Dolores Moreno

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.

Sex-related differences in COPD in five Latin American cities: the PLATINO study

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40–1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56– -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.

Chronic obstructive pulmonary disease and body mass index in five Latin America cities: The PLATINO study

BACKGROUND The body mass index (BMI) is a prognostic factor for chronic obstructive pulmonary disease (COPD). Despite its importance, little information is available regarding BMI alteration in COPD from a population-based study. We examined characteristics by BMI categories in the total and COPD populations in five Latin-American cities, and explored the factors influencing BMI in COPD. METHODS COPD was defined as a postbronchodilator forced expiratory volume in the first second/forced vital capacity (FEV(1)/FVC) <0.70. BMI was categorized as underweight (< 20 kg/m(2)), normal weight (20-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (> or = 30.0 kg/m(2)). RESULTS Interviews were completed in 5571 subjects from 6711 eligible individuals, and spirometry was performed in 5314 subjects. There were 759 subjects with COPD and 4555 without COPD. Compared with the non-COPD group, there was a higher proportion of COPD subjects in the underweight and normal weight categories, and a lower proportion in the obese category. Over one-half COPD subjects had BMI over 25 kg/m(2). No differences in BMI strata among countries were found in COPD subjects. Factors associated with lower BMI in males with COPD were aging, current smoking, and global initiative for chronic obstructive lung disease (GOLD) stages III-IV, whereas wheeze and residing in Santiago and Montevideo were associated with higher BMI. In females with COPD, current smoking, lower education, and GOLD stages II-IV were associated with lower BMI, while dyspnea and wheeze were associated with higher BMI. CONCLUSIONS BMI alterations are common in COPD with no significant differences among countries. Current smoking, age, GOLD stages, education level, residing in Santiago and Montevideo, dyspnea and wheeze were independently associated with BMI in COPD.

Pharmacological properties of thalidomide and its analogues.

Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomide) and CC-4047 (Actimid, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukins (IL) 1-beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of alpha glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies.

Frequency of Self-Reported COPD Exacerbation and Airflow Obstruction in Five Latin American Cities: The Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (PLATINO) Study

BACKGROUND Recurrent exacerbations are common in COPD patients. Limited information exists regarding exacerbation frequency in COPD patients from epidemiologic studies. We examined the frequency of self-reported exacerbations and the factors influencing exacerbation frequency among COPD patients in a population-based study conducted in Latin America. METHODS We used a post-bronchodilator FEV(1)/FVC ratio of < 0.70 to define COPD. Exacerbation was self-reported and defined by symptoms (deterioration of breathing symptoms that affected usual daily activities or caused missed work). RESULTS Spirometry was performed in 5,314 subjects. There were 759 subjects with airflow limitation; of these, 18.2% reported ever having had an exacerbation, 7.9% reported having an exacerbation, and 6.2% reported having an exacerbation requiring at least a doctor visit within the past year. The proportion of individuals with an exacerbation significantly increased by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, from 4.2% in stage 1 to 28.9% in stages 3 and 4. The self-reported exacerbation rate was 0.58 exacerbations per year. The rate of exacerbations requiring at least a doctor visit and length of stay in hospital due to exacerbations also increased as COPD severity progressed. The factors associated with having an exacerbation in the past year were dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and disease severity of GOLD stages 3 and 4. CONCLUSIONS The proportion of individuals with airflow limitation and self-reported exacerbation increases as the disease severity progresses. Dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and more severe obstruction were significantly associated with having an exacerbation in the past year.

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

BACKGROUND Acute 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. METHODS COPD was defined by GOLD criteria (post-bronchodilator FEV(1)/FVC<0.70). In this analysis, subjects with pre-bronchodilator FEV(1)/FVC <0.70 but > or =0.70 post-bronchodilator were considered to have reversible obstruction. Bronchodilator responsiveness after albuterol 200microg was assessed using three definitions: a) FVC and/or FEV(1) increment > or =12% plus > or =200mL over baseline; b) FEV(1)> or =15% increase over baseline; and c) FEV(1) increase > or =10% of predicted value. RESULTS There 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. FEV(1) changes were lower (110.6+/-7.40 vs. 164.7+/-11.8mL) and FVC higher (146.5+/-14.2mL vs. -131.0+/-19.6mL) in COPD subjects compared with reversible obstructed. Substantial overlap in FEV(1) and FVC changes was observed among the groups. Acute bronchodilator responsiveness in COPD persons was associated with less obstruction and never smoking. CONCLUSIONS Over 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 FEV(1) and FVC changes after bronchodilator among the groups makes it difficult to determine a threshold for separating them.

Metabolic syndrome and asthma.

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients

BACKGROUND One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. METHODS Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. RESULTS Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. CONCLUSION The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

Surfactant Protein D in Chronic Obstructive Pulmonary Disease (COPD)

In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Disease (COPD) have been described. One of the important biomarkers is Surfactant Protein D (SPD) since serum SPD levels have been associated with lung function or health status in patients with severe COPD. Several interesting evidences of the protein and gene polymorphisms have been described. The present review highlights the current literature, recent patents and, future prospects of this important collection.

Smoke, Biomass Exposure, and COPD Risk in the Primary Care Setting: The PUMA Study

BACKGROUND: The evidence indicates that risk factors other than smoking are important in the development of COPD. It has been postulated that less traditional risk factors (eg, exposure to coal and/or biomass smoke) may interact with smoking to further increase COPD risk. This analysis evaluated the effect of exposure to biomass and smoking on COPD risk in a primary care setting in Latin America. METHODS: Subjects attending routine primary care visits, ≥40 y old, who were current or former smokers or were exposed to biomass smoke, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 and the lower limit of normal. Smoking was defined by pack-years (≤ 20, 20–30, or > 30), and biomass exposure was defined as an exposure to coal or wood (for heating, cooking, or both) for ≥ 10 y. RESULTS: One thousand seven hundred forty-three individuals completed the questionnaire, and 1,540 performed spirometry. Irrespective of COPD definition, approximately 40% of COPD subjects reported exposure to biomass versus 30% of those without COPD. A higher proportion of COPD subjects (post-bronchodilator FEV1/FVC < 0.70) than those without COPD smoked > 30 pack-years (66% vs 39%); similar results were found with the lower limit of normal definition. Analysis of exposure to biomass > 10 y plus smoking > 20 pack-years (reference was no exposure) found that tobacco smoking (crude odds ratio [OR] 4.50, 95% CI 2.73–7.41; adjusted OR 3.30, 95% CI 1.93–5.63) and biomass exposure (crude OR 3.66, 95% CI 2.00–6.73; adjusted OR 2.28, 95% CI 1.18–4.41) were risk factors for COPD, with smoking a possible confounder for the association between biomass and COPD (post-bronchodilator FEV1/FVC < 0.70); similar results were found with the lower limit of normal definition. CONCLUSIONS: Subjects with COPD from primary care had a higher exposure to biomass and smoking compared with non-COPD subjects. Smoking and biomass are both risk factors for COPD, but they do not appear to have an additive effect.