A Race-neutral Approach to the Interpretation of Lung Function Measurements.

Rationale: The use of self-reported race and ethnicity to interpret lung function measurements has historically assumed that the observed differences in lung function between racial and ethnic groups were because of thoracic cavity size differences relative to standing height. Very few studies have considered the influence of environmental and social determinants on pulmonary function. Consequently, the use of race and ethnicity-specific reference equations may further marginalize disadvantaged populations. Objectives: To develop a race-neutral reference equation for spirometry interpretation. Methods: National Health and Nutrition Examination Survey (NHANES) III data (n = 6,984) were reanalyzed with sitting height and the Cormic index to investigate whether body proportions were better predictors of lung function than race and ethnicity. Furthermore, the original GLI (Global Lung Function Initiative) data (n = 74,185) were reanalyzed with inverse-probability weights to create race-neutral GLI global (2022) equations. Measurements and Main Results: The inclusion of sitting height slightly improved the statistical precision of reference equations compared with using standing height alone but did not explain observed differences in spirometry between the NHANES III race and ethnic groups. GLI global (2022) equations, which do not require the selection of race and ethnicity, had a similar fit to the GLI 2012 "other" equations and wider limits of normal. Conclusions: The use of a single global spirometry equation reflects the wide range of lung function observed within and between populations. Given the inherent limitations of any reference equation, the use of GLI global equations to interpret spirometry requires careful consideration of an individual's symptoms and medical history when used to make clinical, employment, and insurance decisions.

Direct healthcare costs associated with management of asthma: comparison of two treatment regimens in Indonesia, Thailand and Vietnam.

OBJECTIVE: Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries. METHODS: A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year). RESULTS: Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31-0.38, MART: 0.24-0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137-£284), £158 (£125-£190), and £151 (£141-£164) for those who used FP/salm, and £242 (£217-£267), £284 (£237-£340) and £266 (£224-£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively. CONCLUSIONS: In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.

Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts.

BACKGROUND AND OBJECTIVE: The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts. METHODS: Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted. RESULTS: Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. CONCLUSIONS: %LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

GINA Implementation Improves Asthma Symptoms Control and Lung Function: A Five-Year Real-World Follow-Up Study.

Symptoms control remains challenging for most patients with asthma. This study was conducted to evaluate the level of asthma symptoms control and lung function over 5 years of GINA (Global INitiative for Asthma) implementation. We included all patients with asthma who had been managed following GINA recommendations at the Asthma and COPD Outpatient Care Unit (ACOCU) of the University Medical Center in Ho Chi Minh City, Vietnam from October 2006 to October 2016. Of 1388 patients with asthma managed following GINA recommendations, the proportion of patients with well-controlled asthma significantly improved from 2.6% at baseline to 66.8% at month 3, 64.8% at year 1, 59.6% at year 2, 58.6% at year 3, 57.7% at year 4, and 59.5% at year 5 (p < 0.0001 for all comparisons). The proportion of patients with persistent airflow limitation significantly decreased from 26.7% at baseline to 12.6% at year 1 (p < 0.0001), 14.4% at year 2 (p < 0.0001), 15.9% at year 3 (p = 0.0006), 12.7% at year 4 (p = 0.0047), and 12.2% at year 5 (p = 0.0011). In patients with asthma managed according to GINA recommendations, asthma symptoms control and lung function improved after 3 months and the improvement was sustained over 5 years.

COPD Patients with Asthma Features in Vietnam: Prevalence and Suitability for Personalized Medicine.

COPD patients with asthma features usually benefit from inhaled corticosteroids (ICS)-containing regimens, but their burden and diagnostic criteria remain to be established. The aims of this study were to estimate the proportion of patients with asthma features among patients with physician-diagnosed COPD and to investigate differences in clinical characteristics and current medications between COPD patients with asthma features and patients with COPD alone. A cross-sectional study was conducted at two respiratory out-patient clinics at the University Medical Center in Ho Chi Minh City and Bach Mai Hospital in Ha Noi, Vietnam. COPD patients with asthma features were identified by attending physicians following the approach recommended by the GINA/GOLD joint committee. Of the 332 patients screened, 300 were enrolled in the study. The proportion of COPD patients with asthma features was 27.3% (95% confidence interval (95% CI) 22.6-32.6%). COPD patients with asthma features were younger, with higher FEV1 values, a greater proportion of positive bronchodilator reversibility tests, higher blood eosinophil count, and were more often treated with ICS/LABA (ICS/long-acting bronchodilator beta-2 agonist) than patients with COPD alone. The prevalence of COPD patients with asthma features is particularly high in Vietnam thus requiring appropriate action plans in clinical practice.

Survey of the management of patients with bronchiectasis: a pilot investigation in Asian populations.

BACKGROUND/AIMS: Although international guidelines for bronchiectasis management have been published in Western countries, there is a lack of data about their application in Asian populations including patients with different phenotypes. We aimed to investigate the current status of bronchiectasis management in Asian populations. METHODS: A nationwide questionnaire survey was performed of Asian respiratory specialists from South Korea, Japan, Taiwan, Singapore, Vietnam, and Sri Lanka. Participants were invited by e-mail to answer a questionnaire comprising 25 questions based on international guidelines for the management of bronchiectasis. RESULTS: A total of 221 physicians participated in the survey. About half of them were Korean (50.2%), with the next most common nationalities being Japanese (23.1%), Taiwanese (13.6%), and Singaporean (7.7%). Only 18 (8.1%) responders had local guidelines for bronchiectasis. While 85 (38.5%) responders checked sputum acid-fast bacillus smear/culture about 1 to 3 times per year, only a small proportion of responders routinely performed a serum immunoglobulin test (36/221, 16.3%) or evaluated for allergic bronchopulmonary aspergillosis (41/221, 18.6%). Less than half (43.4%) of responders performed eradication treatment in patients with drug-sensitive Pseudomonas aeruginosa infection, mainly due to the limited availability of inhaled antibiotics (34.8%). In addition, 58.6% of responders considered physiotherapy such as airway clearance and pulmonary rehabilitation. CONCLUSION: Discrepancies might exist between guideline recommendations and practice for bronchiectasis management in Asian populations, partly due to the limited availability of treatment in each country. The development of local guidelines that consider the phenotypes and situation will help to standardize and improve the management of bronchiectasis.

Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases.

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.

Helsinki by nature: The Nature Step to Respiratory Health.

BACKGROUND: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. RESULTS: The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking "nature" to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. CONCLUSIONS: In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory.

Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. METHODS: One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. RESULTS: Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. CONCLUSIONS: The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD.

Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia population-based survey.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a clinical syndrome encompassing a group of chronic, progressive, and debilitating respiratory conditions, that are characterized by incompletely reversible airflow limitation. Within the Asia-Pacific region, prevalence estimates have been derived using various protocols and study methods, and there is little data on the impact of COPD exacerbations. This study aimed to provide a comprehensive picture of the current prevalence and burden of COPD in this region. METHODS: A population-based survey was conducted in nine Asia-Pacific territories between 01 February 2012 and 16 May 2012. Overall, 112,330 households were screened to identify eligible subjects (aged ≥40 years, with a physician diagnosis of COPD, chronic bronchitis or emphysema, or with identifiable symptoms of chronic bronchitis). Out of a sample of 69,279 individuals aged ≥40 years, 4,289 subjects with COPD were identified. Data were collected via face-to-face interviews or by fixed-line telephone, using a structured questionnaire. A total of 1,841 completed questionnaires were analyzed. RESULTS: The overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD. In the 12 months prior to the survey, nearly half of all subjects (46%) had experienced exacerbations, and 19% had been hospitalized as a result of their condition. When subjects were asked about the impact of their condition on employment, 23% said their condition kept them from working, and 42% felt that their condition limited their ability to work or their activities. Of those who reported taking prescription drugs, 20% did not know the name of the drugs they were taking. Prescription of oral corticosteroids was common, with 44% of subjects having used these during the previous year to manage their respiratory symptoms; in contrast, inhaler use was low (25%). Only 37% of subjects had taken a lung function test, and the majority (89%) of those tested did not know their test results. CONCLUSIONS: Across the Asia-Pacific territories surveyed, the prevalence of COPD is high, indicating a substantial socioeconomic burden. Our findings suggest that there is considerable room for improvement in the management of COPD, and highlight a need to enhance patient and physician education in the region.

A mixed phenotype of airway wall thickening and emphysema is associated with dyspnea and hospitalization for chronic obstructive pulmonary disease.

RATIONALE: Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype. OBJECTIVES: To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS: Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression. MEASUREMENTS AND MAIN RESULTS: Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P < 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1. CONCLUSIONS: Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.

Airway wall area derived from 3-dimensional computed tomography analysis differs among lung lobes in male smokers.

BACKGROUND: It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers. METHODS: Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe. RESULTS: Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R(2) = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not. CONCLUSION: In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.

Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients. METHODS: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life. RESULTS: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV(1)], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George's Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV(1), P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006). CONCLUSION: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.

Gaps in capacity in primary care in low-resource settings for implementation of essential noncommunicable disease interventions.

Objective. The objective was to evaluate the capacity of primary care (PC) facilities to implement basic interventions for prevention and management of major noncommunicable diseases (NCDs), including cardiovascular diseases and diabetes. Methods. A cross-sectional survey was done in eight low- and middle-income countries (Benin, Bhutan, Eritrea, Sri Lanka, Sudan, Suriname, Syria, and Vietnam) in 90 PC facilities randomly selected. The survey included questions on the availability of human resources, equipment, infrastructure, medicines, utilization of services, financing, medical information, and referral systems. Results and Conclusions. Major deficits were identified in health financing, access to basic technologies and medicines, medical information systems, and the health workforce. The study has provided the foundation for strengthening PC to address noncommunicable diseases. There are important implications of the findings of this study for all low- and middle-income countries as capacity of PC is fundamental for equitable prevention and control of NCDs.