Significant Bronchodilator Response Research Articles

Regional lung response to bronchodilator reversibility testing determined by electrical impedance tomography in chronic obstructive pulmonary disease.

Patients with obstructive lung diseases commonly undergo bronchodilator reversibility testing during examination of their pulmonary function by spirometry. A positive response is defined by an increase in forced expiratory volume in 1 s (FEV1). FEV1 is a rather nonspecific criterion not allowing the regional effects of bronchodilator to be assessed. We employed the imaging technique of electrical impedance tomography (EIT) to visualize the spatial and temporal ventilation distribution in 35 patients with chronic obstructive pulmonary disease at baseline and 5, 10, and 20 min after bronchodilator inhalation. EIT scanning was performed during tidal breathing and forced full expiration maneuver in parallel with spirometry. Ventilation distribution was determined by EIT by calculating the image pixel values of FEV1, forced vital capacity (FVC), tidal volume, peak flow, and mean forced expiratory flow between 25 and 75% of FVC. The global inhomogeneity indexes of each measure and histograms of pixel FEV1/FVC values were then determined to assess the bronchodilator effect on spatial ventilation distribution. Temporal ventilation distribution was analyzed from pixel values of times needed to exhale 75 and 90% of pixel FVC. Based on spirometric FEV1, significant bronchodilator response was found in 17 patients. These patients exhibited higher postbronchodilator values of all regional EIT-derived lung function measures in contrast to nonresponders. Ventilation distribution was inhomogeneous in both groups. Significant improvements were noted for spatial distribution of pixel FEV1 and tidal volume and temporal distribution in responders. By providing regional data, EIT might increase the diagnostic and prognostic information derived from reversibility testing.

Bronchodilator Responsiveness and Airflow Limitation Are Associated With Deployment Length in Iraq and Afghanistan Veterans.

The aim of this study was to determine the relationship between deployment length and indices of airflow obstruction in Iraq and Afghanistan veterans with airborne hazards exposure. One hundred twenty-four post-9/11 veterans completed pulmonary function testing and questionnaires. We examined the association of airflow limitation [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)] and bronchodilator responsiveness (ΔFEV1 and ΔFVC) with deployment length, adjusting for smoking. Longer deployment length was associated with lower FEV1/FVC [β = -0.19; 95% confidence interval (95% CI), -0.39 to 0.01], greater ΔFEV1 (β = 0.27; 95% CI, 0.09 to 0.45) and ΔFVC (β = 0.19; 95% CI, 0.05 to 0.33). In our model adjusted for smoking history, longer deployment length remained associated with greater ΔFEV1 and ΔFVC (P < 0.01), but not with FEV1/FVC (P = 0.059). In our sample of post-9/11 veterans, longer deployment lengths were associated with significant bronchodilator responsiveness and a trend toward airflow limitation independent of tobacco use.

Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications.

Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs). We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov. BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test). Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort.

Alternative functional criteria to assess airflow-limitation reversibility in asthma

IntroductionInternational guidelines define significant bronchodilator response as absolute and percentage change from baseline in forced expiratory volume (FEV1) in the first second and/or forced vital capacity (FVC) ≥12% and 200mL. However, bronchodilator effects on other lung function parameters have also been correlated to some degree of reversible airflow limitation. ObjectivesTo determine whether changes in other lung function parameters apart from FEV1 and FVC detect functional responses to bronchodilator in asthmatic patients. Materials and methodsSpirometry and body plethysmography were performed at baseline conditions and after administration of 400μg of salbutamol by metered-dose inhaler through a space chamber device in asthmatic patients. Paired t-tests were used to compare lung function parameters between those with and without criteria for reversibility of airway obstruction according to ATS/ERS criteria. Cut-off values were obtained from the corresponding ROC curves. Measurements evaluated were FEV1, FVC, maximum mid-forced expiratory flow (FEF25–75%), residual volume (RV), inspiratory capacity (IC), airway resistance (Raw) and specific airway conductance (sGaw). ResultsFrom a total of 100 consecutive asthmatics patients (46% of them men; average age 58.7±14.1 years; 76% with mild to moderate obstruction), 50 patients had a significant bronchodilator response. All of these had noteworthy variations (p<0.004) in PEF, FEF25–75%, RV, Raw and sGaw. The most accurate in predicting a significant bronchodilator response were the absolute and percentage improvements in PEF (≥0.4L/s and 8%), FEF25–75% (≥0.087L/s and 27%) and the percentage of sGaw compared with that at baseline (≥25%). Based on these cut-off values, a sizeable number of the patients defined as non-responders had important changes in airway caliber. 17 patients had significant increments in the percentage of PEF and 10 had changes in absolute volume; 6 patients had increments in percentage and 16 in absolute change of FEF25–75%; 22 patients had increments in the percentage change of sGaw. ConclusionsChanges of FEV1 and/or FVC may underestimate significant functional response to bronchodilators in asthmatic patients with airway obstruction when considering the change in other lung function parameters.

Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia.

Mannose-binding lectin (MBL) plays an important role in innate immunity and has been reported to be associated with the age-related decline in lung function in cystic fibrosis. MBL polymorphisms are associated with lung function decline in Primary Ciliary Dyskinesia (PCD). We performed sputum microbiology, spirometry pre- and post-administration of salbutamol, ciliary motion analysis, ultrastructural assessment of cilia, ciliogenesis in culture, and chest high resolution computed tomography in children with a clinical history of respiratory tract infections and/or presence of bronchiectasis suggestive of PCD or secondary ciliary dyskinesia (SCD). All subjects were evaluated for single nucleotide polymorphisms in the gene encoding MBL-2. The diagnosis of PCD was established in 45 subjects, while in the remaining 53 the diagnosis was SCD. A significant bronchodilator response was observed only in PCD associated with the MBL2-3 genotype, which is known to be associated with low/undetectable MBL serum levels. Also, bronchiectasis severity was significantly greater in subjects with MBL2-3 in both PCD and SCD. No other association was found between MBL genotypes and clinical findings. MBL plays a relatively minor role as a disease modifier in PCD. A similar finding in SCD supports the likely significance of this result.

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.

Lung Volume Abnormalities and its Correlation to Spirometric and Demographic Variables in Adult Asthma

Background. Presence of airflow obstruction in asthma has been based on a fixed FEV1(forced expiratory volume at 1 second)/FVC (forced vital capacity) ratio abnormality. The accuracy of FEV1/FVC ratio in diagnosing airflow obstruction remains controversial. Lung volume abnormalities have been observed in severe asthma. We utilized simultaneously measured spirometry and lung volume to determine the utility of residual volume (RV)/total lung capacity (TLC) ratio in diagnosing airflow obstruction and to identify predictors of abnormal RV in asthmatic subjects. Methods. Data from physician-diagnosed asthmatics referred for lung function tests were collected retrospectively. Patient demographics and lung function data were analyzed using general linear modeling. Results. Of the 321 subjects, 221 were female (69%). The ethnicity was Caucasian in 157 (49%), Hispanic in 131 (41%), and African-American in 33 (10%). The percentage of subjects with FEV1/FVC ratio <70%, FEV1-predicted <80%, and FEF25–75% <65% were 25%, 25%, and 38%, respectively. Fifty-two and fifty-seven percent of the patients had abnormal residual volume and abnormal RV/TLC ratio, respectively. A significant bronchodilator response was observed in 32% of the patients. A positive correlation was observed between RV to age (r = 0.4) and height (r = 0.3). A negative correlation was observed between RV to FEF25–75% (r = 0.5) and body weight (r = 0.07). There was no significant correlation between FEV1 reversibility and residual volume (r = 0.1). RV correlated significantly better with FEF25–75% (r2 = 0.25) than FEV1 (r2 = 0.16). Conclusion. A significant proportion of asthmatic patients have elevated residual volume and abnormal RV/TLC ratio in the presence of normal FEV1/FVC ratio and absence of significant bronchodilator response. The clinical significance of these findings in asthma needs further prospective study.

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.

Sensitivity of impulse oscillometry and spirometry in beta-blocker induced bronchoconstriction and beta-agonist bronchodilatation in asthma

BackgroundImpulse oscillometry (IOS) provides an alternative method of assessing pulmonary function to conventional spirometry. ObjectiveTo compare the sensitivities of IOS and spirometry in assessing bronchoconstriction to propranolol and bronchodilation with salbutamol. MethodsA post-hoc analysis of a randomized placebo-controlled crossover study was performed. Patients with mild-to-moderate persistent stable asthma taking 1,000 μg/day or less beclomethasone dipropionate equivalent received 10 or 20 mg of oral propranolol followed by histamine challenge, with recovery to nebulized salbutamol (5 mg). Spirometry and IOS were measured before and 2 hours after beta-blocker, post histamine, and 20 minutes post-salbutamol. Pre versus post percent change (95%CI) values were compared, and standardized response means (SRM) were calculated to assess the “signal to noise” of each test. ResultsThirteen participants (mean age, 34 years) completed the protocol. Eleven participants received 20 mg of propranolol; 2 received 10 mg, because this dose caused more than 10% decrease in forced expiratory volume in 1 second (FEV1) on the test-dose algorithm. All IOS indices (R5, R5-R20, AX, RF) showed significant worsening of airways resistance or reactance to propranolol. FEV1 but not FEF25-75 showed significant deterioration after beta-blocker (mean percent change, 4.6% and 6.2%). The magnitude of change was consistently higher for parameters of IOS, with the largest change being observed with R5 and RF (mean percent change, 30.8% and 39.4%). The SRMs for IOS outcomes were better than for spirometry. All measures of lung function showed significant bronchodilator response, with the best SRMs seen in R5 and RF. ConclusionIOS is a more sensitive response outcome than spirometry with respect to bronchoconstriction to oral propranolol and bronchodilatation after salbutamol in patients with mild to moderate asthma.

Assessment of early pulmonary function abnormalities in giant omphalocele survivors

PurposeInfants with giant omphalocele (GO) are at increased risk for persistent respiratory insufficiency, yet information regarding the systematic assessment of their lung function is limited. We performed a group of pulmonary function tests (PFTs) including spirometry, fractional lung volume measurements, assessment of bronchodilator responsiveness, and passive respiratory mechanics in GO survivors during infancy and early childhood to evaluate the nature and degree of pulmonary dysfunction. Material and MethodsBetween July 2004 and June 2008, 30 consecutive GO survivors were enrolled in our interdisciplinary follow-up program. Forty-seven percent (14/30) underwent PFT during follow-up evaluation using the raised volume rapid thoracic compression technique to measure forced expiratory flows and bronchodilator responsiveness, body plethysmography to calculate lung volumes, and the single breath occlusion technique to measure passive mechanics of the respiratory system. ResultsThe mean age at PFT assessment was 19.3 ± 19.7 months (range, 1.0-58). Mean forced vital capacity and mean forced expiratory volume in the first 0.5 second were significantly reduced compared with published normative values (P = .03 and P < .01, respectively). Total lung capacity was significantly reduced (P < .001), whereas functional residual capacity, residual volume, and residual volume to total lung capacity ratio were within the normative range (P = .21, P = .34, and P = .48, respectively). Among the 46% who demonstrated significant bronchodilator responsiveness, there were greater increases in the mean percentage changes in flow at 25% to 75% (P = .01), flow at 75% (P < .001), and flow at 85% (P < .001) compared with those participants that did not respond. Specific compliance was reduced, whereas specific conductance increased, compared with published normal results. ConclusionsAbnormalities of pulmonary function in GO survivors include lung volume restriction without airway obstruction, an increased likelihood of airway hyperresponsivness, and reduced respiratory system specific compliance. Early recognition of pulmonary functional impairment in GO survivors could help to develop targeted treatment strategies to reduce the risk of subsequent pulmonary morbidity.

Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study

RationaleCriteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and...

Mast cells in COPD airways: relationship to bronchodilator responsiveness and angiogenesis

We have investigated whether mast cells are associated with bronchodilator responsiveness and airway vascular changes in chronic obstructive pulmonary disease (COPD) airways. We have previously shown that the reticular basement membrane is hypervascular and the lamina propria is hypovascular in COPD. Bronchial biopsies from 32 COPD subjects, 15 smokers with normal lung function and 17 controls, were immunostained for factor VIII, mast cell tryptase and chymase antibodies. Mast cells in the airway smooth muscle, the reticular basement membrane and the underlying lamina propria were quantitated. 41% of COPD subjects had significant bronchodilator responsiveness, but this was not related to smooth muscle mast cell numbers. The reticular basement membrane had greater mast cell density in all groups compared with controls (p<0.01). In this compartment, perivascular mast cell density was related to hypervascularity. Lamina propria mast cell density was increased only in COPD (p<0.05). Perivascular mast cell density in the lamina propria was not related to its decreased vessel density. Bronchodilator responsiveness in COPD is not related to large airway smooth muscle mast cells of either type; both reticular basement membrane and lamina propria mast cells are increased in COPD patients, and perivascular mast cells may be involved in increased angiogenesis in the reticular basement membrane.

Significant Bronchodilator Responsiveness and “Reversibility” in a Population Sample

ABSTRACTChronic Obstructive Pulmonary Disease (COPD) is defined by being “not fully reversible”, most guidelines recommend measurement of lung function after the administration of a bronchodilator. The objective of this study was to compare bronchodilator responsiveness (significant improvement in the FEV1 or FVC) to full-, partial- or “inverse’” reversibility in obstruction status in a population-based sample in Southeastern Kentucky. The study population was selected using random digit dialing of an adult population in Southeastern Kentucky as part of the Burden of Lung disease (BOLD) project. Lung function was assessed using spirometry pre- and post-bronchodilation. Subjects presence and severity of COPD was classified using modified Global Obstructive Lung Disease (GOLD) criteria. We examined the relation between changes in “obstruction” status (based on the FEV1/ FVC of 0.7) and the presence of “significant bronchodilator responsiveness” (based on ≥ 12% improvement in the FEV1 or the FVC). The final population with acceptable pre- and post-bronchodilator spirometry included 440 participants. 32/440 subjects (7.3%) changed from obstructed to unobstructed (full-reversibility), 19/440 (4.3%) changed from unobstructed to obstructed (“inverse”-reversibility), 389/440 (88.4%) had either no-change or partial-reversibility, and 65/440 (14.8%) had bronchodilator responsiveness. Among those with full-reversibility, only 9/32 (28.1%) had bronchodilator responsiveness, whereas among subjects with “inverse”-reversibility, 10/19 (52.6%) had bronchodilator responsiveness. Among all subjects with bronchodilator responsiveness, only 19/65 (29.2%) changed categories. Our findings suggest that significant bronchodilator responsiveness is not the same as “reversibility” of “obstruction”, even though these terms are often used interchangeably.

Random variation of inspiratory lung function parameters in patients with COPD: a diagnostic accuracy study

BackgroundIn chronic obstructive pulmonary disease (COPD), the response of the forced expiratory volume in 1 second (FEV1) after bronchodilator application is weak. Inspiratory parameters like the forced inspiratory volume in 1 second (FIV1) and inspiratory capacity (IC) can be responsive to bronchodilators. In an individual patient with COPD, a significant bronchodilator response must at least exceed the random variation for that parameter. Therefore, it is important that the type of scatter is homoscedastic, as the chance of underestimating or overestimating the random variation for low or high parameter values is minimized. The aim of this study is to investigate the random variation (type and quantity) of inspiratory parameters.MethodsIn 79 stable COPD patients, spirometry was performed.The forced inspiratory volume in 1 second (FIV1), inspiratory capacity (IC), maximal inspiratory flow at 50% (MIF50) and peak inspiratory flow (PIF) were measured five times in one day and again within two weeks of the first measurement. The values of these parameters, taken within one hour, within one day and between two different days, were compared. The coefficient of repeatability (CR) was calculated, and, in addition, linear regression was performed to investigate the type of scatter (homo- or heteroscedastic) of the measured parameters.ResultsThe type of scatter was heteroscedastic for all of the parameters when the differences were expressed as absolute values; however, when the differences were expressed as the percent change from the initial values, we found a more homoscedastic scatter. The CR within one hour of each parameter expressed as the percent change from the initial value was: IC, 19%; FIV1, 14%; PIF, 18%; MEF50, 21%.ConclusionsTo obtain a more homoscedastic scatter, percentage changes in FIV1, IC and MIF50 are more appropriate than absolute changes.In an individual patient with COPD, a significant improvement for a particular parameter must at least exceed the above-mentioned CR.

Comparison of the efficacy of salmeterol/fluticasone propionate combination in Japanese and Caucasian asthmatics

The effect of ethnicity on the efficacy of salmeterol (S)+fluticasone propionate (FP) has not been examined in Japanese and Caucasian asthmatics. In this study, the efficacy of combination treatment with S and FP from a single inhaler (SFC) was compared with concurrent treatment with S and FP administration from separate inhalers (S+FP) in Japanese and Caucasian asthmatics. This was a randomised, double-blind, crossover study in male and female Japanese (n=18) and Caucasian (n=17) asthmatics (50-100% predicted FEV(1); >35% reversibility in sGaw). Subjects received SFC (S 50 mcg/FP 250 mcg b.i.d.) and S+FP (S 50 mcg b.i.d.+FP 250 mcg b.i.d.) for 14 days. sGaw and FEV(1) were determined 0-12h after the first and last doses. Treatment with both SFC and S+FP produced marked bronchodilation, which was maintained 0-12h after the first dose. Baseline sGaw and FEV(1) increased up to 51% and 180 mL, respectively, in Japanese subjects over 2 weeks of treatment, with similar improvements in Caucasian subjects. On Day 14 the 0-12h S+FP:SFC treatment ratios (90% CI) for sGaw AUC and peak were 1.05 (0.98, 1.12) and 1.05 (0.97, 1.14), respectively, in Japanese subjects, and 0.99 (0.92, 1.07) and 0.98 (0.89, 1.07), respectively, in Caucasian subjects, with no difference between the two ethnic groups. The finding of a similar significant bronchodilator response in Japanese and Caucasian asthmatics following concurrent and combination treatment with salmeterol and FP suggests that the therapeutic response to these agents is comparable and independent of ethnicity in Japanese and Caucasian asthma patients.

Utilidad del VEF0,5 versus VEF1 en la interpretación de la espirometría realizada en preescolares asmáticos

Background: FEVi is not easily obtained in preschool children. Objective: To evaluate the utility ofFEV0i5 vs FEVi in the spirometry of asthmatic preschool children. Material and Methods: spirometry was performed to 39 asthmatic children and 77 controls. Each child performed maneuvers during 15 minutes without nose clip and if required a computer-animation program was used. An acceptable curve was defined as a register with evident peak expiratory flow (PEF) without sudden cessation of air flow at more than 20%> of the previously measured PEF. Results: 94%> and 90% of healthy and asthmatics performed at least two acceptable curves. Median age in healthy children was 4.7 years-old (2.5 to 5.9) and 3.8 years-old (2.3 to 5.2) in asthmatics. FEVi was obtained in 51.3% of controls and in 43% of asthmatics. In contrast FEV0.S was obtained in all the children. A significant bronchodilator response was observed in FEV0.S in 49%> of asthmatics. Conclusions: FEVo.5 was more useful than FEVi in interpreting spirometry in 3 to 5 years old children with asthma

Computational fluid dynamics can detect changes in airway resistance in asthmatics after acute bronchodilation

The effect of a bronchodilator in asthmatics is only partially described by changes in spirometric values since no information on regional differences can be obtained. Imaging techniques like high-resolution computed tomography (HRCT) provide further information but lack detailed information on specific airway responses. The aim of the present study was to improve the actual imaging techniques by subsequent analysis of the imaging data using computational fluid dynamics (CFD). We studied 14 mild to moderately severe asthmatics. Ten patients underwent HRCT before and 4 h after inhalation of a novel long acting β 2 agonist (LABA) that acts shortly after inhalation. Four patients were studied for chronic effects and underwent CT scans twice after adequate wash-out of bronchodilators. In the active group, a significant bronchodilator response was seen with a forced expiratory volume in 1 s (FEV1) increase of 8.78±−6.27%pred vs −3.38±6.87%pred in the control group. The changes in FEV1 correlated significantly with the changes in distal airway volume ( r=0.69, p=0.007), total airway resistance ( r=−0.73, p=0.003) and distal airway resistance ( r=−0.76, p=0.002) as calculated with the CFD method. The changes in distal R aw were not fully homogeneous. In some patients with normal FEV1 at baseline, CFD-based changes in R aw were still detectable. We conclude that CFD calculations, based on airway geometries of asthmatic patients, provide additional information about changes in regional R aw. All changes in the CFD-based calculated R aw significantly correlate with the observed changes in spirometric values therefore validating the CFD method for the studied application.

Chronic Cough and Dyspnea in Ice Hockey Players After an Acute Exposure to Combustion Products of a Faulty Ice Resurfacer

The aim of this study was to characterize pulmonary function and radiologic testing in ice hockey players after exposure to combustion products of a faulty ice resurfacer. Our patients were 16 previously healthy hockey players who developed chronic cough and dyspnea after exposure. Symptom questionnaires, pulmonary function tests (PFTs), bronchoprovocation testing, cardiopulmonary exercise testing, high-resolution computed tomography (CT) imaging, and impulse oscillometry (IOS) were all used. A normal group was used for PFTs and IOS controls. Patients had onset of cough within 72 h of exposure. Ninety-two percent complained of dyspnea, 75% chest pain, and 33% hemoptysis. Eight percent were initially hospitalized for their symptoms. Eighty-five percent were treated with systemic steroids and 39% with inhaled bronchodilators. Six months postexposure, 54% complained of cough and 46% complained of dyspnea on exertion. All patients had normal PFTs; 8.3% had a significant bronchodilator response. All had normal exercise tests (mean VO2max = 90 +/- 3% predicted) and chest CTs. With IOS, 80% had a significant bronchodilator response (decreased resistance > 12% and SD score > 1; mean change = 21.1 +/- 9.9%, mean SD score = 3.1 +/- 2.5). No correlation existed between changes in resistance or reactance and spirometric values. Patient symptoms correlated significantly with bronchodilator response on IOS resistance (R=0.61, p=0.03). More than 50% of patients exposed to the combustion products of a faulty ice resurfacer remained symptomatic six months after exposure. Despite persistence of symptoms, conventional pulmonary function tests and radiologic evaluation did not reveal airway abnormalities. IOS showed evidence of increased airway resistance and small-airway disease, which correlated with patient symptoms.

The utility of the forced oscillation technique in assessing bronchodilator responsiveness in patients with asthma

To address the utility of the forced oscillation technique (FOT) in assessing bronchodilator responsiveness compared with forced expiratory volume in 1s (FEV(1)). This is a retrospective analysis of consecutive 126 patients with a clinical history of asthma without any other lung diseases at a pulmonary function testing laboratory. The following measurements were obtained three times each, before and after two doses of pirbuterol 0.2mg inhalation: the respiratory resistance at 5Hz (Rrs5), the mean respiratory resistance between 5 and 20Hz (Rrs5-20), and the mean respiratory conductance (Grs5-20) by FOT and the FEV(1) by spirometer. These measurements were transformed into dimensionless subject-specific effect-size "d-scores" by dividing them by the estimated pooled within-subject standard deviation. Descriptive statistics for each value were the following [mean baseline value (+/-sd), Delta value (pre- minus post value), and d-score (P value compared to FEV(1))]: Grs5-20 (Ls(-1)kPa(-1)) [1.79+/-0.53, Delta=+0.39, d=2.64 (P<0.001)], Rrs5-20 (kPaL(-1)s) [0.60+/-0.16L, Delta=-0.10, d=2.56 (P=0.001)], Rrs5 (kPaL(-1)s) [0.78+/-0.25, Delta=-0.16, d=2.52 (P<0.001)], and FEV(1) (L) [1.90+/-0.64, Delta=-0.20, d=1.83]. The higher d-score of Grs5-20, Rrs5-20 and Rrs5 compared to FEV(1) indicates that these are better indicators for bronchodilator response than FEV(1). The percentages of subjects exhibiting change in the expected direction after bronchodilator were not significantly different between each value: Rrs5 (85.7%), Rrs5-20 (83.3%), Grs5-20 (83.3%), and FEV(1) (83.3%) [P>0.05]. Several forced oscillation measures, namely Grs5-20, Rrs5-20 and Rrs5, are more accurate and sensitive for detecting bronchodilator response than FEV(1) in patients with asthma.

The American Thoracic Society’s Spirometric Criteria Alone is Inadequate in Asthma Diagnosis

The diagnosis of asthma is based on clinical symptoms, physical examination and pulmonary function tests, and can be very challenging. Most patients with asthma have a significant postbronchodilator response on spirometry indicating airway hyperresponsiveness. However, having a significant bronchodilator response by itself is not diagnostic of asthma. The definition of a 'significant' response has also been controversial. Many respirologists use the American Thoracic Society (ATS) postbronchodilator response criteria of 12% (provided it is 200 mL or greater) improvement in forced expiratory volume in 1 s (or forced vital capacity) from the baseline spirometry. In the present study, 644 patients who met the ATS criteria for a significant postbronchodilator spirometric response were retrospectively reviewed. The staff respirologist's diagnosis of asthma, based on all clinical and pulmonary function data, was used as the standard for the diagnosis of asthma. Relying on spirometric criteria alone was inadequate in asthma diagnosis because only 54.7% of 310 patients who met the ATS bronchodilator response criteria were thought to have clinical asthma. Increasing the postbronchodilator percentage improvement from the ATS criteria only marginally improved diagnostic specificity and resulted in a decline in sensitivity. The results of the present study further emphasize the need to use spirometric criteria as a guide but not as an unimpeachable gold standard with which to make a diagnosis of asthma. The diagnosis of asthma depends on expert physician correlation of patient history, physical examination and pulmonary function test results.