The availability, cost, and affordability of essential medicines for asthma and COPD in low-income and middle-income countries: a systematic review.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) cause a considerable burden of morbidity and mortality in low-income and middle-income countries (LMICs). Access to safe, effective, quality-assured, and affordable essential medicines is variable. We aimed to review the existing literature relating to the availability, cost, and affordability of WHO's essential medicines for asthma and COPD in LMICs. METHODS: A systematic review of the literature was done by searching seven databases to identify research articles published between Jan 1, 2010, and June 30, 2022. Studies on named essential medicines for asthma and COPD in LMICs were included and review articles were excluded. Two authors (MS and HT) screened and extracted data independently, and assessed bias using Joanna Briggs Institute appraisal tools. The main outcome measures were availability (WHO target of 80%), cost (compared with median price ratio [MPR]), and affordability (number of days of work of the lowest paid government worker). The study was registered with PROSPERO, CRD42021281069. FINDINGS: Of 4742 studies identified, 29 met the inclusion criteria providing data from 60 LMICs. All studies had a low risk of bias. Six of 58 countries met the 80% availability target for short-acting beta-agonists (SABAs), three of 48 countries for inhaled corticosteroids (ICSs), and zero of four for inhaled corticosteroid-long-acting beta-agonist (ICS-LABA) combination inhalers. Costs were reported by 12 studies: the range of MPRs was 1·1-351 for SABAs, 2·6-340 for ICSs, and 24 for ICS-LABAs in the single study reporting this. Affordability was calculated in ten studies: SABA inhalers typically cost around 1-4 days' wages, ICSs 2-7 days, and ICS-LABAs at least 6 days. The included studies showed heterogeneity. INTERPRETATION: Essential medicines for treating asthma and COPD were largely unavailable and unaffordable in LMICs. This was particularly true for inhalers containing corticosteroids. FUNDING: WHO and Wellcome Trust.

Physical Activity Levels and Associated Factors in a Latin American COPD Population of Patients. The LASSYC Study.

Reduced physical activity (PA) is an independent risk factor for lung function decline, hospitalization and mortality in chronic obstructive pulmonary disease (COPD) and affects a large proportion of patients from Europe and the United States. However, little is known of the level of PA of COPD patients in Latin America. The aim of this study was to provide information of the level of PA and its determinants in COPD patients in Latin America. This is an observational, cross-sectional study on patients with COPD in seven Latin American countries. PA level was evaluated with the short version of the International Physical Activity Questionnaire (IPAQ) and the association between PA and other variables was investigated. Complete information of PA level was obtained in 734 COPD patients consecutively recruited from specialized outpatient clinics; 448 (61%) were men, with a mean age of 69.6 years (standard deviation [SD] = 8.7) and a mean FEV1 (% predicted) = 49.1% (17.5%). In 37.9% the level of PA was low, and the average sitting time was 36.1 h per week. Patients with low levels of PA were older, with higher levels of dyspnea and higher CAT scores. Additionally, we found that patients with low level of PA presented more symptoms during the day. Low levels of PA have been observed in a large proportion of COPD patients of Latin America, which is higher in women and older patients and it is related with worse functional and clinical characteristics.

Outcomes for symptomatic non-obstructed individuals and individuals with mild (GOLD stage 1) COPD in a population based cohort.

BACKGROUND: We aimed to study the adverse outcomes of symptomatic and asymptomatic non-obstructed individuals and those with mild COPD longitudinally in participants from three Latin-American cities. METHODS: Two population-based surveys of adults with spirometry were conducted for these same individuals with a 5- to 9-year interval. We evaluated the impact of respiratory symptoms (cough, phlegm, wheezing or dyspnea) in non-obstructed individuals, and among those classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1, COPD on exacerbation frequency, mortality and FEV1 decline, compared with asymptomatic individuals without airflow obstruction or restriction. RESULTS: Non-obstructed symptomatic individuals had a marginal increased risk of mortality (HR 1.3; 95% CI 0.9-1.94), increased FEV1 decline (-4.5 mL/year; 95% CI -8.6, -0.4) and increased risk of 2+ exacerbations in the previous year (OR 2.6; 95% CI 1.2-6.5). Individuals with GOLD stage 1 had a marginal increase in mortality (HR 1.5; 95% CI 0.93-2.3) but a non-significant impact on FEV1 decline or exacerbations compared with non-obstructed individuals. CONCLUSIONS: The presence of respiratory symptoms in non-obstructed individuals was a predictor of mortality, lung-function decline and exacerbations, whereas the impact of GOLD stage 1 was mild and inconsistent. Respiratory symptoms were associated with asthma, current smoking, and the report of heart disease. Spirometric case-finding and treatment should target individuals with moderate-to-severe airflow obstruction and those with restriction, the groups with consistent increased mortality.

Asthma COPD Overlap Syndrome: An Approach to A Real -World Endotype in Obstructive Lung Disease?

BACKGROUND: Although some patients with obstructive lung disease (OLD) have features of both asthma and chronic obstructive pulmonary disease (COPD), the term "asthma-COPD overlap syndrome (ACOS)" was coined only relatively recently. However, there are gaps in our knowledge of the clinical features, pathogenesis, prognosis, and management of ACOS patients. OBJECTIVES: To review the literature on ACOS to determine the extent to which the clinical features, pathologic mechanisms, clinical outcomes, and current therapeutic approaches for ACOS differ from those in patients with asthma alone or COPD alone. METHODS: PUBMED searches were conducted to review the demographic and clinical features, comorbidities, lung imaging characteristics, prognoses, pathologic mechanisms, and current therapeutic approaches for patients with ACOS versus asthma alone or COPD alone. RESULTS: Criteria that are used to diagnose ACOS vary considerably. Overall, ACOS patients have higher symptom burdens (especially dyspnea), poorer quality of life scores, and more frequent and severe exacerbations than patients with COPD alone or asthma alone. However, there are conflicting reports on the prognosis of ACOS patients. Imaging studies indicate that ACOS is predominantly an airway disease. ACOS has been linked to the presence of Th2-type immune responses in COPD airways and Th1-type immune responses in asthmatic airways. Current therapeutic options for ACOS patients include inhaled corticosteroids and bronchodilators. However, randomized clinical trials have not yet been conducted to optimize the management of ACOS patients. CONCLUSION: ACOS patients have clinical features that are now well defined, but additional studies are needed to provide novel insights into ACOS pathogenesis, and to optimize the treatment of these patients.

FEV1 is a better predictor of mortality than FVC: the PLATINO cohort study.

OBJECTIVE: To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort. MATERIALS/PATIENTS AND METHODS: Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively. Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Cox regression was used for analyses. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden's index were calculated. RESULTS: Main causes of death were cardiovascular, respiratory and cancer. Baseline COPD was associated with overall mortality (HR = 1.43 for FEV1/FVC

Perceptions of short and long sleep duration and comorbid conditions: the PLATINO study.

OBJECTIVES: We aimed to describe the distribution of self-reported sleep duration in adults over the age of 40 years and to analyze the associated risk factors, comorbid conditions, and quality of life (QoL). METHODS: Our study was constructed as a cross-sectional population-based study and is part of the PLATINO (Spanish acronym for the Latin American Project for Research in Pulmonary Obstruction) study. It includes data from Mexico City (Mexico), Montevideo (Uruguay), Santiago (Chile), and Caracas (Venezuela). Data from 4533 individuals were analyzed using a single questionnaire entitled, PLATINO, which was designed to collect data on self-reported sleep symptoms. Spirometry also was performed in accordance with international standards. All statistical analyses took the study design into consideration with adjustments for each city. RESULTS: The prevalence of subjects who reported sleeping <7h was 38.4%, ≥ 7 to <9h was 51.4%, and ≥ 9h was 10.2%. In the multivariate analysis, individuals with shorter sleep duration had higher frequencies of insomnia, increased forced expiratory volume in one second in liters and percentage/forced vital capacity in liters (FEV1/FVC) of predicted ratios, and a higher presence of coughing and phlegm. The main risk factor associated with longer duration of sleep was the number of comorbidities. CONCLUSIONS: Self-reported sleep duration discriminated among groups that differed in sleep-related symptoms, respiratory symptoms, QoL and comorbid conditions.

Quality assessment of asthma clinical practice guidelines: a systematic appraisal.

BACKGROUND: The quality and potential impact of available clinical guidelines for asthma management have not been systematically evaluated. We, therefore, evaluated the quality of clinical practice guidelines (CPGs) for asthma. METHODS: We performed a systematic search of scientific literature published between 2000 and 2010 to identify and select CPGs related to asthma management. We searched guideline databases, guideline developers' websites, and the MEDLINE database of the US National Library of Medicine. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines Research & Evaluation (AGREE) II instrument. We calculated the overall agreement among reviewers with the intraclass correlation coefficient (ICC). RESULTS: Eighteen CPGs published between the years 2000 and 2010 were selected from a total of 1,005 references. The overall agreement among reviewers was moderate (ICC: 0.78; 95% CI, 0.62-0.90). The mean scores for each AGREE domain were: scope and purpose, 44.1% (range: 10.0%-79.0%); stakeholder involvement, 33.8% (range: 4.0%-66.0%); rigor of development, 32.4% (range: 8.0%-64.0%); clarity and presentation, 52.1% (range: 17.0%-85.0%); applicability, 21.1% (range: 3%-55%); and editorial independence, 25% (range: 0%-58%). None of the appraised guidelines had a score > 60% (recommended). One-half of the appraised guidelines were recommended with modifications (nine of 18) or not recommended (nine of 18) for use in clinical practice. We observed improvement over time in overall quality of the guidelines (P = .01; guidelines published in the period 2001-2006 vs 2007-2009). CONCLUSIONS: The quality of guidelines for asthma care is low, although it has improved over time. Greater efforts are needed to provide high-quality guidelines that can be used as reliable tools for clinical decision-making in this field.

The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study.

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes. Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥ 2 yrs. Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations. Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.

Insulating diamond particles as substrate for Pd electrocatalysts.

The suitability of insulating highly crystalline diamond particles as support for Pd based electrocatalysts is explored for the first time by evaluating the electrochemical stripping of CO and oxidation of formic acid in acid solutions.

[Lactate dehydrogenase isozymes in skeletal muscle of patients with chronic obstructive pulmonary disease]. / Isoenzimas de lactatodeshidrogenasa en el músculo esquelético de pacientes con EPOC.

INTRODUCTION AND OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH(4) and LDH(5) are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. PATIENTS AND METHODS: Eighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. RESULTS: Controls and patients had similar concentrations of total LDH (mean [SE], 130 [30]micromol/min/g vs 152 [50]micromol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH(1), LDH(2), and LDH(3), with decreased LDH(5) levels; these patients were women and had a lower oxygen saturation. The LDH(5) level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH(3) and LDH(4) concentrations whereas type IIX fibers were inversely correlated with LDH(3) concentration. CONCLUSION: Measurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism.

Prevalence of sleep related symptoms in four Latin American cities.

STUDY OBJECTIVES: to estimate the prevalence of the most common sleep related symptoms (SRS) in the metropolitan areas of Mexico City, Montevideo (Uruguay), Santiago (Chile), and Caracas (Venezuela). METHODS: The study consisted of a multistage cluster sampling of adults aged > or = 40 years living in metropolitan areas. All participants completed a questionnaire on sleep related symptoms. Simplified respiratory polygraphy during sleep was conducted on 188 subjects from Mexico City. Obstructive sleep apnea syndrome was defined as Epworth Sleepiness Scale score > or = 11 and respiratory disturbance index (RDI) > or = 15 events/h; a cut-off of 15 was chosen because of its high sensitivity and specificity in association with the portable monitor used in the study. RESULTS: The study included 4,533 subjects (1,062 in Mexico City, 941 in Montevideo, 1,173 in Santiago, and 1,357 in Caracas). Snoring was reported by 60.2% (95% CI 58.8% to 61.6%), excessive daytime sleepiness by 16.4% (15.3% to 17.5%), observed apneas by 12.3% (11.4% to 13.3%), insomnia by 34.7% (33.3% to 36%), sedative use by 15.1% (14.1% to 16.2%), daytime napping by 29.2% (27.7% to 30.6%), and a combination of snoring, sleepiness, and observed apneas by 3.4% (2.9% to 4%). Men had a higher frequency of snoring and daytime napping, whereas women reported more insomnia and sedative use. Prevalence of OSAS varied from 2.9% among subjects who denied snoring, excessive daytime sleepiness, and observed apneas, to 23.5% among those reporting these 3 symptoms. CONCLUSIONS: A high prevalence of sleep related symptoms and undiagnosed obstructive sleep apnea in Latin America was observed.

Impact of bronchodilator use on the prevalence of COPD in population-based samples.

The aim of this study was to describe the impact of using bronchodilators on the prevalence of Chronic Obstructive Pulmonary Disease in a population-based survey (Platino study). A cluster sampling of subjects 40 years of age or older, representative of the metropolitan areas of 5 Latin American cities (Sao Paulo, Mexico, Montevideo, Santiago and Caracas) was chosen. Spirometry according to ATS standards was done before and after inhalation of 200 micrograms of salbutamol in 5183 subjects. Prevalences of airflow obstruction were estimated using different criteria, in tests done before and after bronchodilator use, and with reference values for pre- or post-bronchodilator use. Bronchodilator testing reduced the overall prevalence of FEV(1)/FVC% < 0.70 from 21.7% to 14% (35%). In the group with FEV(1)/FVC < 0.70 after bronchodilator use, 21% were asymptomatic from the respiratory point of view, and lacked significant adverse exposures. Subjects below the 5th percentile for FEV(1)/FVC and FEV(1)/FEV(6) were fewer than those with FEV(1)/FVC < 0.70, especially among the elderly. More subjects are below the 5th percentile of FEV(1)/FVC and FEV(1)/FEV(6) using reference values for tests after bronchodilator use than using the reference values determined without bronchodilator testing. Testing after bronchodilator use reduces the prevalence of airflow obstruction from 32 to 39% depending on the definition used. In addition, the subjects who were still obstructed after bronchodilator use were the ones who showed more respiratory symptoms and exposure to tobacco and other smokes and dusts, than subjects with reversible obstruction, suggesting an increased specificity for COPD.

Diagnostic labeling of COPD in five Latin American cities.

BACKGROUND: COPD is a major worldwide problem with a rising prevalence. Despite its importance, there is a lack of information regarding underdiagnosis and misdiagnosis of COPD in different countries. As part of the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar study, we examined the relationship between prior diagnostic label and airway obstruction in the metropolitan areas of five Latin American cities (São Paulo, Santiago, Mexico City, Montevideo, and Caracas). METHODS: A two-stage sampling strategy was used in each of the five areas to obtain probability samples of adults aged >or= 40 years. Participants completed a questionnaire that included questions on prior diagnoses, and prebronchodilator and postbronchodilator spirometry. A study diagnosis of COPD was based on airway obstruction, defined as a postbronchodilator FEV(1)/FVC < 0.70. RESULTS: Valid spirometry and prior diagnosis information was obtained for 5,303 participants; 758 subjects had a study diagnosis of COPD, of which 672 cases (88.7%) had not been previously diagnosed. The prevalence of undiagnosed COPD was 12.7%, ranging from 6.9% in Mexico City to 18.2% in Montevideo. Among 237 subjects with a prior COPD diagnosis, only 86 subjects (36.3%) had postbronchodilator FEV(1)/FVC < 0.7, while 151 subjects (63.7%) had normal spirometric values. In the same group of 237 subjects, only 34% reported ever undergoing spirometry prior to our study. CONCLUSIONS: Inaccurate diagnostic labeling of COPD represents an important health problem in Latin America. One possible explanation is the low rate of spirometry for COPD diagnosis.

The long-term stability of portable spirometers used in a multinational study of the prevalence of chronic obstructive pulmonary disease.

BACKGROUND: We report the performance of an ultrasound-based portable spirometer (EasyOne) used in a population-based survey of the prevalence of chronic obstructive pulmonary disease, conducted in 5 Latin American cities: São Paulo, Brazil; México City, México; Montevideo, Uruguay; Santiago, Chile; and Caracas, Venezuela (the Latin American COPD Prevalence Study [PLATINO]). METHODS: During the survey period (which ranged from 3 months to 6 months in the various locations) we collected daily calibration data from the 70 EasyOne spirometers used in the 5 survey cities. The calibrations were conducted with a 3-L syringe, and the calibration data were stored in the spirometer's database. RESULTS: Ninety-seven percent of the calibration volumes were within +/- 64 mL (2.1%) of the 3-L calibration signal. Excluding data from the first city studied (São Paulo), where one calibration syringe had to be replaced, 98% of the calibration checks were within +/- 50 mL (1.7%). The measured volume was affected only minimally by the syringe's peak flow or emptying time. CONCLUSION: In these 70 EasyOne spirometers neither calibration nor linearity changed during the study. Such calibration stability is a valuable feature in spirometry surveys and in the clinical setting.