Temporal variations of dyspnea, fatigue, and lung function in chronic lung disease

Background. Research investigating symptom management in patients with chronic obstructive pulmonary disease (COPD) largely has been undertaken assuming the homeostatic construct, without regard to potential roles of circadian rhythms. Temporal relations among dyspnea, fatigue, peak expiratory flow rate (PEFR) and objective measures of activity/rest have not been reported in COPD. ^ Objectives. The specific aims of this study were to (1) explore the 24-hour patterns of dyspnea, fatigue, and PEFR in subjects with COPD; (2) examine the relations among dyspnea, fatigue, and PEFR in COPD; and (3) examine the relations among objective measures of activity/rest and dyspnea, fatigue, and PEFR in COPD. ^ Methods. The repeated-measures design involved 10 subjects with COPD who self-assessed dyspnea and fatigue by 100 mm visual analog scales, and PEFR by peak flow meter in their home 5 times a day for 8 days. Activity/rest was measured by wrist actigraphy. Single and population mean cosinor analyses and correlations were computed for dyspnea, fatigue, and PEFR; correlations were done among these variables and activity/rest. ^ Results. Circadian rhythms were documented by single cosinor analysis in 40% of the subjects for dyspnea, 60% for fatigue, and 60% for PEFR. The population cosinor analysis of PEFR yielded a significant rhythm (p < .05). The 8-day 24-hour means of dyspnea and fatigue was moderately correlated (r = .48, p < .01). Dyspnea and PEFR, and fatigue and PEFR, were weakly correlated in a negative way (r = −.11, p < .05 and r = −.15, p < .01 respectively). Weak to moderate correlations (r = .12–.34, p < .05) were demonstrated between PEFR and mean activity level measured up to 4 hours before PEFR measurement. ^ Conclusions. The findings suggest that (1) the dyspnea and fatigue experienced by COPD patients are moderately related, (2) there is a weak to modest positive relation between PEFR and activity levels, and (3) temporal variation in lung function may not affect the dyspnea and fatigue experienced by patients with COPD. Further research, examining the relations among dyspnea, fatigue, PEFR, and activity/rest is needed. Replication of this study is suggested with a larger sample size. ^

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition ( Health ABC) study is a prospective observational cohort of well functioning individuals aged 70 - 79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease ( OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p< 0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p< 0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p< 0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 ( adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to -1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.

Prolonged effects of a home-based intervention in patients with chronic illness

Background: Data on the long-term benefits of nonspecific disease management programs are limited. We performed a long-term follow-up of a previously published randomized trial. Methods: We compared all-cause mortality and recurrent hospitalization during median follow-up of 7.5 years in a heterogeneous cohort of patients with chronic illness initially exposed to a multidisciplinary, homebased intervention (HBI) (n = 260) or to usual postdischarge care (n = 268). Results: During follow-up, HBI had no impact on all-cause mortality (relative risk, 1.04; 95% confidence interval, 0.80-1.35) or event-free survival from death or unplanned hospitalization (relative risk, 1.03; 95% confidence interval, 0.86-1.24). Initial analysis suggested that HBI had only a marginal impact in reducing unplanned hospitalization, with 677 readmissions vs 824 for the usual care group (mean +/- SD rate, 0.72 +/- 0.96 vs 0.84 +/- 1.20 readmissions/patient per year; P = .08). When accounting for increased hospital activity in HBI patients with chronic obstructive pulmonary disease during follow-up for 2 years, post hoc analyses showed that HBI reduced readmissions by 14% within 2 years in patients without this condition (mean +/- SD rate, 0.54 +/- 0.72 vs 0.63 +/- 0.88 readmission/patient per year; P =. 04) and by 21% in all surviving patients within 3 to 8 years (mean +/- SD rate, 0.64 +/- 1.26 vs 0.81 +/- 1.61 readmissions/ patient per year; P =. 03). Overall, recurrent hospital costs were significantly lower ( 14%) in the HBI group (mean +/- SD, $ 823 +/- $ 1642 vs $ 960 +/- $ 1376 per patient per year; P =. 045). Conclusion: This unique study suggests that a nonspecific HBI provides long-term cost benefits in a range of chronic illnesses, except for chronic obstructive pulmonary disease.

Validity of the portable piko-6 spirometer used for screening obstructive airway diseases in community pharmacy practice

Background: Obstructive airway diseases (OADs) are among the leading causes of morbidity and mortality worldwide. Shortness of breath (SOB) is the main symptom associated with OADs. International guidelines from the Global Initiative for Chronic Lung Disease (GOLD) and the Global Initiative for Asthma (GINA) have recommended spirometry as an indispensable tool for the diagnosis of asthma and chronic obstructive pulmonary diseases (COPD), but spirometry is rarely used in family practice. Simple and reliable diagnostic tools are necessary for screening community patients with onset of OADs for timely management. Purpose: This thesis examined screening utility of the PiKo-6 forced expiratory volume in one second (pFEV₁) , in six second (pFEV₆), and the pRatio ( pFEV₁/pFEV₆) in SOB patients for OADs in community pharmacy settings. FEV₆ has recently been suggested an excellent surrogate for Forced Vital Capacity (FVC), which requires maximum exhalation of the lungs. Methods: Patients with SOB symptoms who were prescribed pulmonary inhalers, by their family physicians, were recruited via community pharmacies. Trained pharmacists collected two PiKo-6 tests to assess the repeatability of the PiKo-6 device. All patients performed laboratory spirometry ( FEV₁, FVC and FEV₁/FVC) to obtain physician diagnosis of their OADs. The results of the PiKo-6 spirometer and laboratory spirometer were compared. In addition, the PiKo-6 pRatio and laboratory FEV₁/FVC were assessed against physician diagnosed COPD. Results: Sixty three patients volunteered to perform the PiKo-6 spirometry. Of these, 52.4 % were men (age 53.9 ± 15.3 years; BMI 31.9 ± 7.40 kg/m2). Repeated testing with pFEV₁, pFEV6 and pRatio correlated significantly (within correlation, r = 0.835, p-Value≤ 0.05 ; 0.872, p- Value≤ 0.05; and 0.664, p-Value≤ 0.05). In addition, pFEV₁, pFEV6 and pRatio correlated significantly with FEV₁, FVC and FEV₁/FVC, respectively (between correlation = 0.630, p- Value≤ 0.05 ; 0.660, p-Value≤ 0.05 and 0.580, p-Value≤ 0.05). The cut-off value corresponding to the greatest sum of sensitivity and specificity of pRatio for physician-diagnosed COPD was <0.80, the sensitivity and specificity were 84 % and 50%, respectively. Conclusions The portable PiKo-6 correlates moderately well with the standard spirometry, when delivered by community pharmacists to patients with OADs. The PiKo-6 spirometer may play a role in screening patients suspected of having an OAD in community pharmacies that may benefit from early physician diagnosis and appropriate management.

Altération de la régénération musculaire dans la maladie pulmonaire obstructive chronique

Altération de la régénération musculaire dans la maladie pulmonaire obstructive chronique. La maladie pulmonaire obstructive chronique (MPOC) est caractérisée par une obstruction bronchique irréversible et progressive. L’atrophie musculaire périphérique y est fréquente et a un impact négatif sur la capacité fonctionnelle et la survie des sujets atteints. Toutefois, on ignore si une altération du processus de régénération musculaire est un processus ayant cours dans l’atrophie musculaire périphérique. Le but de la présente thèse était donc d’étudier les cellules satellites, principales cellules responsables de la régénération musculaire dans les muscles périphériques de patients ayant une MPOC. Dans un premier temps, nous avons évalué l’historique de réplication du tissu musculaire et la sénescence des cellules satellites. Les changements morphologiques ayant lieu dans le muscle au cours de la progression de la maladie rendent le muscle plus susceptible aux dommages, induisant un raccourcissement prématuré des télomères. Un raccourcissement des télomères chez les sujets ayant une MPOC avec atrophie est concomitant avec une augmentation du nombre de cellules satellites sénescentes et de l’épuisement du potentiel de régénération compromettant le maintien de la masse musculaire chez ces sujets. Dans un deuxième et troisième temps, nous avons étudié les étapes amenant une cellule satellite vers une cellule musculaire dans les muscles périphériques et respiratoires de patients ayant une MPOC comparativement à des sujets contrôles. Les cellules satellites sont impliquées dans la réparation du tissu musculaire. Dans les cellules satellites provenant des sujets ayant une MPOC, une altération de la prolifération et de la différentiation a été observée. Ces résultats sont compatibles avec une altération de la régénération musculaire pouvant conduire à l’atrophie musculaire dans la MPOC. Le quatrième volet de ce projet s’intéressait à l’impact d’un entraînement en résistance sur l’activité des cellules satellites et le rôle joué par la myostatine dans ce contexte. La littérature montre que l’exercice en résistance est bien toléré et aide les patients ayant une MPOC à retrouver une meilleure qualité de vie. Cependant, il semble qu’ils n’y répondent pas tous aussi bien que les sujets contrôles. La capacité de réponse des cellules satellites à un entraînement en résistance semble inadéquate, suggérant ainsi un défaut de leur activation. Dans la dernière étude de cette thèse, nous avons voulu évaluer l’impact de l’inflammation systémique en étudiant SAA1, une protéine de phase aiguë et p21, une protéine du cycle cellulaire dans la dégradation des protéines des cellules musculaires. Les liens de causalité entre l’affection primaire et les différentes comorbidités demeurent nébuleux dans la MPOC. SAA1 et p21 sont augmentés dans les muscles squelettiques des patients ayant une MPOC et par ailleurs, SAA1 est capable d’induire la dégradation des protéines musculaires. Cette thèse expose les premiers éléments impliquant l’altération de la régénération musculaire avec la dysfonction musculaire observée chez les patients ayant une MPOC. Ces résultats vont certainement contribuer au développement de nouvelles thérapies et stratégies d’intervention dans le but d’améliorer la qualité de vie des personnes atteintes d’une MPOC. En somme, les travaux effectués dans le cadre de la présente thèse montrent que plusieurs mécanismes agissent de concert avec l’inactivité physique afin d’induire le phénotype dysfonctionnel dans les muscles des patients ayant une MPOC.

Caractérisation du syndrome de chevauchement de l’asthme et de la maladie pulmonaire obstructive chronique

Maladies fréquentes, l’asthme touche 8,4% de la population canadienne âgée de 12 ans et plus et la maladie pulmonaire obstructive chronique (MPOC) touche de 5 à 15% de la population âgée entre 35 et 79 ans. L’asthme et la MPOC peuvent coexister chez un patient. Ce phénomène appelé syndrome de chevauchement de l’asthme et de la MPOC (ACOS) toucherait environ 10% à 55% des patients MPOC. Afin de mieux caractériser l’ACOS et les effets indésirables des médicaments utilisés pour traiter la MPOC, deux études ont été mises en place. Une première étude réalisée auprès de pneumologues a permis de décrire les méthodes de diagnostic, de traitement et d’évaluation de la maitrise de l’ACOS dans la pratique clinique. Les pneumologues rapportent que le diagnostic devrait être basé sur les caractéristiques cliniques, les tests de fonction pulmonaire et l'intuition clinique du médecin. De plus, un corticostéroïde inhalé en combinaison et un bronchodilatateur inhalé à longue durée d’action devraient être introduits rapidement dans le plan de traitement. La deuxième étude a permis d’évaluer la fréquence des effets indésirables chez les patients MPOC/ACOS traités avec un bronchodilatateur inhalé à longue durée d’action. Cette étude démontre que les effets indésirables sont fréquents chez les patients MPOC/ACOS et que la sécheresse buccale et la gorge sèche sont les plus rapportés. Ces résultats démontrent que la mise en place de lignes directrices pour l’ACOS ainsi qu’une meilleure connaissance du profil de tolérance des bronchodilatateurs inhalés à longue durée d’action seraient bénéfiques pour les patients

Caractérisation du syndrome de chevauchement de l’asthme et de la maladie pulmonaire obstructive chronique

Maladies fréquentes, l’asthme touche 8,4% de la population canadienne âgée de 12 ans et plus et la maladie pulmonaire obstructive chronique (MPOC) touche de 5 à 15% de la population âgée entre 35 et 79 ans. L’asthme et la MPOC peuvent coexister chez un patient. Ce phénomène appelé syndrome de chevauchement de l’asthme et de la MPOC (ACOS) toucherait environ 10% à 55% des patients MPOC. Afin de mieux caractériser l’ACOS et les effets indésirables des médicaments utilisés pour traiter la MPOC, deux études ont été mises en place. Une première étude réalisée auprès de pneumologues a permis de décrire les méthodes de diagnostic, de traitement et d’évaluation de la maitrise de l’ACOS dans la pratique clinique. Les pneumologues rapportent que le diagnostic devrait être basé sur les caractéristiques cliniques, les tests de fonction pulmonaire et l'intuition clinique du médecin. De plus, un corticostéroïde inhalé en combinaison et un bronchodilatateur inhalé à longue durée d’action devraient être introduits rapidement dans le plan de traitement. La deuxième étude a permis d’évaluer la fréquence des effets indésirables chez les patients MPOC/ACOS traités avec un bronchodilatateur inhalé à longue durée d’action. Cette étude démontre que les effets indésirables sont fréquents chez les patients MPOC/ACOS et que la sécheresse buccale et la gorge sèche sont les plus rapportés. Ces résultats démontrent que la mise en place de lignes directrices pour l’ACOS ainsi qu’une meilleure connaissance du profil de tolérance des bronchodilatateurs inhalés à longue durée d’action seraient bénéfiques pour les patients

Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle

Chronic sustained hypoxia (CH) induces structural and functional adaptations in respiratory muscles of animal models, however the underlying molecular mechanisms are unclear. This study explores the putative role of CH-induced redox remodeling in a translational mouse model, with a focus on the sternohyoid—a representative upper airway dilator muscle involved in the control of pharyngeal airway caliber. We hypothesized that exposure to CH induces redox disturbance in mouse sternohyoid muscle in a time-dependent manner affecting metabolic capacity and contractile performance. C57Bl6/J mice were exposed to normoxia or normobaric CH (FiO2 = 0.1) for 1, 3, or 6 weeks. A second cohort of animals was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine in the drinking water). Following CH exposure, we performed 2D redox proteomics with mass spectrometry, metabolic enzyme activity assays, and cell-signaling assays. Additionally, we assessed isotonic contractile and endurance properties ex vivo. Temporal changes in protein oxidation and glycolytic enzyme activities were observed. Redox modulation of sternohyoid muscle proteins key to contraction, metabolism and cellular homeostasis was identified. There was no change in redox-sensitive proteasome activity or HIF-1α content, but CH decreased phospho-JNK content independent of antioxidant supplementation. CH was detrimental to sternohyoid force- and power-generating capacity and this was prevented by chronic antioxidant supplementation. We conclude that CH causes upper airway dilator muscle dysfunction due to redox modulation of proteins key to function and homeostasis. Such changes could serve to further disrupt respiratory homeostasis in diseases characterized by CH such as chronic obstructive pulmonary disease. Antioxidants may have potential use as an adjunctive therapy in hypoxic respiratory disease.

Implantation Of Transcatheter Aortic Valve Prosthesis Through The Ascending Aorta Concomitant With Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass.

Introdution: The transcatheter aortic valve implantation in the treatment of high-risk symptomatic aortic stenosis has increased the number of implants every year. The learning curve for transcatheter aortic valve implantation has improved since the last 12 years, allowing access alternatives. The aim of this study is to approach the implantation of transcatheter aortic valve through transaortic via associated with off-pump cardiopulmonary bypass surgery in a 67-year-old man, with chronic obstructive pulmonary disease, arterial hypertension and kidney transplant. Off-pump coronary artery bypass surgery was performed and the valve in the aortic position was released successfully. There were no complications in the intraoperative and postoperative period. Gradient reduction, effective orifice increasing of the prosthesis and absence of valvular regurgitation after implantation were observed by transesophageal echocardiography. Procedural success demonstrates that implantation of transcatheter aortic valve through the ascending aorta associated with coronary artery bypass surgery without CPB is a new option for these patients.

Tratamento farmacológico da DPOC

Aproximadamente sete milhões de brasileiros acima de 40 anos são acometidos pela DPOC. Nos últimos anos, importantes avanços foram registrados no campo do tratamento medicamentoso dessa condição. Foi realizada uma revisão sistemática incluindo artigos originais sobre tratamento farmacológico da DPOC publicados entre 2005 e 2009, indexados em bases de dados nacionais e internacionais e escritos em inglês, espanhol ou português. Artigos com tamanho amostral menor de 100 indivíduos foram excluídos. Os desfechos sintomas, função pulmonar, qualidade de vida, exacerbações, mortalidade e efeitos adversos foram pesquisados. Os artigos foram classificados segundo o critério da Global Initiative for Chronic Obstructive Lung Disease para nível de evidência científica (grau de recomendação A, B e C). Dos 84 artigos selecionados, 40 (47,6%), 18 (21,4%) e 26 (31,0%) foram classificados com graus A, B e C, respectivamente. Das 420 análises oriundas desses artigos, 236 referiam-se à comparação de fármacos contra placebo nos diversos desfechos estudados. Dessas 236 análises, os fármacos mais frequentemente estudados foram anticolinérgicos de longa duração, a combinação β2-agonistas de longa duração + corticosteroides inalatórios e corticosteroides inalatórios isolados em 66, 48 e 42 análises, respectivamente. Nas mesmas análises, os desfechos função pulmonar, efeitos adversos e sintomas geraram 58, 54 e 35 análises, respectivamente. A maioria dos estudos mostrou que os medicamentos aliviaram os sintomas, melhoraram a qualidade de vida, a função pulmonar e preveniram as exacerbações. Poucos estudos contemplaram o desfecho mortalidade, e o papel do tratamento medicamentoso nesse desfecho ainda não está completamente definido. Os fármacos estudados são seguros no manejo da DPOC, com poucos efeitos adversos.

Doença pulmonar obstrutiva crônica e fatores associados em São Paulo, SP, 2008-2009

OBJETIVO: Estimar a prevalência e fatores associados à doença pulmonar obstrutiva crônica. MÉTODOS: Estudo transversal, de base populacional com 1.441 indivíduos de ambos os sexos e com 40 anos de idade ou mais no município de São Paulo, SP, entre 2008 e 2009. As informações foram coletadas por meio de entrevistas domiciliares e os participantes foram selecionados a partir de amostragem probabilística, estratificada por sexo e idade, e por conglomerados em dois estágios (setores censitários e domicílios). Foi realizada regressão múltipla de Poisson na análise ajustada. RESULTADOS: Dos entrevistados, 4,2% (IC95% 3,1;5,4) referiram doença pulmonar obstrutiva crônica. Após análise ajustada, identificaram-se os seguintes fatores independentemente associados ao agravo: número de cigarros fumados na vida (> 1.500/nenhum) RP = 3,85 (IC95%: 1,87;7,94), cansar-se com facilidade (sim/não) RP = 2,61 (IC95% 1,39;4,90), idade (60 a 69 anos/50 a 59 anos) RP = 3,27 (IC95% 1,01;11,24), idade (70 anos e mais/50 a 59 anos) RP = 4,29 (IC95% 1,30;14,29), problemas de saúde nos últimos 15 dias (sim/não) RP = 1,31 (IC95% 1,02;1,77), e atividade física no tempo livre (sim/não) RP = 0,57 (IC95% 0,26;0,97). CONCLUSÕES: A prevalência da doença pulmonar obstrutiva crônica é elevada e está associada ao uso do tabaco e idade acima de 60 anos. Os problemas de saúde freqüentes e redução da atividade física no tempo livre podem ser considerados conseqüências dessa doença.

Perfil de pacientes que evoluem para óbito por tuberculose no município de São Paulo, 2002

OBJETIVO: Descrever o perfil de pacientes adultos residentes no município de São Paulo que evoluíram para óbito associado à tuberculose, segundo fatores biológicos, ambientais e institucionais. MÉTODOS: Estudo descritivo, abrangendo todos os óbitos por tuberculose (N=416) ocorridos em 2002, entre maiores de 15 anos. Os dados analisados foram obtidos do Sistema Municipal de Informações de Mortalidade, prontuários hospitalares, Serviço de Verificação de Óbitos e Sistema de Vigilância de Tuberculose. Os cálculos dos riscos relativos e intervalos de confiança de 95 por cento (IC 95 por cento) tiveram como referência o sexo feminino, grupo de 15 a 29 anos, e os naturais do Estado de São Paulo. A análise comparativa usou o teste do qui-quadrado de Pearson e o exato de Fisher para variáveis categóricas e o teste Kruskal-Wallis para variáveis contínuas. RESULTADOS: Do total de óbitos, 78 por cento apresentavam a forma pulmonar; o diagnóstico foi efetuado após a morte em 30 por cento e em unidades de atendimento primário em 14 por cento dos casos; 44 por cento não iniciaram tratamento; 49 por cento não foram notificados; 76 por cento eram homens e a mediana da idade foi de 51 anos; 52 por cento tinham até quatro anos de estudo, 4 por cento eram prováveis moradores de rua. As taxas de mortalidade aumentavam com a idade, sendo de 5,0/100.000 no município, variando de zero a 35, conforme o distrito. Para 82 de 232 pacientes com registro de tratamento, havia referência de tratamento anterior, e desses, 41 o haviam abandonado. Constatou-se presença de diabetes (16 por cento), doença pulmonar obstrutiva crônica (19 por cento), HIV (11 por cento), tabagismo (71 por cento) e alcoolismo (64 por cento) nos pacientes. CONCLUSÕES: Homens acima de 50 anos, migrantes e residentes em distritos com baixo Índice de Desenvolvimento Humano apresentam maiores riscos de óbito. )A pouca escolaridade e apresentar co-morbidades são características importante Observou-se baixa participação das unidades básicas de saúde no diagnóstico e a elevada sub-notificação

Diagnosis, Assessment, and Treatment of Non-Pulmonary Arterial Hypertension Pulmonary Hypertension

The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary hypertension (PH). The term ""non-PAH PH"" summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH. (J Am Coll Cardiol 2009;54:S85-96) (C) 2009 by the American College of Cardiology Foundation

Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson`s correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. (C) 2009 Elsevier Ltd. All rights reserved.