Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: The PLATINO study

BackgroundAcute bronchodilator responsiveness is an area of discussion in COPD. No information exists regarding this aspect of the disease from an unselected COPD population. We assessed acute bronchodilator responsiveness and factors influencing it in subjects with and without airway obstruction in an epidemiologic sample.MethodsCOPD was defined by GOLD criteria (post-bronchodilator FEV₁/FVC < 0.70). In this analysis, subjects with pre-bronchodilator FEV₁/FVC <0.70 but ≥0.70 post-bronchodilator were considered to have reversible obstruction. Bronchodilator responsiveness after albuterol 200 μg was assessed using three definitions: a) FVC and/or FEV₁ increment ≥12% plus ≥200 mL over baseline; b) FEV₁ ≥ 15% increase over baseline; and c) FEV₁ increase ≥10% of predicted value.ResultsThere were 756 healthy respiratory subjects, 481 subjects with reversible obstruction and 759 COPD subjects. Depending on the criterion used the proportion of person with acute bronchodilator responsiveness ranged between 15.0–28.2% in COPD, 11.4–21.6% in reversible obstructed and 2.7–7.2% in respiratory healthy. FEV₁ changes were lower (110.6 ± 7.40 vs. 164.7 ± 11.8 mL) and FVC higher (146.5 ± 14.2 mL vs. ?131.0 ± 19.6 mL) in COPD subjects compared with reversible obstructed. Substantial overlap in FEV₁ and FVC changes was observed among the groups. Acute bronchodilator responsiveness in COPD persons was associated with less obstruction and never smoking.ConclusionsOver two-thirds of persons with COPD did not demonstrate acute bronchodilator responsiveness. The overall response was small and less than that considered as significant by ATS criteria. The overlap in FEV₁ and FVC changes after bronchodilator among the groups makes it difficult to determine a threshold for separating them.     

Acute Bronchodilator Response Has Limited Value in Differentiating Bronchial Asthma from COPD

Background. Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV₁ and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology. Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results. None of the expressions of response gave a clear-cut separation between the two diseases. A ΔFEV₁≥ 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (ΔFEV₁%predicted ≥ 9% and ΔFEV₁ of ≥ than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions. It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD.     

Prevalence and features of asthma–chronic obstructive pulmonary disease overlap in Northern Italy general population

Objective: There is controversy about the diagnostic criteria, prevalence, symptoms, and spirometry characteristics of asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO). Recent data indicate that the fixed method for diagnosing airway obstruction (AO) may overestimate ACO prevalence in the elderly, and a variable method may be more accurate. We aimed at estimating ACO prevalence in a general population sample and comparing patient and clinical features in subjects with ACO, COPD, and asthma. Methods: We analyzed data from a cross-sectional study estimating COPD prevalence in randomly selected adults aged 20–79 years in Verona, Italy, and estimated prevalence and analyzed characteristics of asthma, COPD, and ACO. ACO was defined as AO (Forced Expiratory Volume in one second–FEV₁/ Forced Vital Capacity–FVC < Lower Limit of Normal–LLN), highly positive bronchodilator test (≥15% increase in FEV₁ and FVC ≥400 mL), and personal self-reported history of physician diagnosed asthma and atopy. Results: One thousand two hundred and thirty-six patients were included; 207 (16.7%) had asthma, COPD, or ACO (mean ages: 61.2, 59.7, and 57.2 years, respectively). The 3 groups had similar clinical and demographic variables; however, spirometry revealed differences between ACO and COPD patients, particularly post-bronchodilator FEV₁ reversibility, which was detected in ACO and asthma patients but not in those with COPD. Conclusion: ACO prevalence in Northern Italy was estimated at 2.1%, in the range of values reported by previous studies. Marked differences between ACO and COPD revealed by spirometry may have important clinical implications in terms of treatment for patients with ACO.     

Significant Bronchodilator Responsiveness and “Reversibility” in a Population Sample

ABSTRACT

Chronic 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.     

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

Background

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

Methods

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

Results

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

Conclusions

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

Use of specific airway resistance to assess bronchodilator response in children

Background and objective: Changes in specific airway resistance (ΔsRaw) after bronchodilation, as measured by plethysmography and FEV₁, are frequently considered to be interchangeable indices of airway obstruction. However, the baseline relationship between these two indices is weak, and the value of ΔsRaw that best predicts FEV₁ reversibility in children has yet to be determined. The aim of this study was (i) to establish the sRaw cut‐off value that best distinguishes between positive and negative bronchodilator responses, as measured by FEV₁ reversibility; (ii) to determine whether the discrepancy between ΔsRaw and ΔFEV₁ might be explained by independent correlations between ΔFEV₁ and both ΔsRaw (mainly airway obstruction) and ΔFVC (airway closure); and (iii) to assess the effect of height and age on the relationship between ΔsRaw and ΔFEV₁. Methods: A retrospective study was performed in 481 children (median age 10.5 years, range 6.1–17.6) with actual or suspected asthma, for whom sRaw and spirometry data were obtained at baseline and after administration of a bronchodilator. Results: The sRaw cut‐off value that best predicted FEV₁ reversibility was a 42% decrease from baseline (P = 0.0001, area under the curve 0.70, sensitivity 55%, specificity 77%) and was independent of height and age. Changes in FEV₁ were significantly but independently related to ΔsRaw and ΔFVC (index of air trapping) (r = 0.40, P < 0.0001 and r = 0.39, P < 0.0001, respectively). Conclusions: A 42% decrease in sRaw predicted FEV₁ reversibility reasonably well, whereas a smaller decrease in sRaw failed to detect approximately one out of two positive responses detected by FEV₁, with no influence of height or age.     

Relationship between polymorphisms in the 5' leader cistron, positions 16 and 27 of the adrenergic β2 receptor gene and asthma in a Han population from southwest China

Background and objective: Adrenergic β2 receptors (ADRB2) play an important role in regulating pulmonary function. Many previous studies have investigated possible associations between polymorphisms in the ADRB2 gene and asthma, but have yielded conflicting results. Furthermore, little is known regarding the possible role of the Arg19Cys polymorphism in susceptibility to asthma among Chinese. Methods: This case–control association study involved 238 patients with asthma and 265 healthy subjects from a Han population in southwest China. For all subjects, the 5′ leader cistron Arg19Cys, Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene were characterized by direct sequencing. Genotype, allele and haplotype frequencies were determined. In addition, to evaluate the association between the ADRB2 polymorphisms and lung function, bronchodilator response to inhaled β2 agonists (400 µg of albuterol) was assessed in the asthmatic patients. Results: There were no significant differences in genotype or allele frequencies for the three ADRB2 polymorphisms between the two cohorts. The Arg19/Arg16/Gln27 haplotype was more frequent among asthmatic patients than control subjects (odds ratio 2.24, 95% confidence interval (CI): 1.05–4.73, P = 0.04). Moreover, the Arg19/Cys19 genotype was associated with a lower FEV₁% (mean difference ?4.5, 95% CI: ?12.5 to 3.6, P = 0.02) and FEV₁/FVC (mean difference 8.9, 95% CI: 8.5–9.4, P = 0.01). The bronchodilator response to albuterol was also marginally lower in individuals who were homozygous for the Arg19 genotype (mean difference 4.2, 95% CI: 3.7–4.8, P = 0.03). Conclusions: The Arg19/Cys19 genotype was an independent risk factor for lower FEV₁% and FEV₁/FVC. Asthmatic patients with the Arg19/Arg19 genotype showed decreased responsiveness to albuterol. Furthermore, the Arg19/Arg16/Gln27 haplotype may contribute to increased susceptibility to asthma in the Chinese population.     

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

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

Gender Differences in Asthma Management and Quality of Life

Background. Objective assessment of airway function is important in epidemiologic studies of asthma to facilitate comparison between studies. Airway hyperresponsiveness (AHR), peak expiratory flow (PEF) variability, and bronchodilator reversibility (BR) are widely used as markers of airway lability in such studies. Data from a survey of a population sample of adolescents and young adults (n = 609; 288 males), aged 13–23 years, were analyzed to investigate whether AHR, PEF variability, and BR can be used interchangeably as markers of asthma in an epidemiological setting. Methods. Case history, including self-reported and doctor-diagnosed asthma, smoking habits, and use of asthma medication, was obtained by interview and questionnaire. Lung function, airway responsiveness (positive test: PC₂₀ FEV₁< 16 mg/mL histamine), PEF variability (positive test: amplitude percentage mean > 20%), BR (positive test: ΔFEV₁ [(FEV₁max ? FEV₁min)/FEV₁max) 100]> 10%), blood eosinophil count, and skin prick test reactivity were measured by using standard techniques. Results. The prevalence of a positive test was AHR 16.4%, PEFpos 13.3%, and BRpos 7.2%, respectively; 73.5% of the sample had three negative tests. Among the 74 participants with current self-reported asthma (12.2%), 34 subjects (46%) had more than one positive test. Using AHR as the only objective marker of asthma identified 93% of the participants with current asthma, whereas PEF and BR identified 45% and 10%, respectively. Confining the analysis to participants with only one positive test revealed that 61% of the subjects with isolated AHR had current asthma, whereas none of the subjects with isolated BRpos had asthma, and only one participant with isolated PEFpos had current asthma. Degree of histamine responsiveness was closer associated with other asthma-related factors, including self-reported asthma, use of asthma medication, and level of lung function, than PEF variability and bronchodilator responsiveness. Conclusions. Airway responsiveness to histamine, diurnal peak-flow variability, and bronchodilator reversibility cannot be used interchangeably as objective markers of asthma in epidemiologic studies. On the basis of the present findings, airway hyperresponsiveness to a nonspecific bronchoconstrictor is recommended as the objective marker of asthma-related airway lability.     

Baseline and post-bronchodilator interrupter resistance and spirometry in asthmatic children

In children unable to perform reliable spirometry, the interrupter resistance (R_int) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use R_int as a surrogate for spirometry. We aimed at comparing R_int and spirometry at baseline and after bronchodilator administration in a large population of asthmatic children. We collected retrospectively R_int and spirometry results measured in 695 children [median age 7.8 (range 4.8–13.9) years] referred to our lab for routine assessment of asthma disease. Correlations between R_int and spirometry were studied using data expressed as z‐scores. Receiver operator characteristic curves for the baseline R_int value (z‐score) and the bronchodilator effect (percentage predicted value and z‐score) were generated to assess diagnostic performance. At baseline, the relationship between raw values of R_int and FEV₁ was not linear. Despite a highly significant inverse correlation between R_int and all of the spirometry indices (FEV₁, FVC, FEV₁/FVC, FEF_25–75%; P < 0.0001), R_int could detect baseline obstruction (FEV₁ z‐score ≤ ?2) with only 42% sensitivity and 95% specificity. Post‐bronchodilator changes in R_int and FEV₁ were inversely correlated (rhô = ?0.50, P < 0.0001), and R_int (≥35% predicted value decrease) detected FEV₁ reversibility (>12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R_int measurements fitted a one‐compartment model that explained the relationship between flows and airway resistance. We found that R_int had poor sensitivity to detect baseline obstruction, but fairly good sensitivity and specificity to detect reversibility. However, in order to implement asthma guidelines for children unable to produce reliable spirometry, bronchodilator response measured by R_int should be systematically studied and further assessed in conjunction with clinical outcomes. Pediatr Pulmonol. 2012. 47:987–993. © 2012 Wiley Periodicals, Inc.     

Effect of Obesity on Asthma Phenotype is Dependent upon Asthma Severity

Background. We recently reported that obese and non-obese patients with asthma have similar airflow limitation and bronchodilator responsiveness, but obese patients have more symptoms overall. There is limited information on the effect of obesity on asthmatics of varying severity measured by objective physiological parameters. Understanding how obesity affects asthmatics of differing severity can provide insights into the pathogenesis of asthma in the obese and a rationale for the therapeutic approach to such patients. Methods. Participants with asthma from two American Lung Association—Asthma Clinical Research Center (ALA-ACRC) studies were grouped by tertiles of airflow obstruction (forced expiratory volume in one second (FEV₁%) predicted, FEV₁/forced vital capacity (FVC)) and methacholine reactivity (PC₂₀FEV₁). Within each tertile, we examined the independent effect of body mass index (BMI), divided into normal weight, overweight, and obese categories, on lung function, airway reactivity, and symptoms. Results. Overall, both FEV₁ and FVC decreased and symptoms worsened with increasing BMI; airway reactivity was unchanged. When stratified by the degree of airflow obstruction, higher BMI was not associated with greater airway reactivity to methacholine. Higher BMI was associated with more asthma symptoms only in the least obstructed FEV₁/FVC tertile. When stratified by degree of airway reactivity, BMI was inversely associated with FVC in all PC₂₀FEV₁ tertiles. BMI was directly associated with asthma symptoms only in those with the least airway reactivity. Conclusions. Obesity does not influence airway reactivity in patients with asthma and it is associated with more symptoms only in those with less severe disease.     

Association of beta2-adrenoreceptor genotypes with bronchodilatory effect of tiotropium in COPD

Background and objective: Recently, there has been interest in interactions of β₂ adrenergic receptors (β₂‐AR) and muscarinic acetylcholine receptors (mAChR), which share intracellular signal transduction systems. The aim of the present study was to investigate whether bronchodilator response to tiotropium is influenced by β₂‐AR genotype in patients with COPD who show poor responsiveness to inhaled β₂‐agonists. Methods: After a 4‐week run‐in period, patients with COPD were treated with inhaled tiotropium bromide (18 μg once daily) for 8 weeks. Spirometric measurements and reversibility testing with inhaled β₂‐AR agonists were performed and health‐related quality of life was assessed using the St George's respiratory questionnaire (SGRQ) before and after treatment. Genomic DNA was prepared from peripheral blood and individual genotypes at amino acid 16 of the β₂‐AR were examined. Results: Forty‐four patients with COPD completed the study. COPD patients with the Arg/Arg genotype (n = 22) had a significant increase in FEV₁ during treatment compared with those without the Arg/Arg genotype (n = 22) (FEV₁, P = 0.009; FEV₁%, P = 0.006). While all component and total scores on the SGRQ improved significantly in both genetic groups, changes in impact and total scores were significantly greater in patients with Arg/Arg compared with those without (total scores, P = 0.005; impact scores, P < 0.001). Conclusions: These findings indicate that the homozygous Arg/Arg genotype at amino acid 16 of the β₂‐AR could affect bronchodilator response to tiotropium in patients with COPD with significant effects on health‐related quality of life.     

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

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

Determinants of Bronchodilator Responsiveness in Patients with Controlled Asthma

Short-term bronchodilator responsiveness to an inhaled β 2 adrenergic agonist was assessed by changes in forced expiratory volume in 1 second (FEV₁) in nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate disease, 20 patients; severe disease, 18 patients). Responsiveness correlated significantly with age and with percent of predicted FEV₁ (%FEV₁) except in patients with severe asthma, who showed significantly less responsiveness than others. Thus, responsiveness is closely associated with degree of airflow limitation in patients with controlled asthma and is significantly influenced by severity of disease and by aging.     

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

Background and objective: Whether β₂‐adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to β₂‐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 β₂‐agonists. Methods: The increases in FEV₁ after inhalation of procaterol hydrochloride (ΔFEV₁ procaterol) or oxitropium bromide (ΔFEV₁ 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. Results: The mean age of the participants was 54 years, and 38 (47%) were smokers. Although ΔFEV₁ procaterol and ΔFEV₁ oxitropium adjusted for predicted FEV₁ were not associated with ADRB2 polymorphisms, the ratio of ΔFEV₁ 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 ΔFEV₁ 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). Conclusions: The ADRB2 A46G polymorphism was associated with a relatively greater bronchodilator responsiveness to β₂‐agonists even in elderly asthmatic patients and smokers.     

Effect of ADRB2 (adrenergic receptor β2) gene polymorphisms on the occurrence of asthma and on the response to nebulized salbutamol in South Indian patients with bronchial asthma

Introduction: Genetic mutations in the β₂ receptor could alter its functioning and the response to β₂ agonists. The study was done to find out the effect of two commonly occurring polymorphisms-Arg16Gly and Gln27Glu, on cause of asthma and on response to nebulized salbutamol in South Indian subjects of asthma. Methods: After baseline measurements of Forced Expiratory Volume in 1st second (FEV₁), Forced Vital Capacity (FVC) and Peak Expiratory Flow Rate (PEFR), five mg of nebulized salbutamol was administered and spirometry was repeated. The increase in these parameters was calculated and patients were included for genotyping if the percentage increase in FEV₁ was ≥12%. The frequencies of these polymorphisms in patients were compared with those of healthy volunteers. Results: 112 patients and 127 healthy volunteers were genotyped. The frequencies of the polymorphisms were found to be similar to previously published Dravidian population frequencies. The frequencies of genotypes in asthmatics were similar to healthy volunteers. The increase in FEV₁, FVC and PEFR was similar across various genotypes and haplotypes in both the polymorphisms. The GG-CG haplotype was associated with 3.1 times increased occurrence of asthma (p value?=?0.02). The G allele of the Arg16Gly polymorphism was associated with lower baseline FEV₁, FVC and PEFR values, but these were not statistically significant. Conclusion: The Arg16Gly and Gln27Glu polymorphisms do not determine the occurrence of asthma individually, but the GG-CG haplotype is associated with an increased risk of asthma. There is no effect of the genotypes on the response to nebulized salbutamol.     

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

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

Comparison of Oral and Depot Intra‐muscular Steroids in Assessing Steroid‐Responsiveness in COPD

Non‐compliance or euphoria may limit the usefulness of prednisolone tablets in assessing steroid‐responsiveness in chronic obstructive pulmonary disease (COPD). Depot intra‐muscular methyl‐prednisolone (imMP), producing a plateau steroid effect over two weeks, may be more reliable. Following two weeks of placebo, twenty‐seven COPD patients (mean FEV₁ 43% predicted) participated in a two‐week randomised, double‐blind, placebo‐controlled, parallel‐design trial taking either 120 mg imMP with placebo tablets or placebo injection with prednisolone 30 mg daily. After each period, post‐bronchodilator FEV₁, forced vital capacity (FVC), inspiratory capacity (IC) and six‐minute walking distance (6MWD) were assessed and patients completed both quality‐of‐life scores (St. George's 30 and Short Form 36) and mood scores (Hospital Anxiety and Depression scores and Altman's Self‐rating Mania Scale). There were no significant changes in 6MWD, quality of life or mood scores after either type of steroids and no change in lung function after imMP. By contrast, there were small mean improvements in lung function on oral prednisolone (mean FEV₁, FVC and IC increased by 100, 320 and 150 ml, respectively). Only the improvement in FVC was significantly greater after prednisolone compared with imMP. Single depot intra‐muscular injections of steroids have no advantage over oral daily prednisolone in testing steroid‐responsiveness in COPD patients.