COPD Exacerbation Frequency,Pharmacotherapy and Resource Use: An Observational Study in UK Primary Care

Chronic Obstructive Pulmonary Disease (COPD) management represents a significant health resource use burden. Understanding of current resource use, treatment strategies and outcomes can improve future COPD management, for patient benefit and to aid efficient service delivery. This study aimed to describe exacerbation frequency, pharmacotherapy and health resource use in COPD management in routine UK primary care. A retrospective, observational study using routine clinical records of 511 patients with COPD, was undertaken in 10 General Practices in England. Up to 3 years’ patient data were collected and analysed. 75% (234/314) patients with mild-moderate COPD (≥50% predicted FEV₁) received inhaled corticosteroids (ICS). 11% of patients (54/511) received ICS monotherapy. Mean (standard deviation) annual exacerbation frequency was 1.1 (1.2) in mild-moderate, 1.7 (1.6) in severe (30–49% predicted FEV₁) and 2.2 (2.0) in very severe (<30% predicted FEV₁) COPD. 14% patients (69/511) had a mean exacerbation frequency of ≥3/year (‘frequent-exacerbators’); 9% (27/314) of patients with mild-moderate, 19% (27/145) with severe and 29% (15/52) with very severe COPD. 14% (10/69) of frequent-exacerbators failed to receive inhaled long-acting beta agonists (LABA), 25% (17/69) inhaled long-acting muscarinic antagonists (LAMA), and 12% (`/69) ICS. Frequent-exacerbators had a median of 6.67 primary care contacts/year, 1.0 secondary care visits/year and 21% were hospitalised for COPD/year. Inhaled therapy was frequently inappropriate, with over-use of ICS in patients with mild-moderate COPD. COPD exacerbations were associated with high health resource use and occurred at all levels of disease severity. COPD management strategies should encompass risk-stratification for both exacerbation frequency and physiological impairment.     

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.     

Efficacy of tiotropium in COPD patients from Asia: a subgroup analysis from the UPLIFT trial

Background and objective: Studies in respiratory diseases other than chronic obstructive pulmonary disease suggest potentially differing responses to medications among patients from different regions. We report a subgroup analysis of patients recruited to Asian centres from a previously reported 4‐year COPD trial. Methods: Subgroup analysis from a randomized, double‐blinded, placebo‐controlled trial of tiotropium 18 µg daily in COPD. Primary end‐point was rate of decline in FEV₁. Secondary end‐points included spirometry at individual time points, health‐related quality of life (St George's Respiratory Questionnaire), exacerbations and mortality. Results: Of 5992 patients, 362 were from Asian centres (100 from Japan). Mean age 66 years, 95% men, 13% current smokers, BMI: 21 kg/m²; post‐bronchodilator FEV₁: 44% predicted; St George's Respiratory Questionnaire total score: 44 units. No treatment effect was observed for rate of decline in FEV₁ although annual decline was less in Asian patients. Morning pre‐bronchodilator FEV₁ and forced vital capacity improved in Asian patients (P < 0.05). Tiotropium reduced number of exacerbations (rate ratio (95% confidence interval (CI)): 0.73 (0.57–0.94)). Hazard ratios (95%CI) for exacerbations and hospitalized exacerbations (tiotropium/control) were 0.81 (0.62–1.05) and 0.85 (0.61–1.19), respectively. St George's Respiratory Questionnaire total score improved by 1.5–6.1 units (P < 0.05 for months 18, 24, 30 and 36) with tiotropium. Fatal events occurred in 34 tiotropium (18.5%) and 42 control (23.6%) patients. Conclusions: In COPD patients from Asia, tiotropium improves lung function, improves health‐related quality of life and reduces exacerbations over 4 years of treatment.     

Emergency Hospital Care for Exacerbation of COPD: Is Inhaled Maintenance Therapy Modified?

Background: The impact of hospital emergency care and inward admission for acute exacerbations of COPD on inhaled maintenance treatment is not well known. Objective: Therefore, we evaluated the impact of short-stay emergency hospital care and inward admission for acute exacerbation of COPD (eCOPD) on inhaled maintenance treatment prescribed at discharge. Design: Prospective observational cohort study of patients presenting with eCOPD at emergency departments in 16 hospitals of the Spanish healthcare system. The ethics committee at each hospital approved the study and patients provided an informed consent before inclusion. We classified the patients according to the severity of COPD: mild/moderate (FEV₁ ≥ 50% predicted) or severe/very severe (FEV₁ < 50% predicted) and need of inward hospitalisation. We analysed changes to maintenance treatment on discharge according to GOLD strategy. Results: 1559 patients, 65% required hospitalisation. The most common maintenance treatment was inhaled corticoids (ICS) (80.9%) followed by long-acting beta-agonists (LABA) (75.4%). The most common combination was triple therapy (LABA+ LAMA+ICS) (56.2%) followed by LABA+ICS dual therapy (18.2%) regardless of the severity of COPD. In more than 60% of patients treatment was not changed at discharge. The most common change in treatment was a reduction when discharge was from emergency care and an increase after hospitalisation (-21.6% and +19.5% in severe/very severe COPD, respectively). Conclusions: Emergency hospital care for eCOPD does not usually induce changes in inhaled maintenance treatment for COPD regardless of the duration of the hospital stay.     

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.     

Patients with mild-to-moderate asthma may develop clinically significant chronic obstructive pulmonary disease

Background and objective: Little is known about the aetiology and clinical characteristics of COPD among people who have never smoked. Methods: A case–control study was conducted to describe the potential risk factors for clinically significant COPD among smokers and people who had never smoked. Medical record reviews and scoring of high‐resolution computed tomography (HRCT) findings were performed in patients with clinically significant COPD (defined as having post‐bronchodilator FEV₁/FVC < 0.7 and FEV₁ < 60% of the predicted values). Pathological analyses were performed in some patients following autopsy. Results: Among the 9493 subjects screened, 424 (4.5%) were diagnosed with clinically significant COPD. Forty‐nine (11.6% of clinically significant COPD) were never smokers (NSCOPD), and a comparative group of 98 smoking patients with COPD was randomly selected (SMCOPD). NSCOPD was characterized by predominantly female sex (87.8%) and a high prevalence of physician‐diagnosed asthma (61.2%). Similar levels of reduction in %FEV₁ and %FEF_25–75% were found in NSCOPD and SMCOPD, but there were higher %DL_CO values and fewer low attenuation areas on HRCT in NSCOPD. More than half of the NSCOPD patients without a history of asthma had features of asthma. More than one‐third of NSCOPD patients with an asthma history had never had a severe attack. At autopsy, both NSCOPD and SMCOPD showed wall thickening and inflammatory cell infiltration in small airways, and the number of CD4⁺‐T cells was increased in NSCOPD. Conclusion: In elderly Japanese, COPD among never smokers is largely attributable to asthma. Airflow limitation in NSCOPD results from small airway disease (airway predominant phenotype) rather than parenchymal destruction (emphysematous phenotype).     

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.     

Long‐acting muscarinic antagonist + long‐acting beta agonist versus long‐acting beta agonist + inhaled corticosteroid for COPD: A systematic review and meta‐analysis

Some trials have been conducted to compare long‐acting muscarinic antagonist (LAMA) + long‐acting beta agonist (LABA) versus LABA + inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), but no meta‐analysis were reported. Two investigators independently searched for eligible articles using the PubMed, Web of Science and Cochrane databases. Articles in authors' reference files were also regarded as candidates. The eligibility criteria for the current meta‐analysis were original trials written in English comparing the impact of LAMA + LABA and LABA + ICS for COPD patients. A pooled value for the continuous value was calculated using the genetic inverse variance method for mean difference. Incidence of events was evaluated using the odds ratio (OR). Minimal clinically important difference were 50 mL for forced expiratory volume in 1 s (FEV₁), four points for St George Respiratory Questionnaire (SGRQ) and one point for transition dyspnoea index (TDI). We included seven randomized controlled trials and one cross‐over trial with follow‐up period of 6–26 weeks. Compared with LABA + ICS, LAMA + LABA led to significantly greater improvements of trough FEV₁ by 71 (95% CI: 48–95) mL, TDI by 0.38 points (95% CI: 0.17–0.58), less exacerbations with an OR of 0.77 (95% CI: 0.62–0.96) and less pneumonia with an OR of 0.28 (95% CI: 0.12–0.68). Frequencies of any adverse event, serious adverse event, adverse event leading to discontinuation, all‐cause death and change of total score of SGRQ were not different in both arms. LAMA + LABA might be a better option for treating COPD than LABA + ICS.     

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.     

Detection and prevalence of chronic obstructive pulmonary disease in a cardiovascular clinic: evaluation using a hand held FEV₁/FEV₆ meter and questionnaire

Background and objective: COPD is one of the leading causes of morbidity and mortality worldwide, and its prevalence continues to increase. Although spirometry is indispensable for the diagnosis of COPD, other simple and reliable tools are necessary for screening of COPD because spirometry is not widely available. This study investigated the usefulness of a combination of an electronic FEV₁/FEV₆ meter (PiKo‐6) with a COPD questionnaire as a screening method in patients with cardiovascular diseases. Methods: The PiKo‐6 and the COPD questionnaire of the International Primary Care Airways Group were used to screen patients attending a cardiovascular outpatient clinic. Patients with FEV₁/FEV₆ < 70% were defined as having airflow limitation. Patients diagnosed with airflow limitation underwent spirometry. Using data from the PiKo‐6 and the COPD questionnaire, patients were assigned to a COPD group or a non‐COPD group. The relationship between PiKo‐6 measurements and spirometry was also evaluated. Results: Among 753 patients, 82 (10.9%) showed airflow limitation when assessed with the PiKo‐6. Of these patients, 79 (10.5%) were assigned to the COPD group. FEV₁, FEV₆ and FEV₁/FEV₆, as measured with the PiKo‐6, correlated significantly with FEV₁, FVC and FEV₁/FVC, respectively, as measured by spirometry (r = 0.865, 0.751 and 0.57). Among the cardiovascular comorbidities, heart failure and ischaemic heart disease showed slightly stronger associations with airflow limitation (13.8% and 12.5%, respectively). Conclusions: Combination of the PiKo‐6 with a COPD questionnaire may be a useful and feasible method of identifying undiagnosed COPD patients attending a cardiovascular outpatient clinic.     

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.     

Association among fraction of exhaled nitrous oxide,bronchodilator response and inhaled corticosteroid type

BACKGROUND:Fraction of exhaled nitrous oxide (FeNO) is a known marker of airway inflammation and a topic of recent investigation for asthma control in children.OBJECTIVE:To investigate the relationship among FeNO and bronchodilator response measured by spirometry and types of inhaled corticosteroids (ICS).METHODS:A one-year review of children tested with spirometry and FeNO in a regional pediatric asthma centre was conducted.RESULTS:A total of 183 children were included (mean [± SD] age 12.8±2.8 years). Fluticasone was used most commonly (n=66 [36.1%]), followed by ciclesonide (n=50 [27.3%]). Most children (n=73 [39.9%]) had moderate persistent asthma. Increased FeNO was associated with percent change in forced expiratory volume in 1 s (FEV₁) after bronchodilator adjusted for allergic rhinitis, parental smoking and ICS type (B=0.08 [95% CI 0.04 to 0.12]; P<0.001). Similarly, FeNO was associated with percent change in forced expiratory flow at 25% to 75% of the pulmonary volume (FEF_25–75) after bronchodilator adjusted for parental smoking and ICS type (B=0.13 [95% CI 0.01 to 0.24]; P=0.03). FeNO accounted for only 16% and 9% of the variability in FEV₁ and FEF_25–75, respectively. Mean-adjusted FeNO was lowest in fluticasone users compared with no ICS (mean difference 18.6 parts per billion [ppb] [95% CI 1.0 to 36.2]) and there was no difference in adjusted FeNO level between ciclesonide and no ICS (5.9 ppb [95% CI −9.0 to 20.8]).CONCLUSION:FeNO levels correlated with bronchodilator response in a regional pediatric asthma centre. However, FeNO accounted for only 16% and 9% of the variability in FEV₁ and FEF_25–75, respectively. Mean adjusted FeNO varied according to ICS type, suggesting a difference in relative efficacy between ICS beyond their dose equivalents.     

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)     

The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden--the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study

Objectives: To estimate chronic obstructive pulmonary disease (COPD) prevalence in Uppsala and the impact of risk factors on disease prevalence using the standardised methods of the Burden of Obstructive Lung Disease (BOLD) study initiative. Methods: Randomly selected participants, aged 40 years or more (n = 548) responded to a questionnaire regarding smoking habits, respiratory symptoms, medical history, and exposure to airway irritants. Spirometry, with a post‐bronchodilator test, was performed and COPD defined as post‐bronchodilatory forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 0.70 or FEV₁/FVC < lower limit of normality (LLN). Circulatory inflammatory markers were measured. Results: COPD prevalence was 16.2%, which was the fourth lowest prevalence of COPD, compared with 12 other BOLD centres. Main risk factors for COPD were increasing age [odds ratio (OR) = 2.08 per 10 years] and smoking (OR = 1.33 per 10 pack years). Higher education was protective (OR = 0.70 per 5 years). Previous tuberculosis was an almost significant risk factor for COPD (P = 0.08). Subjects with COPD reported more respiratory symptoms but only 29% had previous doctor diagnosed COPD, asthma, chronic bronchitis or emphysema. Participants with COPD had higher levels of C‐reactive protein (P = 0.01), but no difference was observed in interleukin 6 (IL‐6) levels. Using LLN instead of the fixed FEV₁/FVC ratio reduced the prevalence of COPD to 10%. Conclusion: COPD prevalence in Uppsala was similar to other BOLD centres in high‐income countries. Apart from known COPD risk factors (age, smoking, lower educational level), a history of tuberculosis may be associated with COPD even in high‐income countries. COPD remains under‐diagnosed, as only 29% of subjects with COPD had a previously diagnosed lung disorder. Please cite this paper as: Danielsson P, Ólafsdóttir IS, Benediktsdóttir B, Gíslason T and Janson C. The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden – the Burden of Obstructive Lung Disease (BOLD) study: cross‐sectional population‐based study. Clin Respir J 2012; 6: 120–127.     

A new staging strategy for chronic obstructive pulmonary disease

Background:

The best method for expressing lung function impairment is undecided. We tested in a population of patients with chronic obstructive pulmonary disease (COPD) whether forced expiratory volume in 1 second (FEV₁) or FEV₁ divided by height squared (FEV₁/ht²) was better than FEV₁ percent predicted (FEV₁PP) for predicting survival.

Method:

FEV₁, FEV₁PP, and FEV₁/ht² recorded post bronchodilator were compared as predictors of survival in 1095 COPD patients followed for 15 years. A staging system for severity of COPD was defined from FEV₁/ht² and compared with the Global Initiative for Obstructive Lung Disease (GOLD) staging system.

Result:

FEV₁/ht² was a better univariate predictor of survival in COPD than FEV₁ and both were better than FEV₁PP. The best multivariate model for predicting survival included FEV₁/ht², age and sex. Comparing the GOLD stages with the FEV₁/ht² groups found that survival was more coherent within each FEV₁/ht group than it was within each GOLD stage. FEV₁/ht² had 60% more people in its most severe group than the severest GOLD stage with these extra subjects having equivalently poor survival and had 155% more in the least severe group with equivalent survival. GOLD staging misclassified 51% of subjects with regard to survival.

Conclusion:

We conclude that GOLD criteria using FEV₁PP do not optimally stage COPD with regard to survival. An alternative strategy using FEV₁/ht² improves the staging of this disease. Studies which stratify COPD patients to determine the effect of interventions such as drug trials, rehabilitation, or management guidelines should consider alternatives to the GOLD classification.     

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.     

Chronic obstructive pulmonary disease in the absence of chronic bronchitis in China

Background and objective: COPD has a variable natural history and not all individuals follow the same course. The aim of this study was to assess the prevalence of COPD in the absence of chronic bronchitis (CB) based on a population survey in China, and to identify the determinants of CB in patients with COPD. Methods: A multi‐stage cluster sampling strategy was used to survey a population from seven different provinces/cities of China. All residents over 40 years of age were interviewed using a standardized questionnaire and spirometry was measured. A post‐bronchodilator FEV₁/FVC < 70% was defined as the diagnostic criterion for COPD. All COPD patients who were screened were divided into two groups according to the presence or absence of CB. Results: Of the population of 20 245 that was surveyed, 70% of the 1668 patients who were diagnosed with COPD reported no history of CB. The ages, BMI and comorbidities of COPD patients with or without CB were similar. Male gender, residence in a rural area, having a lower level of education, exposure to tobacco smoke or biomass fuels, poor ventilation in the kitchen and a family history of respiratory disease were all associated with a higher risk of COPD with CB. Patients without CB had less difficulty in walking and higher FEV₁/FVC values than patients with CB, but were more likely to be underdiagnosed. The strongest predictors of CB were male gender, current smoking and severity of dyspnoea. Conclusions: This survey confirmed that there is a high prevalence of COPD in the absence of CB in China. It appears that CB is not essential to the diagnosis of COPD.     

Efficacy and safety of indacaterol 150 and 300 µg in chronic obstructive pulmonary disease patients from six Asian areas including Japan: a 12-week, placebo-controlled study

Background and objective: The efficacy and safety of indacaterol, a novel inhaled once daily ultra long‐acting β₂‐agonist was evaluated in COPD patients in six Asian countries/areas. This study was primarily designed to obtain the regulatory approval of indacaterol in Japan. Methods: Moderate‐to‐severe COPD patients were randomized to indacaterol 150 µg, indacaterol 300 µg or placebo once daily. Efficacy variables: trough FEV₁ (average of 23 h 10 min and 23 h 45 min post‐dose values), health status (St. George's Respiratory Questionnaire) and transition dyspnoea index at week 12. Safety/tolerability was evaluated. Results: A total of 347 patients were randomized (96.5% male, mean (SD) age 66.7 (8.38) years, post‐bronchodilator FEV₁% predicted: 53.7 (12.50)); 88.8% completed. The least squares means (LSM) trough FEV₁ at week 12 for indacaterol 150 µg, indacaterol 300 µg and placebo were 1.34 L, 1.37 L and 1.17 L, respectively, with differences versus placebo exceeding the prespecified minimal clinically important difference of 0.12 L (0.17 L and 0.20 L for indacaterol 150 µg and 300 µg, respectively, both P < 0.001). The week 12 LSM transition dyspnoea index score was statistically superior for both indacaterol doses versus placebo (differences of 1.30 and 1.26, P < 0.001; both exceeding the minimal clinically important difference of 1). At week 12, both indacaterol doses provided statistically significant (P ≤ 0.005) and clinically meaningful (≥4 units) improvements in LSM St. George's Respiratory Questionnaire total score versus placebo (differences: ?4.8 and ?5.7 units). Adverse events for indacaterol (49.1%, both doses) were lower than placebo (59.0%) and were mostly mild/moderate in severity; no deaths were reported. Conclusions: Indacaterol provided clinically significant bronchodilation and improvements in dyspnoea and health status in Asian COPD patients.     

Reanalysis of the Japanese experience using the combined COPD assessment of the 2011 GOLD classification

BackgroundThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 consensus report proposed a new classification system, incorporating symptoms with future risk, in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized it could be applied to Japanese COPD patients.MethodsWe previously analyzed clinical factors related to 5-year mortality in 150 male outpatients with COPD. We reviewed the data and reanalyzed the relationships between the new GOLD classification and various outcomes including mortality.ResultsThere were 51 (34.0%), 12 (8.0%), 57 (38.0%), and 30 (20.0%) patients in GOLD A (forced expiratory volume in 1 s [FEV₁]≥50% predicted and modified Medical Research Council [mMRC] 0–1), GOLD B (FEV₁≥50% predicted and mMRC≥2), GOLD C (FEV₁<50% predicted and mMRC 0–1), and GOLD D (FEV₁ <50% predicted and mMRC≥2), respectively. The GOLD 2011 classification correlated significantly with exercise capacity and multi-dimensional disease staging. Cox proportional hazards analysis revealed that, among several methods categorizing symptoms, the GOLD A-D classification was significantly associated with mortality (p=0.0055).ConclusionAlthough the relative number of patients in each category of the combined COPD assessment classification depended on the choice of symptom measures, the categories defined by the mMRC scale (score 0–1 versus ≥2) were most useful for future risk assessed as mortality. GOLD A had the lowest mortality, followed by GOLD B and C, and D had the highest mortality. Exercise capacity was also stratified by the new GOLD classification.