort-independent and patient-friendly pulmonary function technique, but limited data are available that correlate the bronchodilator response using spirometry and IOS in adult asthmatic and healthy subjects. To compare spirometry and IOS in ongoing bronchodilator response. The study was a prospective evaluation of patients with asthma and healthy subjects attending screening at a research unit in a university teaching hospital. Reversibility testing was carried out using standardized American Thoracic Society/European Respiratory Society (ATS/ERS) criteria after administering 400 μg salbutamol by AccuhalerTM. Impulse oscillometry measurements (resistance at 5 Hz [R5], resistance at 20 Hz [R20], reactance at 5 Hz [X5]) and spirometry (forced expiratory volume in 1 second [FEV(1)], forced vital capacity [FVC], forced expiratory flow from 25% to 75% of vital capacity [FEF(25-75)]) were recorded pre and postbronchodilator. Ninety-five asthmatic and 61 healthy subjects underwent screening. Mean percent (standard error of the mean [SEM]) baseline prebronchodilator FEV(1) was 83.99 (2.23) for patients with asthma, and 99.25 (1.72) for healthy subjects. Baseline percent predicted IOS indices in the group with asthma were 162.22 (7.5) for R5; 154.73 (4.71) for R20; and 441.72 (173.86) for X5. In healthy volunteers, corresponding values were 111.01 (3.96), 127.75 (4.12), and -229.80 (125.75). R5 was the only IOS measure that showed correlation with spirometry (FEV(1)) in both groups. The mean percent (SEM) predicted postbronchodilator change in FEV(1) and R5 in patients with asthma was 6.35 (0.65) and -33.78 (4.43); correspondingly in healthy subjects it was 2.24 (0.32) and -14.91 (2.48). A negative correlation was demonstrated (r = -0.40, P < .001 between the 2 indices in patients with asthma. Linear regression modeling demonstrated that 1 unit change in %FEV(1) corresponds to a 2.5% change in %R5. Low-frequency IOS as R5 and spirometry as FEV(1) correlate in patients with asthma and healthy subjects, with changes that can be predicted by linear regression.

Bronchodilator responsiveness and onset of effect with budesonide/formoterol pMDI in COPD

Chronic obstructive pulmonary disease (COPD) patients are thought to have limited bronchodilator response, determined by changes in forced expiratory volume in 1s (FEV(1)). In this study, we assessed bronchodilator response in patients with COPD using not only FEV(1) but also changes in lung volume expressed as forced vital capacity (FVC) and inspiratory capacity (IC). We also evaluated the speed of onset of bronchodilation. Data were from 2 randomized, double-blind, placebo-controlled studies (6-months [NCT00206154]; 12-months [NCT00206167]) in patients with moderate to very severe COPD. twice daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) 320/9μg, budesonide/formoterol pMDI 160/9μg, formoterol dry powder inhaler (DPI) 9μg, placebo. The percentage of patients with FEV(1) improvement (≥12% and ≥200mL; American Thoracic Society [ATS] criterion) was 34-39% post-albuterol (screening). On day of randomization (DOR), a larger proportion receiving formoterol-containing treatment exhibited reversibility within 60min: FEV(1) (57-59%). Similar results were seen for IC (50-61%) and FVC(57-67%) using the same improvement criteria. The time to ≥15% FEV(1) improvement on DOR was 5.0, 4.8, and 7.3min for budesonide/formoterol 320/9, budesonide/formoterol 160/9, and formoterol, respectively. Time to ≥15% FEV(1) improvement was better maintained with budesonide/formoterol than formoterol at treatment end (6 and 12 months). Most patients with moderate to very severe COPD exhibit ATS-defined bronchodilator reversibility based on flow and lung volume measures after budesonide/formoterol pMDI or formoterol treatment. Budesonide/formoterol pMDI also has a rapid (within 5min) onset of bronchodilation that is maintained over time compared with formoterol alone.

Prediction of Brobchodilator Response by Using FEF25~75%in Adult Patient with a Normal Spirometry Result

commonly used, because of its high individual variability. We evaluated the pattern of bronchodilator responsiveness (BDR) and the correlation between FEF 25∼75% and BDR in patients with suspicious asthma and normal spirometry. Methods: Among patients with suspicious bronchial asthma, 440 adult patients with a normal spirometry result (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] ≥70% & FEV1% predicted ≥80%) were enrolled. We divided this group into a positive BDR group (n=43) and negative BDR group (n=397), based on the result of BDR. A comparison was carried out of spirometric parameters with % change of FEV 1 after bronchodilator (ΔFEV1%). Results: Among the 440 patients with normal spirometry, FEF25∼75%% predicted were negatively correlated with ΔFEV1% (r=−0.22, p＜0.01), and BDR was positive in 43 patients (9.78%). The means of FEF25∼75%% predicted were 64.0±14.5% in the BDR (＋) group and 72.9±20.8% in the BDR (−) group (p＜0.01). The negative correlation between FEF25∼75%% predicted and ΔFEV1% was stronger in the BDR (＋) group (r=−0.38, p=0.01) than in the BDR (−) group (r=−0.17, p＜0.01). In the ROC curve analysis, FEF25∼75% at 75% of predicted value had 88.3% sensitivity and 40.3% specificity for detecting a positive BDR. Conclusion: BDR (＋) was not rare in patients with suspicious asthma and normal spirometry. In these patients, FEF25∼75%% predicted was well correlated with BDR.

Bronchodilator responsiveness in patients with COPD

The degree of acute improvement in spirometric indices after bronchodilator inhalation varies among chronic obstructive pulmonary disease (COPD) patients, and depends upon the type and dose of bronchodilator and the timing of administration. Acute bronchodilator responsiveness at baseline was examined in a large cohort of patients with moderate-to-very-severe COPD participating in the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, a 4-yr randomised double-blind trial evaluating the efficacy of 18 mug tiotropium daily in reducing the rate of decline in lung function. After wash-out of respiratory medications, patients received 80 mug ipratropium followed by 400 mug salbutamol. Spirometry was performed before and 90 min following ipratropium administration. The criteria used for forced expiratory volume in one second (FEV(1)) responsiveness were: >or=12% increase over baseline and >or=200 mL; >or=15% increase over baseline; and >or=10% absolute increase in the percentage predicted value. Of the patients, 5,756 had data meeting the criteria for analysis (age 64.5 yrs; 75% male; baseline FEV(1) 1.10 L (39.3% predicted) and forced vital capacity (FVC) 2.63 L). Compared with baseline, mean improvements were 229 mL in FEV(1) and 407 mL in FVC. Of these patients, 53.9% had >or=12% and >or=200 mL improvement in FEV(1), 65.6% had >or=15% improvement in FEV(1), and 38.6% had >or=10% absolute increase in FEV(1) % pred. The majority of patients with moderate-to-very-severe chronic obstructive pulmonary disease demonstrate meaningful increases in lung function following administration of inhaled anticholinergic plus sympathomimetic bronchodilators.

Bronchodilator response in patients with persistent allergic asthma could not predict airway hyperresponsiveness.

Anticholinergics, or specific antimuscarinic agents, by inhibition of muscarinic receptors cause bronchodilatation, which might correlate with activation of these receptors by the muscarinic agonist methacholine. The aim of this study was to determine whether a positive bronchodilator response to the anticholinergic ipratropium bromide could predict airway hyperresponsiveness in patients with persistent allergic asthma. The study comprised 40 patients with mild and moderate persistent allergic asthma. Diagnosis was established by clinical and functional follow-up (skin-prick test, spirometry, bronchodilator tests with salbutamol and ipratropium bromide, and methacholine challenge testing). The bronchodilator response was positive to both bronchodilator drugs in all patients. After salbutamol inhalation, forced expiratory volume in 1 second (FEV1) increased by 18.39 ± 6.18%, p < .01, whereas after ipratropium bromide, FEV1 increased by 19.14 ± 6.74%, p < .01. The mean value of FEV1 decreased by 25.75 ± 5.16%, p < .01 after methacholine (PC20 FEV1 [provocative concentration of methacholine that results in a 20% fall in FEV1] from 0.026 to 1.914 mg/mL). Using linear regression, between methacholine challenge testing and bronchodilator response to salbutamol, a positive, weak, and stastistically significant correlation for FEV1 was found (p < .05). Correlations between methacholine challenge testing and the bronchodilator response to ipratropium bromide were positive and weak but not statistically significant. The positive bronchodilator response to ipratropium bromide could not predict airway hyperresponsiveness.

β2-Adrenergic Receptor Genetic Polymorphisms and Short-term Bronchodilator Responses in Patients With COPD

COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the beta2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta2-agonists; however, the effects of these polymorphisms on responses to beta2-agonists in patients with COPD is unknown. To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta2-agonists in patients with COPD. A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. The presence of the Arg16 allele was associated with lower BDRs to beta2-agonist inhalation. The mean (+/-SD) log (postbronchodilator FEV1-prebronchodilator FEV1) values of Gly16 homozygotes (n=65), Arg16Gly16 heterozygotes (n=106), and Arg16 homozygotes (n=75) were 2.19+/-0.43, 2.09+/-0.42, and 2.01+/-0.42, respectively (p<0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p<0.01). The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting beta2-agonists in patients with COPD.

VARIABLE BRONCHODILATOR RESPONSE IN 6867 PULMONARY FUNCTION TESTS

PURPOSE: While performing pulmonary functions tests (PFTs), variable responses to bronchodilators have been anecdotally noted. It has been suggested that up to fifteen percent of patients with a β2-adrenoreceptor haplotype or genotype may have a negative response to inhaled bronchodilators. To date, there has been sparse literature addressing this phenomenon. This study was conducted to evaluate the distribution of bronchodilator response in patients deemed candidates for PFTs.