Delta FEV1 Research Articles

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up

BackgroundHigh blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment.MethodsCOPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened.Results63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83–0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts].ConclusionsBlood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Surfactant Protein B Plasma Levels: Reliability as a Biomarker in COPD Patients.

The diagnosis of COPD is based on both clinical signs and functional tests. Although there are different functional tests used to assess COPD, no reliable biomarkers able to provide information on pathogenesis and severity are available. The aim of the present study is to explore the relationship between surfactant protein B (Sp-B) serum levels and clinical, radiological, and functional pulmonary parameters in COPD patients. Forty COPD patients and twenty smokers without airflow limitations or respiratory symptoms were enrolled. Each patient was given questionnaires (CAT and mMRC) and 6MWT, spirometry, DLCO, and computer tomography (CT) were performed. All participants underwent a venous blood sample drawing, and quantitative detection of their Sp-B plasma levels was performed by an enzyme-linked immunosorbent assay. The spirometry and Sp-B plasma levels were assessed after 12 months. A statistically significant difference was found in the plasma Sp-B levels between COPD patients compared to the other group (4.72 + 3.2 ng/mL vs. 1.78 + 1.5 ng/mL; p < 0.001). The change in FEV1 after 12 months (Delta FEV1) showed a significantly negative correlation with respect to the change in Sp-B levels (Delta SpB) (r = -0.4; p < 0.05). This correlation indicates that increasing the plasma dosage of SpB is a foretoken of functional decline. SpB may be considered as a useful marker in COPD assessment and provides prognostic information on lung functional decline. Despite its usefulness, further studies are needed to define its reliability as a biomarker.

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features

BackgroundSome patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression.MethodsSixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed.ResultsCompared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = − 0.323, p = 0.018; KL-6: rS = − 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001).ConclusionsSerum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

BackgroundWe have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. MethodsIn this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). ResultsAfter 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = −0.5376; P < .001 and r = −0.3285; P < .001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β = −0.57, P = .019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P = .029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665–0.947]; P < .001). ConclusionsThis study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.

262 Glucose tolerance in cystic fibrosis patients: The DIAMUCO study

Objective: CFRD is the most common comorbidity in CF. The recommended treatment of CFRD is Insulin, but other options are also in use. Only few data exist related to other treatment options. Therefore we analyzed the German CFregister for the documented therapy of CFRD. Methods: Data from the German CF-register were used from patients with CFRD in 2010 in a retrospective observational study. Delta FEV1% and delta BMI-Zscore from 2 year before diagnosis of CFRD to year of diagnosis and from year of diagnosis to 2 years after were calculated for each treatment group (Insulin, oral anti-diabetic drugs, no therapy with drugs) and compared using ANOVA-analysis. Results: 798 patients with CFRD were documented in 2010. 51.9%.were female; age (mean±SD) at diagnosis 23.8±9.3 years; CFRD duration 5.8±4.5 years. Treatment: 57.6% Insulin, 9.8% oral anti-diabetic drugs, 2.1% with both and 30.2% without any drug treatment. The mean (±SD) CFRD duration in the non-treated patients was 4.5±4.0 years. ANOVA tests showed no differences between treatment groups regarding changes in FEV1% and BMI-Z-score from 2 years before to the year of diagnosis and delta FEV1 and delta BMI-Z-score and from year of diagnosis to 2 years later. Conclusions: The percentage of patients treated with oral anti-diabetic drugs is in the international published range. We know the weakness of retrospective studies. Nevertheless the numbers are high and the observation time is long. Our data point to the question if insulin is the only successful initial treatment of CFRD in all CF patients. At least a part of patients with CFRD seems to be well treated with other regimes. Supported by German CF Foundation.

Beta2-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population

Association and linkage studies of beta₂-adrenergic receptor (beta₂AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta₂AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions -47, -20, 46, 79, and 252) of beta₂AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta₂AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV₁) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV₁ (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV₁ (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype -47 T/-20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta₂AR SNPs or beta₂AR haplotype.

Association between β‐adrenoceptor gene polymorphisms and relative response to β2‐agonists and anticholinergic drugs in Japanese asthmatic patients

Whether beta(2)-adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to beta(2)-agonist medications remains controversial, partly due to factors that may confound pharmacogenetic associations, including age, cigarette smoking and airway remodelling. To overcome these problems, we performed an analysis using parameters that reflected the specific bronchodilator response to beta(2)-agonists. The increases in FEV(1) after inhalation of procaterol hydrochloride (Delta FEV(1) procaterol) or oxitropium bromide (Delta FEV(1) oxitropium), and after sequential inhalation of procaterol and oxitropium (total airway reversibility), were measured in 81 Japanese patients with moderate to severe asthma. Approximately 3 kb of the DNA sequence of the coding and 5'-flanking regions of ADRB2 were genotyped by direct sequencing and PCR-restriction fragment length polymorphism assay. The mean age of the participants was 54 years, and 38 (47%) were smokers. Although Delta FEV(1) procaterol and Delta FEV(1) oxitropium adjusted for predicted FEV(1) were not associated with ADRB2 polymorphisms, the ratio of Delta FEV(1) procaterol to total airway reversibility was significantly associated with the ADRB2 A46G genotype (P < 0.05). Patients who were homozygous for the A46 allele (arginine at amino acid 16) were more responsive than carriers of the G46 (glycine 16) allele (P = 0.008). Multivariate linear regression analysis showed that Delta FEV(1) procaterol was correlated with the number of A46 alleles (P = 0.014), and also with total airway reversibility (P < 0.001) and smoking index in current smokers (P = 0.009). The ADRB2 A46G polymorphism was associated with a relatively greater bronchodilator responsiveness to beta(2)-agonists even in elderly asthmatic patients and smokers.

Effect of dust exposure and nitrogen oxides on lung function parameters of German coalminers: a longitudinal study applying GEE regression 1974–1998

Workplace limits for dust and nitrogen oxides are under review in Germany and the EU. We conducted a study on German coal miners to determine the effects of exposure on lung function. Longitudinal inception cohort study (1974-1998) on miners who began working underground at two coal mines between 1974 and 1979. We determined the number of shifts worked underground, the exposure to coal mine dust, quartz dust, nitrogen oxides (NO, NO(2)), smoking behavior, and three lung function parameters (FVC, FEV(1), FEV(1)/FVC). General estimation equation (GEE) models were fitted. 1,369 miners worked an average 3,017 shifts (S) underground. The mean respirable coal mine dust concentration was 1.89 mg/m(3) (quartz: 0.067 mg/m(3)), and the nitrogen oxide concentrations were 0.58 ppm (NO) and 0.007 ppm (NO(2)). On average, 9 measurements of lung function were available per miner. Compared to reference values, the findings were unexceptionable (103, 101, and 99%) on average. GEE-regression models did not reveal detrimental dust exposure effects. Nitrogen oxides (NO (x) = NO + NO(2)) showed small but clearly insignificant effects on lung function: delta FVC = -0.0008 ml/(220 ppmS), P = 0.86, delta FEV(1) = -0.003 ml/(220 ppmS), P = 0.50 and delta FEV(1)%FVC = -0.07%/(220 ppmS), P = 0.22. The effect of dust exposure on lung function described in older British and American coal miner studies was not confirmed. This can be explained partly by differences in methods (here: longitudinal studies, no prior exposure), but also by lower dust levels. NO (x) exposures showed no relevant influence on lung function-a result confirming findings from British coal mining.

Can the Use of HEPA Cleaners in Homes of Asthmatic Children and Adolescents Sensitized to Cat and Dog Allergens Decrease Bronchial Hyperresponsiveness and Allergen Contents in Solid Dust?

Background: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). Methods: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. Results: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV₁ after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. Conclusion: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study.

Spirometry in an unselected group of 6‐year‐old children: The DARC birth cohort study

This study presents reference equations for spirometric parameters in 6-year-old children and evaluates the ability of spirometry to discriminate healthy children from children with asthma. Baseline spirometry and respiratory symptoms were assessed in 404 children participating in a longitudinal birth cohort study. Children with known asthma, possible asthma and a control group also performed bronchodilator measurements. At least two acceptable flow-volume curves at baseline were obtained by 368/404 children (91%). The two best values for FEV1 and FVC were within 5% of each other in 88% and 83% of children, respectively. Linear regression analyses for 242 children included in the reference population demonstrated height to be the main predictor of all spirometric indices except FEV1/FVC. FEV1, FEV75, and FVC correlated reasonably to anthropometric data in contrast to flow parameters. Gender differences were found for FEV1, FVC, and FEV75, but not for flow parameters. Asthma was diagnosed in 25/404 children. Baseline lung function in healthy children and children with asthma overlapped, although asthmatic children could be discriminated to some extent. Bronchodilator tests showed a difference in Delta FEV1(mean) between healthy children and children with asthma (3.1% vs. 6.1%, P < 0.05). At a cut-off point of Delta FEV1 = 7.8%, bronchodilator tests had a sensitivity of 46% and a specificity of 92% for current asthma. Spirometry including bronchodilator measurements was demonstrated to be feasible in 6-year-old children and reference values were determined. Spirometry aids the diagnosis of asthma in young children, but knowledge on sensitivity and specificity of these measurements is a prerequisite.

How Can We Assess the Perception of Induced Dyspnea in Chronic Obstructive Pulmonary Disease?

To evaluate various methods for studying the perception of dyspnea in chronic obstructive pulmonary disease (COPD) using a new parameter, the change in Borg scale rating, and others already in use: the linear regression slope and the application of Stevens' law to the response perception curve--ie change in forced expiratory volume in 1 second (delta FEV1)--change in dyspnea (delta dyspnea). A bronchial challenge test was performed on 70 patients with stable COPD and no contraindications for performing the test (European Respiratory Society criteria), during which dyspnea was measured (Borg scale) after each nebulization. Perception was analyzed using: a) the linear regression slope of delta FEV1 plotted against (delta dyspnea); b) the exponent n of Stevens' law (psi=k phi n, in which psi is delta dyspnea and phi is delta FEV1, with perception being poor when n<1 and good when n>1), and c) change in Borg: difference between dyspnea when FEV1 has fallen 20% and dyspnea after saline inhalation. Subjects were classified according to the slope and change in Borg as hypoperceivers, normal perceivers, or hyperperceivers. These 2 methods of classification were compared using the kappa statistic. According to the exponent n, all patients were hypoperceivers (n<1). According to the slope, there were 33 hypoperceivers, 28 normal perceivers, and 9 hyperperceivers. The change in Borg classified 37 subjects as hypoperceivers, 23 as normal perceivers, and 10 as hyperperceivers. All except 5 subjects were classified in the same way by the slope and the change in Borg (kappa=0.88). In most of the 5 cases of discrepancy, the slope classified subjects as better perceivers. The n exponent is not valid for evaluating the perception of dyspnea induced by a bronchial challenge test in COPD. Change in Borg is at least as useful as the slope for evaluating perception of dyspnea. The percentage of patients with this disease who are hyperperceivers is high.

Change of Lung Volumes in Chronic Obstructive Pulmonary Disease Patients with Improvement of Airflow Limitation after Treatment

12.3%; lung volume changes were analyzed in 17 patients for the flow response. Results : The mean age of the subjects was 66 years; 76% were men. The mean baseline FEV1, FEV1/FVC and RV were 0.98L (44.2% predicted), 47.5% and 4.65 L (241.5%), respectively. The mean follow up duration was 80 days. The mean differences in the FEV1, FVC, TLC and RV were 0.27 L, 0.39 L, -0.69 L and -1.04 L, respectively, during the follow up periods. There was no correlation between the delta FEV1 and delta RV values(r=0.072, p=0.738). Conclusion : To appropriately evaluate the lung function in patients with moderate to severe airflow limitations; serial lung volume measurements would be helpful. (Tuberc Respir Dis 2004; 57:143-147)

Body Composition Analysis and Changes in Airways Function in Obese Adults After Hypocaloric Diet

To determine the relationship between weight-loss and pulmonary function indexes, focusing on forced expiratory flows (ie, FEV(1), forced expiratory flow at 50% of vital capacity [FEF(50)], forced expiratory flow at 75% of vital capacity, and forced expiratory flow at 25 to 75% of vital capacity [FEF(25--75)]). Specifically, to determine the effect of losses in total and segmental fat mass (FM) and of modifications in lean body mass, after restricted hypocaloric diet, on pulmonary function among obese adults. Cross-sectional, observational. Human Physiology Division, Faculty of Medicine and Surgery, "Tor Vergata" University, Rome, Italy. Thirty obese adults (mean [+/- SD] baseline body mass index [BMI], 32.25 +/- 3.99 kg/m(2)), without significant obstructive airway disease, were selected from among participants in a weight-loss program. Anthropometric, body composition (BC), and respiratory parameters of all participants were measured before and after weight loss. Total and segmental lean body and FM were obtained by dual-energy x-ray absorptiometry. Dynamic spirometric tests and maximum voluntary ventilation (MVV) were performed. The BC parameters (ie, body weight [BW], BMI, the sum skinfold thicknesses, thoracic inhalation circumference, thoracic expiration circumference, total FM, and trunk FM [FMtrunk]) were significantly decreased (p < or = .0001) after a hypocaloric diet. The mean vital capacity, FEV(1), FEF(50), FEF(25-75), expiratory reserve volume, and MVV significantly increased (p < or = 0.05) with weight loss. The correlation coefficient for Delta FEF(25--75) (r = 0.20) was numerically higher than Delta FEF(50) and Delta FEV(1) (r = 0.14 and r = 0.08, respectively) for the BW loss. Moreover, the correlation coefficient for Delta FEF(25--75) (r = 0.45) was significantly higher (p < or = 0.02) than those for Delta FEF(50) and Delta FEV(1) (r = 0.38 and r = 0.15, respectively) for FMtrunk loss. This study shows that a decrease in total and upper body fat obtained by restricted diet was not accompanied by a decrease in ventilatory muscle mass. FMtrunk loss was found to have improved airflow limitation, which can be correlated to peripheral airways function.

The effects of adiposity and weight change on forced expiratory volume decline in a longitudinal study of adults.

To investigate whether changes in anthropometric measures are related to lung function decline. A national 7-y follow up study in Great Britain. 3391 adults aged 18-73 y at baseline. The primary outcome measure was change in forced expiratory volume in one second (Delta FEV1), adjusted for age, height and sex. This was related to changes in weight, body mass index, waist circumference, hips circumference and waist to hip ratio. Changes in weight, body mass and waist circumference, adjusted for confounders including mean level, were all associated with changes in FEV1 (P<0.001), with all effects stronger in men than women (P<0.05). Change in waist to hip ratio was related in men (P=0.01), but not in women (P=0.34). A 10 kg weight increase induced an additional fall in FEV1 of 96 ml (95% confidence interval (95% CI 65-127 ml) in men, and 51 ml (95% CI. 27-75 ml) in women. In men, the effect increased with average weight and obesity and was more pronounced in middle age. This phenomenon was not present in women, possibly due to gender differences in weight distribution in later adult life. Smoking did not appear to influence the magnitude of effect in either sex. The detrimental effect of weight gain on FEV1 in subjects that stopped smoking between studies appeared small in comparison to the benefit of smoking cessation. Increases in adult body mass are predictors of FEV1 decline, especially among older and heavier men, where weight reduction may significantly slow lung function decline.

Simple forced oscillatory technique and spirometry in assessment of bronchial responsiveness in non‐asthmatic and asthmatic subjects

Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow-volume spirometry in detection of bronchial changes during induced bronchoconstriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non-asthmatic subjects (n = 61) of which 44 were classified as responders (delta FEV1 > or = 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (delta max/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose-response curves were similar for all parameters. In the non-asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60-Rrsfo versus PC10-FEV1, P < 0.05; PC60-Rrsfo versus PC25-MMEF, P < 0.01). In the non-asthmatic responsive subjects, the correlations between PC60-Rrsfo and PC25-MMEF were significant (P < 0.05). Thus, Rrsfo at a fixed 8 Hz frequency and built-in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non-asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.

Hospitalization trends for paediatric asthma in eastern Finland: a 10-yr survey

Although persistent activation of the inspiratory muscles and narrowing of the glottic aperture during expiration have been indicated as relevant mechanisms leading to dynamic hyperinflation in acute asthma, expiratory flow limitation (EFL) has recently been proposed as a possible triggering factor for increasing endexpiratory lung volume (EELV). To establish whether the attainment of maximal flow rate during tidal expiration could elicit dynamic elevation of EELV, breathing pattern, change in EELV by measuring inspiratory capacity (IC) and occurrence of EFL by the negative expiratory pressure (NEP) method were monitored in 10 stable asthmatic subjects during methacholine-induced, progressive bronchoconstriction in seated position. Change in dyspnoea was scored using the Borg scale. At maximum response forced expiratory volume in one second (FEV1) fell on average by 45+/-2% (p&lt;0.001 versus control), while IC decreased 29+/-2%, (by 0.89+/-0.07 L, (p&lt;0.01 versus control)). Only 2 subjects exhibited EFL at the end of methacholine challenge. In 7 subjects EELV started to increase before the occurrence of EFL. Dyspnoea, which increased from 0.2+/-0.1 to 5.5+/-1.0 (Borg scale) at maximum response (p&lt;0.001), was significantly related to the level of bronchoconstriction as assessed by change in (delta)FEV1 (r=0.72; p&lt;0.001) and to dynamic hyperinflation as measured by deltaIC (r=0.50; p&lt;0.001). However, for both deltaFEV1 and deltaIC the slope of the relationship with increasing dyspnoea was highly variable among the subjects. It is concluded that in acute methacholine-induced bronchoconstriction, dynamic hyperinflation may occur in the absence of expiratory flow limitation and that expiratory flow limitation does not represent the triggering factor to generate dynamic hyperinflation. In these circumstances, dyspnoea appears to be related to the increase in end-expiratory lung volume and not to the onset of expiratory flow limitation.

Dynamic hyperinflation and flow limitation during methacholine-induced bronchoconstriction in asthma.

Although persistent activation of the inspiratory muscles and narrowing of the glottic aperture during expiration have been indicated as relevant mechanisms leading to dynamic hyperinflation in acute asthma, expiratory flow limitation (EFL) has recently been proposed as a possible triggering factor for increasing endexpiratory lung volume (EELV). To establish whether the attainment of maximal flow rate during tidal expiration could elicit dynamic elevation of EELV, breathing pattern, change in EELV by measuring inspiratory capacity (IC) and occurrence of EFL by the negative expiratory pressure (NEP) method were monitored in 10 stable asthmatic subjects during methacholine-induced, progressive bronchoconstriction in seated position. Change in dyspnoea was scored using the Borg scale. At maximum response forced expiratory volume in one second (FEV1) fell on average by 45+/-2% (p<0.001 versus control), while IC decreased 29+/-2%, (by 0.89+/-0.07 L, (p<0.01 versus control)). Only 2 subjects exhibited EFL at the end of methacholine challenge. In 7 subjects EELV started to increase before the occurrence of EFL. Dyspnoea, which increased from 0.2+/-0.1 to 5.5+/-1.0 (Borg scale) at maximum response (p<0.001), was significantly related to the level of bronchoconstriction as assessed by change in (delta)FEV1 (r=0.72; p<0.001) and to dynamic hyperinflation as measured by deltaIC (r=0.50; p<0.001). However, for both deltaFEV1 and deltaIC the slope of the relationship with increasing dyspnoea was highly variable among the subjects. It is concluded that in acute methacholine-induced bronchoconstriction, dynamic hyperinflation may occur in the absence of expiratory flow limitation and that expiratory flow limitation does not represent the triggering factor to generate dynamic hyperinflation. In these circumstances, dyspnoea appears to be related to the increase in end-expiratory lung volume and not to the onset of expiratory flow limitation.

Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ).

Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development. Highly variable rates of decline in lung function are reported in PiZZ individuals. The annual decline in forced expiratory volume in one second (FEV1; delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult PiZZ individuals included in the Swedish national AAT deficiency register. Delta FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current smokers after performing at least two spirometries during a follow-up time of 1 yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never-smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41 mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI 58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found between cigarette consumption and delta FEV1 in current smokers and exsmokers. In never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No sex differences were found in delta FEV1. In conclusion, among PiZZ individuals, the change in forced expiratory volume in one second is essentially the same in never-smokers and exsmokers. Smoking is associated with a dose-dependent increase in the change in forced expiratory volume in one second.

The Current Dilemma with Spirometric Inclusion Criteria for Asthma Drug Trials

Spirometric inclusion criteria for asthma drug studies often require resting airflow obstruction and resting bronchoconstriction. By current standards, these criteria define suboptimal to poor asthma control. To determine what proportion of asthmatic patients attending a tertiary University-based respiratory clinic meet typical drug study spirometric criteria of a baseline FEV1 of 50% to 80% predicted and > or = 15% delta FEV1 improvement following 200 micrograms inhaled albuterol. A retrospective review was performed on charts of white caucasian asthmatic patients attending three respiratory physician outpatient clinics at a University-based tertiary referral center. We reviewed charts of all patients with chronic asthma under current therapy. We excluded subjects with additional lung diseases that might affect lung function. Spirometric data were extracted from the most recent scheduled outpatient visit. We reviewed 590 charts of patients with mean age 35.3 +/- 18.3 years (range 6 to 94), 43% male, and 50% atopic. There was objective evidence of variable airflow obstruction or airway hyperresponsiveness in 70.2%; the diagnosis of asthma was based on historical data alone in 29.8%. The majority of patients (87.5%) required inhaled corticosteroids with more than 50% using medium to high doses. Baseline FEV1 was > 80% in 84.6% of subjects, 50% to 80% in 14.4%, and < 50% in 1.0%. FEV1 improved by > or = 15% 10 to 15 minutes after 200 micrograms inhaled albuterol in 13.6%. Only 9.0% of the 590 asthmatic patients fulfilled both criteria (FEV1 50% to 80% and delta FEV1 > or = 15%). Less than 10% of asthmatic patients attending a tertiary referral respiratory clinic fulfilled typical spirometry inclusion criteria for asthma drug trials. We suggest this approach to enrollment in asthma drug studies be reevaluated.

Methacholine dose-response slopes from maximal bronchial challenge tests in asthmatic children: methodological aspects.

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholine (dose range: 0.097-30.08 mumol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a delta FEV1 > or = 20%; and (2) a MFEV1 > or = 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % delta FEV1 x mumol-1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student's t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 +/- 2.7 delta FEV1%. mumol-1) was 2.88 times higher than DRR50% (31.6 +/- 3.4 delta FEV1%. mumol-1), and the LSS20% (89.1 +/- 2.8% delta FEV1. mumol-1) was 3.10 times higher than LSS50% (28.8 +/- 1.5% delta FEV1. mumol-1). The goodness of fit of LSS50% was significant in all cases, whereas LSS20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.