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.     

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017

IntroductionWe aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints.MethodsWe compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV₁/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV₁/FVC below the lower limit of normal (LLN).ResultsCOPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%–23.2%) in 1997 to 8.8% (95% CI 8.2%–9.5%) in 2017, a 59.2% decline (p < 0.001).In 2007, the prevalence was 7.7% (95% CI 6.8%–8.7%) with an upward trend of 1.1 percentage points in 2017 (p = 0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p < 0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p < 0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p = 0.95), higher in younger ages (40–49 yrs and 50–59 yrs) and also higher in women than in men in all three studies (p < 0.05).ConclusionsWe report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40–69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations.     

Tiotropium induced bronchodilation and protection from dynamic hyperinflation is independent of extent of emphysema in COPD

BackgroundThe magnitude of tiotropium (1) induced bronchodilation and (2) protection against dynamic hyperinflation in COPD phenotypes has not been studied.MethodsWe studied moderate to severe COPD patients with varying extent of emphysema as evaluated by high-resolution thin-section lung CT. Spirometry including inspiratory capacity (IC) was measured before and immediately after metronome paced hyperventilation (MPH) at 2 times resting respiratory rate for 20 s to induce dynamic hyperinflation. Spirometry was obtained at baseline and pre- and 1.5 h post-18 μg tiotropium via HandiHaler after 30 day tiotropium treatment period in a single blind, open label intervention.ResultsIn 29 COPD patients (15 M), age 70 ± 9 years (mean ± SD) with smoking history of 53 ± 37 pack years, baseline forced expiratory volume in 1 s (FEV₁) post-180 μg albuterol MDI was 1.6 ± 0.4 L (61 ± 8% predicted) and FEV₁/FVC 59 ± 6%. Lung CT emphysema score (LCTES) was 23 ± 20 (mean ± SD) on a scale of 0–100 (none to most severe emphysema). After 30-day tiotropium, FEV₁ increased 101 ± 124 mL (mean ± SD) (p < 0.001) and Spearman correlation (r) = ?0.04, p = 0.8 with LCTES; IC increased 163 ± 232 mL (p < 0.001), and r = ?0.2, p = 0.3 with LCTES. Results following MPH induced DH before and after 30-day tiotropium were significant (p < 0.001) and similar: IC decreased 340 ± 280 mL before and 337 ± 270 mL after tiotropium, and r = ?0.3, p = 0.9 with LCTES.ConclusionTiotropium significantly increased FEV₁ (L) and inspiratory capacity in moderate-severe COPD, independent of extent of lung CT emphysema score. Despite bronchodilation and lower resting lung volume, tiotropium did not abbreviate induced dynamic hyperinflation, which was also independent of underlying emphysema.     

Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist,in COPD patients

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 μg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV₁] ≥ 30% and <80% predicted and FEV₁/forced vital capacity [FVC] < 0.7, 30 min after inhalation of 80 μg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 μg (n = 92), NVA237 200 μg (n = 98) or placebo (n = 91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV₁ was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 μg the differences were 131 and 161 mL on Days 1 and 28, respectively (p < 0.05), and for NVA237 200 μg the differences were 146 and 151 mL on Days 1 and 28, respectively (p < 0.05). Peak FEV₁, FEV₁ at all timepoints up to 24 h after dosing, and FEV₁ area under the curve during 5 min–5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 μg in patients with moderate-to-severe COPD.     

Lung Hyperinflation and Its Reversibility in Patients with Airway Obstruction of Varying Severity

ABSTRACT

The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV₁/FVC <0.70. We examined relationships between indices of airway obstruction and lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV₁ decreased, while VC and IC decreased linearly. Regardless of baseline FEV₁, the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.     

Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: A multicenter,randomized study

BackgroundChronic obstructive pulmonary disease (COPD) is a growing public health problem that has increased in recent years. It similarly affects men and women, especially those who smoke. The goals of COPD pharmacotherapy are to improve lung function, reduce symptoms, prevent exacerbations, and improve patients' health status. Bronchodilators are the foundation of treatment for COPD, and the long-acting β₂-agonists formoterol and salmeterol are both indicated for regular use by patients with stable COPD.ObjectiveA clinical study was conducted to compare the onset of bronchodilator effects following treatment with formoterol 12 μg administered twice-daily (BID) or salmeterol 50 μg BID. The trial also assessed whether the bronchodilator effects of treatment resulted in significant differences in clinical response.MethodsThis was a randomized, multicenter, open-label, parallel-group study of formoterol 12 μg BID versus salmeterol 50 μg BID, both administered for 28 days. Patients were current or previous smokers aged ≥40 years, with a diagnosis of stable COPD. The primary efficacy variable was change from baseline in forced expiratory volume in 1 s (FEV₁) 5 min after drug administration on day 28. Secondary efficacy variables included changes from baseline in the 6-min walk test (6MWT) and rescue medication use. The primary variable was assessed by analysis of covariance, with baseline FEV₁ as the covariate.ResultsA total of 270 patients were randomized to formoterol 12 μg BID (n = 137) or salmeterol 50 μg BID (n = 133). In the intent-to-treat population the least square (LS) mean change from baseline in FEV₁ at 5 min postdose on day 28 was 0.13 L in the formoterol group compared with 0.07 L in the salmeterol group (P = 0.022). At 30 min postdose on day 28, the LS mean change from baseline in FEV₁ was 0.17 L in the formoterol group compared with 0.07 L in the salmeterol group (P < 0.001). Similar changes were reported at 60 min postdose (0.19 L for the formoterol group versus 0.13 L for the salmeterol group, P = 0.069). Patients in the formoterol group walked longer distances in the 6MWT and used less rescue medication compared with patients in the salmeterol group, although the differences were not statistically significant.ConclusionsSignificantly greater improvements from baseline in FEV₁ were observed at 5 and 30 min postdose with formoterol 12 μg compared with salmeterol 50 μg after 28 days of treatment. Numeric improvements in the 6MWT and rescue medication use were also observed with formoterol.     

Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design

BackgroundThe drug development process can be streamlined by combining the traditionally separate stages of dose-finding (Phase IIb) and confirmation of efficacy and safety (Phase III) using an adaptive seamless design. This approach was used in a clinical study of indacaterol, a novel once-daily (od) inhaled long-acting β₂-adrenoreceptor agonist bronchodilator for the treatment of COPD (chronic obstructive pulmonary disease).MethodsThe study comprised a dose-finding stage with dose selection after 14 days of treatment, and a second stage evaluating efficacy and safety during 26 weeks of treatment. The dose-finding stage included seven randomized treatment arms: double-blind indacaterol 75 μg, 150 μg, 300 μg or 600 μg od, the β₂-adrenoceptor agonist formoterol 12 μg twice-daily or placebo, or the anticholinergic tiotropium 18 μg od open-label. An independent data monitoring committee selected two indacaterol doses based on unblinded results of an interim analysis performed by an independent statistician. The sponsor, investigators and patients remained blinded to the results. The indacaterol doses were selected using pre-set efficacy criteria for trough (24-h post-dose) and early (1–4 h post-dose) bronchodilator effect after 14 days, and all safety data. To qualify for selection, the doses had to exceed a threshold for clinical relevance or be superior to either tiotropium or formoterol, whichever was the highest value. Selected doses were continued into the second, 26-week stage. The two other indacaterol doses not selected, and formoterol, were discontinued following dose selection.Results801 patients with moderate-to-severe COPD were evaluated. Indacaterol 150 μg was the lowest effective dose, exceeding criteria for trough FEV₁ (reference value 140 mL vs placebo) and FEV₁ AUC_1–4h (reference value 220 mL vs placebo). No safety signal was observed with any dose of indacaterol. Thus, indacaterol 150 and 300 μg were selected to continue into the second, 26-week stage.ConclusionThe adaptive seamless design is a novel and efficient way to combine dose selection with efficacy evaluation and safety confirmation in a single trial.     

Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department

RationaleTreatment of severe asthma may be difficult despite the use of several medications including parenteral corticosteroids. Intravenous magnesium sulfate (MgSO₄) is one ancillary drug for severe crisis; its inhaled use is controversial.ObjectivesTo evaluate the usefulness of inhaled MgSO₄ compared to placebo in improving lung function, oxygen saturation, and reducing hospital admission as an adjunct to standard treatment in severe asthma crisis.Patients and methodsWe conducted a placebo-controlled, double-blind clinical trial with asthmatic patients >18 years of age with asthmatic crisis and FEV₁ < 60% of predicted (%p). All subjects received 125 mg of IV methylprednisolone followed by nebulization with the combination of albuterol (7.5 mg) and ipratropium bromide (1.5 mg) diluted in 3 ml of isotonic saline solution (as placebo) or 3 ml (333 mg) of MgSO₄. After 90 min, subjects with FEV₁ < 60%p or SpO₂ < 88% or persistent symptoms were admitted to the emergency department (ED).ResultsWe included 30 patients per group who were similar at baseline. The MgSO₄ group showed higher post-bronchodilator (post-BD) FEV₁%p (69 ± 13 vs. 61 ± 12, p < 0.014) and SpO₂ (92 ± 4 vs. 88 ± 5%, p < 0.006) than the placebo group. Fewer treated patients were admitted to the ED (5 vs. 13) (p < 0.047), with relative risk (RR) of 0.26 (95% CI 0.079–0.870).ConclusionsAdding inhaled MgSO₄ treatment to standard therapy in severe asthma crisis improves FEV₁%p and SpO₂ post-BD and reduces the rate of ED admissions.     

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)     

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study

BackgroundTo assess the impact of diabetes on restrictive and obstructive lung function impairment.MethodsThis 5-year prospective study included 7524 participants aged 40–69 years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl), HbA1c ≥ 6.5% (48 mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) < 80% predicted and forced expiratory volume in 1 s (FEV₁) to FVC ratio (FEV₁/FVC) < 0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014.ResultsDuring the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04–2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72–1.21)].ConclusionDiabetes was associated with restrictive lung function impairment but not obstructive lung function impairment.     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10⁻³).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Utility of bronchodilator response for asthma diagnosis in Latino preschoolers

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

Chronic obstructive pulmonary disease diagnosis: The simpler the better? Not always

The acronym chronic obstructive pulmonary disease (COPD) has been introduced in the early 1960s to describe a disease characterized by largely irreversible airflow obstruction, due to a combination of airway disease and pulmonary emphysema, without defining their respective contribution to the pathology. COPD is a disorder that causes considerable morbidity and mortality. Currently, it represents the fourth leading cause of death in the world, and it is expected to increase both in prevalence and in mortality over the next decades. The most widely adopted definition of COPD is that of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), that recommends the use of the post-bronchodilator forced expiratory volume in the first second to forced vital capacity ratio (FEV₁/FVC) < 0.7 to define irreversible airflow obstruction. This approach, called “fixed ratio”, has been introduced to provide a simple tool for COPD diagnosis, as it is easy to remember. Even if modern medicine and research seem to prefer rigid cut-offs and classifications, this often contrasts with the complex nature of the disease. The aim of the present review is to explain that such a fixed cut-off failed to increase COPD diagnosis, and furthermore often leads to inescapable misclassification of patients, with the risk of an excessive simplification of a clinical approach necessarily complex.     

Prevalence and Determinants of COPD in Spain: EPISCAN II

BackgroundTwo previous national epidemiological studies, IBERPOC in 1997 and EPISCAN in 2007, determined the COPD burden in Spain. Changes in demographics and exposure to risk factors demand the periodic update of COPD prevalence and its determinants.MethodsEPISCAN II aimed to estimate the prevalence of COPD in the general population aged 40 years or older in all 17 regions of Spain. A random population screening sample, requiring 600 participants per region performed a questionnaire plus post-bronchodilator (post-BD) spirometry.ResultsA total of 12,825 subjects were initially contacted, and 9433 (73.6%) agreed to participate, of whom 9092 performed a valid spirometry. Baseline characteristics were: 52.6% women, mean ± SD age 60 ± 11 years, 19.8% current- and 34.2% former-smokers. The prevalence of COPD measured by post-BD fixed ratio FEV₁/FVC < 0.7 was 11.8% (95% C.I. 11.2–12.5) with a high variability by region (2.4-fold). Prevalence was 14.6% (95% C.I. 13.5–15.7) in males and 9.4% (95% C.I. 8.6–10.2) in females; according to the lower limit of normal (LLN) was 6.0% (95% C.I. 5.5–6.5) overall, by sex being 7.1% (95% C.I. 6.4–8.0) in males and 4.9% (95% C.I. 4.3–5.6) in females. Underdiagnosis of COPD was 74.7%. Cases with COPD were a mean of seven years older, more frequently male, of lower attained education, and with more smokers than the non-COPD population (p < 0.001). However, the number of cigarettes and pack-years in non-COPD participants was substantial, as it was the reported use of e-cigarettes (7.0% vs. 5.5%) (p = 0.045). There were also significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression (all p < 0.001).ConclusionsCOPD remains prevalent in Spain and frequently underdiagnosed.     

Validación pronóstica según los criterios de la GesEPOC 2017

IntroductionThe Spanish COPD guidelines (GesEPOC) have been recently modified. The aim of this study is to assess this revision and evaluate the prognosis of patients according to the new classification of severity.MethodsA total of 700 COPD patients (83.9% men) were prospectively followed up for a mean period of 5 years in tertiary hospitals in Spain and the USA. Anthropometric data, lung function tests, dyspnea (according to the mMRC scale), BODE and Charlson index were collected. We calculated mortality at 5 years following the risk criteria proposed by the new GesEPOC.ResultsMean age was 66 ± 9.6 years and mean FEV₁% was 59.7 ± 20.2. The proportion of patients in the low-risk group was 40.43%. Patients in the high-risk group had a significantly higher BODE index than those in the low-risk group (2.92 ± 0,66 vs. 0.52 ± 1.91, p < 0.001), while the Charlson index score was similar in both groups. Mortality at 60 months was significantly higher in the high-risk group (31.7% vs. 15.5%, p < 0.001). Dyspnea and FEV₁% were also independent predictors of mortality (p < 0.001), and neither was inferior to the risk classification proposed by GesEPOC.ConclusionsThe new severity index proposed by GesEPOC accurately predicts 5-year mortality. However, dyspnea and FEV₁% have the same strength in predicting mortality.     

Benefits of adding fluticasone propionate/salmeterol to tiotropium in COPD: A meta-analysis

ObjectiveThis meta-analysis was performed to evaluate the efficacy and safety of adding fluticasone propionate/salmeterol (FSC) to tiotropium (Tio) in COPD patients.MethodsA systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases, and a hand search of leading respiratory journals. Randomized clinical trials on treatment of stable COPD with the addition of FSC, compared with tiotropium alone, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMD), with 95% confidence interval (CI).ResultsSix trials met the inclusion criteria. Compared with tiotropium, addition of FSC presented significant effects on trough forced expiratory volume in 1 s (FEV₁) (WMD 54.64 mL; 95% CI 51.76 to 57.52 mL; P < 0.001), COPD exacerbations (OR 0.73; 95% CI 0.55 to 0.96; p = 0.03), and health-related quality of life (WMD 4.63; 95% CI 4.26 to 5.01; P < 0.001). No significant increase was noticed in adverse events in the Tio + FSC group (OR 1.24; 95% CI 0.98 to 1.57; p = 0.07).ConclusionsThe addition of FSC to subjects with COPD treated with tiotropium significantly improves lung function, quality of life and COPD exacerbations without increasing the risk of adverse events.     

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

IntroductionThe role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response.MethodsObservational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests.ResultsThe study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p < 0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV₁, FEV₁/FVC and FENO, whereas they were FEV₁/FVC and FENO for mannitol. A FENO value > 26 ppb, FEV1 ≤ 103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value > 26 ppb was enough to correctly classify 81.5% of mannitol responders.ConclusionsOur study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.     

Bronchodilator efficacy of tiotropium–formoterol via single pressurized meter dose inhaler (pMDI) versus tiotropium alone in COPD

BackgroundBronchodilators form the main stay of treatment for COPD. When symptoms are not adequately controlled with one bronchodilator, addition of another bronchodilator is recommended. We have recently developed a combination of tiotropium and formoterol in a single pressurized metered dose inhaler (pMDI) (Cipla Ltd., India). The aim of this study was to compare the bronchodilator effects of a single dose of 18 mcg of tiotropium versus a single dose of a combination of 18 mcg tiotropium plus 12 mcg formoterol administered via a pMDI in subjects with moderate-to-severe COPD.Study design44 COPD subjects were enrolled in this randomized, double-blind, multi-centre, cross-over study. 18 mcg tiotropium and 18 mcg tiotropium plus 12 mcg formoterol were administered via pressurized metered dose inhalers on two separate days. FEV₁, FVC and Inspiratory capacity (IC) were measured before, 15, 30 min, 1, 2, 3, 4, 6, 8, 12 and 24 h after the study drugs were administered.ResultsCompared with tiotropium alone, a combination of tiotropium plus formoterol showed a faster onset of bronchodilator response (p < 0.01 for FEV1 and FVC), a greater mean maximum change in FEV1 (p = 0.01) and FVC (p = 0.008) and greater AUC_0–24h values for FEV₁, FVC and IC. Trough FEV₁ and FVC values were also greater in the combination group.ConclusionA combination of tiotropium plus formoterol administered via a single inhaler produced a superior bronchodilator response than tiotropium alone over a period of 24 h.     

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.     

Post-bronchodilator Reversibility of FEV1 and Eosinophilic Airway Inflammation in COPD

Introduction

The relationship between bronchodilator responsiveness and eosinophilic airway inflammation has not been well documented in COPD. It has been investigated in this retrospective study. This issue has grown in importance due to increasing interest in the asthma-COPD overlap syndrome.