No / Context. The End of Life Care Strategy for England highlights effective communication between patients and professionals as key to facilitating patient involvement in advance care planning. The strategy emphasizes that, currently, communication in patients with noncancer life-limiting conditions is likely to be inadequate, and research has identified that patients with chronic obstructive pulmonary disease and heart failure have a poor understanding of their condition. Objectives. To identify existing interventions of patient-professional communication developed for life-limiting conditions and explore the applicability of interventions developed within a cancer framework to other diagnostic groups. Methods. A comprehensive literature review of studies describing communication interventions for patients receiving end-of-life care was undertaken. Ten electronic databases were searched. Inclusion criteria were all English language studies relating to patient-professional communication interventions for patients with life-limiting conditions receiving end-of-life care. Results. Of the 755 articles initially identified, 16 met the inclusion criteria. Three core themes emerged from the synthesis of the literature: using education to enhance professional communication skills, using communication to improve patient understanding, and using communication skills to facilitate advance care planning. Conclusion. Although limited, evidence relating to the development and evaluation of communication interventions for patients with life-limiting illnesses would suggest that a successful intervention should include combined components of training, patient discussion, and education. In a context of limited resources and an increasing number of patients living and dying with chronic life-limiting conditions, the need for appropriate and effective communication strategies should be seen as a priority for both research and policy.

Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death in the US, and idiopathic pulmonary fibrosis (IPF), a type of Interstitial Lung Disease (ILD), is a fast acting, irreversible disease that leads to mortality within 3-5 years. RNA-sequencing provides the opportunity to quantitatively examine the sequences of millions mRNAs, and offers the potential to gain unprecedented insights into the structure of chronic non-malignant lung disease transcriptome. By identifying changes in splicing and novel loci expression associated with disease, we may be able to gain a better understanding of their pathogenesis, identify novel disease-specific biomarkers, and find better targets for therapy. Using RNA-seq data that our group generated on 281 human lung tissue samples (47=Control, 131=COPD, 103=ILD), I initially defined the transcriptomic landscape of lung tissue by identifying which genes were expressed in each tissue sample. I used a mixture model to separate genes into reliable and not reliable expression. Next, I employed reads that overlapped splice junctions in a linear model interaction term to identify disease-specific differential splicing. I identified alternatively spliced genes between control and disease tissues and validated three (PDGFA, NUMB, SCEL) of these genes with qPCR and nanostring (a hybridization-based barcoding technique used to quantify transcripts). Finally, I implemented and improved a pipeline to perform transcriptome assembly using Cufflinks that led to the identification of 1,855 novel loci that did not overlap with UCSC, Vega, and Ensembl annotations. The loci were classified into potential coding and non-coding loci (191 and 1,664, respectively). Expression analysis revealed that there were 120 IPF-associated and 10 emphysema-associated differentially expressed (q < 0.01) novel loci. RNA-seq provides a high-resolution transcript-level view of the pulmonary transcriptome and its modification in lung disease. It has enabled a new understanding of the lung transcriptome structure because it measures not only the transcripts we know but also the ones we do not know. The approaches and improvements I have employed have identified these novel targets and make possible further downstream functional analysis that could identify better targets for therapy and lead to an even better understanding of chronic lung disease pathogenesis. / 2999-01-01T00:00:00Z

From a BPS perspective, COPD and other chronic diseases may have a significant negative impact on those living with them and may be associated with higher rates of depression and anxiety and lower levels of health-related quality of life (HRQOL). Certain factors, such as spirituality, may influence the negative impact of chronic disease on the relationship between mood and functional independence and HRQOL. Also, gender may influence the relationship between mood, spirituality, and HRQOL for men and women living with chronic diseases. The current study included 136 patients undergoing physical rehabilitation at an IRF. Anxiety, depression, spirituality, HRQOL, and functional independence were evaluated for all. Mediation models were tested to determine the impact of spirituality on the relationships between mood and HRQOL and functional independence, and moderation models were tested to evaluate the impact of gender on the relationships between mood, spirituality, functional independence, and HRQOL. The current study yielded some inconclusive results but did evidence that COPD patients in acute inpatient physical rehabilitation facilities (IRF) have higher levels of anxiety than patients without COPD and also revealed that men with COPD have better HRQOL than do women with COPD. Spirituality was found to partially mediate the relationship between depression and HRQOL in IRF patients with COPD, but gender did not appear to moderate the relationships between mood, spirituality, functional independence, or HRQOL in IRF patients. As few studies on IRF patients with chronic diseases exist, continuing to evaluate patients in IRFs is important to enhance our BPS understanding of chronic disease.

Asthma is a chronic disease of the airways and affects many people regardless of their age, gender, race and socioeconomic status. Since asthma is recognised as one of the major causes of morbidity and mortality in people and especially in South Africa, the prescribing patterns, prevalence and medication cost of asthma in South Africa are saliently important and need to be investigated. A non-experimental, quantitative retrospective drug utilisation review was conducted on medicine claims data of a pharmaceutical benefit management company in a section of the private health care sector of South Africa. The study period was divided into four annual time periods (1 January 2008 to 31 December 2008, 1 January 2009 to 31 December 2009, 1 January 2010 to 31 December 2010 and 1 January 2011 to 31 December 2011). The prescribing patterns and cost of asthma medication were investigated and stratified according to province, age and gender. Patients were included if the prescriptions which were provided by the health care practitioners matched the Chronic Disease List (CDL) of South Africa and the International Classification of Disease (ICD-10) coding for asthma and chronic obstructive pulmonary disease (COPD). Data analysis was conducted by means of the SAS 9.3® computer package. Asthma patients were divided according to different age groups (there were five different age groups for this study), gender and geographical areas of South Africa. The study indicated a steady increase in the prevalence of asthma patients from 0.82% (n = 7949) in 2008 to 1.18% (n = 15 423) in 2009 and reached a minimum of 0.79% (n = 8554) in 2011. Analysis of the prevalence regarding geographical areas in South Africa suggested that Gauteng had the highest number [n = 17 696, (0.85%)] of asthma patients throughout the study period, followed by KwaZulu Natal [n = 8 628, 1.16%)] and the Western Cape [(n = 8513, 0.97%) (p < 0.05)]. The prevalence of asthma in female patients [0.89% (n = 26 588)] was higher than in their male counterparts [0.79% (n = 19 244)] (p > 0.05). The results showed that asthma was not as common chronic disease in children. The total number of asthma patients younger than 7 years represented 0.64% (n = 2 909). It was found that patients over 65 years of age showed the highest prevalence of the five age groups [1.94% (n = 13 403) (p < 0.05)]. The average number of asthma prescriptions per patient per year was 8.28 (95% CI, 8.16- 8.40) and 5.15 (95% CI, 5.06-5.23) in 2008 and 2011, respectively. The number of asthma items per prescription varied from 1.55 (95% CI, 1.55-1.56) in 2008 to 1.40 (95% CI, 1.39- 1.40) in 2011. Medication from the MIMS® pharmacological group (anti-asthmatics and bronchodilators) was used to identify asthma medication. The top three asthma medication with the highest prevalence in the study period were the anti-inflammatory inhaler of fluticasone (n = 39 721) followed by the single item combination product of budesonide/ formoterol (n = 25 121) and salbutamol (n = 24 296). The influence of COPD on asthma treatment and the costimplication thereof were investigated. Medication from the MIMS® pharmacological group (anti-asthmatics and bronchodilators) was used to identify COPD medication. This study also showed that COPD had an influence in the economic burden of the South African asthma population. The cost of medication is responsible for the single largest direct cost involved in the economic burden of asthma. This study showed that asthma represented 0.88% of the direct medication cost in the study (excluding hospitalisation and indirect cost). The average cost per prescription and average cost per asthma item both increased throughout the study period. The prescribing patterns for the different medication used in the treatment of asthma were investigated and recommendations for further research in this field of study were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, characterized by progressive and largely irreversible airflow limitation due to alveolar destruction (emphysema), small airway narrowing, and chronic bronchitis. It is one of the leading causes of morbidity and mortality worldwide and in the UK, it may affect approximately 1.5 per cent of the population; and up to one in eight emergency admissions may be due to COPD,corresponding to over one million bed days, with some 24160 people in the UK dying as a result of COPD in 2005 (Burden of Lung Disease 2nd Edition,British Thoracic Society 2006). Most cases of COPD are triggered by chronic inhalation of cigarette smoke.However, some people do not suffer from COPD even if they smoke for many years. COPD cannot be cured, and patients usually live with poor life quality. Treatments include giving up smoking, medication and oxygen therapy. Genetic factors contribute to the development of COPD. In Northern Europe,Z-AT homozygotes (342Glu Lys) develop emphysema in their third or forth decade. One explanation is AT deficiency because they form inactive polymers. However, this cannot explain why bronchoalveolar lavage fluid (BALF) from Z-AT homozygotes with emphysema contains more neutrophils than BALF from individuals with emphysema and normal AT (M-AT). Inhaling pollutants which include smoking (cigarettes, pipes, cigars, etc.) and other fumes such as those found in many industrial work environments probably also plays a role in an individual’s development of COPD. Previously, it has been shown that the polymeric conformer of AT is present in BALF from Z-AT homozygotes and that it is a chemoattractant for neutrophils in vitro (Parmar JS, 2002). These findings have been confirmed by others (Mulgrew AT, 2004). However, it is unknown where the polymers form and if 4 they are chemotactic in vivo. My colleague Dr Carl Atkison† showed that polymers of Z 1-AT are present in the alveolar wall of Z-AT homozygotes with emphysema, which accounts for 20% of the total AT from lung homogenates.These Z-AT individuals also have an excess of neutrophils in the alveolar wall compared with M-AT homozygotes. Furthermore, neutrophils and polymeric AT co-localize in the alveolar wall (Mahadeva R, 2005). To investigate whether there was a direct relationship between polymers of Z-AT and the excess neutrophils, polymers of AT were instilled into the lungs of wild-type mice (Mahadeva R, 2005). This produced a significant increase in neutrophil influx into the lungs compared with instillation of the native protein.Examination of the time course demonstrated that the influx of neutrophils was closely linked to the presence of polymeric AT. The mechanism of neutrophil recruitment in this mouse model was subsequently shown to be a direct chemotactic effect rather than stimulation of IL-8 homologues or other CXC chemokines. Oxidized AT (Ox-AT) promotes release of human monocyte chemoattractant protein-1 (MCP-1) and IL-8 from human lung type epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells. Native, cleaved, polymeric AT and secretory leukoproteinase inhibitor (SLPI) and oxidized conformations of cleaved, polymeric AT and SLPI did not have any significant effect on MCP-1 and IL-8 secretion. These findings were supported by the fact that instillation of Ox-AT into murine lungs resulted in an increase in JE (mouse MCP-1) and increased macrophage numbers in the bronchoalveolar lavage fluid. The effect of Ox-AT was dependent on NF- B and activator protein-1 (AP-1)/JNK. These findings have important implications. They demonstrate that the oxidation of methionines in AT by oxidants released by cigarette smoke or inflammatory cells not only reduces the anti-elastase lung protection, but also converts AT into a proinflammatory stimulus. Ox-AT generated in the airway † My colleagues’ contributions are acknowledged in future text where appropriate by the following superscripts: (a) Dr Sam Alam, (b) Dr Jichun Wang, (c) Dr Carl Atkinson, (d) Dr Sabina Janciauskiene. 5 interacts directly with epithelial cells to release chemokines IL-8 and MCP-1,which in turn attracts macrophages and neutrophils into the airways. The release of oxidants by these inflammatory cells oxidizes AT, perpetuating the cycle, potentially contributing to the pathogenesis of COPD. Furthermore, this demonstrates that molecules such as oxidants, anti-proteinases, and chemokines, rather than acting independently, collectively interact to cause emphysema (Li Z, 2009). To investigate the molecular basis for the interaction between Z-AT and Ox-AT associated with cigarette smoking, female mice transgenic for normal (MAT)or Z-AT on CBA background were exposed to cigarette smoke (CS). Transgenic mice for Z-AT developed a significant increase in pulmonary polymers following acute CS exposure. Increased levels of neutrophils in CSZ lungs were tightly correlated with polymer concentrations. Oxidation of human plasma Z-AT by CS or -chlorosuccinimide greatly accelerated polymerization, which could be abrogated by antioxidants. The results showed that cigarette smoke accelerated polymerization of Z-AT by oxidative modification, which in so doing further reduced pulmonary defense and increased neutrophil influx into the lungs. These novel findings provided a molecular explanation for the striking observation of premature emphysema in ZZ homozygote smokers, and raised the prospect of anti-oxidant therapy in ZAT related COPD (Alam S, 2011).

Introduction. Les mécanismes physiopathologiques du remodelage vasculaire pulmonaire chez le patient BPCO sont encore mal élucidés. L'inflammation pourrait jouer un rôle déterminant.Objectifs. Déterminer le rôle de l'interleukine 6 (IL6) dans la physiopathologie de l'hypertension pulmonaire (HTP) associée à la BPCO.Méthodes. Nous avons étudié le lien entre l'IL6 et l'HTP sur une population de patients atteints de BPCO, l'effet de l'hypoxie sur le développement d'une HTP chez des souris IL6-/- et l'effet in vitro de l'IL6 sur les cellules endothéliales et les cellules musculaires lisses d'artère pulmonaire humaine.Résultats. Les patients BPCO avec HTP présentaient un taux plasmatique d'IL6 circulante plus élevé. Le génotype GG de l'IL6 était corrélé à un risque plus élevé de développer une HTP. L'IL6 est produite par tous les acteurs cellulaires impliqués dans la physiopathologie du remodelage vasculaire pulmonaire et en particulier la cellule musculaire lisse. Sa synthèse, ainsi que celle de ses récepteurs, est très nettement stimulée par l'hypoxie aigue et chronique. L'IL6 participe probablement à l'entretien de la dysfonction endothéliale, à la migration des cellules musculaires lisses et au recrutement des cellules inflammatoires. Les souris IL6-/- sont partiellement protégées de l'hypertension pulmonaire hypoxique et présentent un moindre recrutement pulmonaire de cellules inflammatoires induit par l'hypoxie. Le taux d'IL6 est corrélé à une longueur télomérique plus courte chez les patients BPCO, témoignant d'un processus de vieillissement biologique accéléré. L'HTP associée à la BPCO ou à l'hypoxie chronique pourrait résulter d'une accentuation du processus de sénescence des cellules vasculaires pulmonaires, favorisé par l'inflammation.Conclusion. L'inflammation et plus particulièrement l'IL6 semblent fortement impliquées dans la physiopathologie du remodelage vasculaire pulmonaire chez le patient BPCO. / Introduction. The pathophysiological mechanisms responsible for pulmonary vascular remodeling in COPD remain poorly understood. Inflammation may play a major role.Objectives. To study the role of interleukin-6 (IL6) in the pathophysiology of pulmonary hypertension associated with COPD.Methods. We studied the relationship between IL6 and PH in a population of patients with COPD, the effect of hypoxia on the development of PH in mice IL6-/- and the effect of IL-6 on endothelial cells and smooth muscle cells of human pulmonary artery in vitro.Results. COPD patients with PH were characaterised by a more pronounced hypoxia and higher plasma levels of circulating IL-6. The GG genotype of IL-6 also correlated with a higher risk of developing PH in these patients. Each of the different cellular elements that promote pulmonary vascular remodeling are known to produce IL-6, with smooth muscle cells known to be a particularly important source of this cytokine In addition, synthesis of IL-6 and its associated receptors is increased in response to acute and chronic hypoxia. It is likely that IL-6 contributes to endothelial dysfunction, the migration and, indirectly, proliferation of smooth muscle cells, and recruitment of inflammatory cells. Indeed, IL6-/- mice are partially protected from hypoxia-associated pulmonary hypertension and demonstrate attenuated hypoxia-induced lung recruitment of inflammatory cells. Levels of IL-6 also correlate with shorter telomere length in patients with COPD, indicating a process of accelerated biological aging. This suggests that pulmonary hypertension secondary to COPD or chronic hypoxia may be due to inflammation-associated acceleration of normal pulmonary vascular cell sénescence.Conclusion. Inflammation in general, and IL-6 in particular, appear to be strongly involved in the pathophysiology of pulmonary vascular remodeling in patients with COPD

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelinesare used to guide clinical practices for treating Chronic Obstructive Pulmonary Disease (COPD). GOLD focuses heavily on stable COPD patients, limiting its use fornon-stable COPD patients such as those with severe, acute exacerbations of COPD (AECOPD) that require hospitalization. Although AECOPD can be heterogeneous, it can lead to deterioration of health and early death. Electronic health records (EHRs) can be used to analyze patient data for understanding disease progression and generating guideline evidence for AECOPD patients. However, because of its structure and representation, retrieving, analyzing, and properly interpreting EHR data can be challenging, and existing tools do not provide granular analytic capabil-ities for this data.<div><br></div><div>This dissertation presents, develops, and implements a novel approach that systematically captures the effect of interventions during patient medical encounters, and hence may support evidence generation for clinical guidelines in a systematic and principled way. A conceptual framework that structures components, such as data storage, aggregation, extraction, and visualization, to support EHR data analytics for granular analysis is introduced. We develop a software framework in Python based on these components to create longitudinal representations of raw medical data extracted from the Medical Information Mart for Intensive Care (MIMIC-III) clinical database. The software framework consists of two tools: Patient Aggregated Care Events (PACE), a novel tool for constructing and visualizing entire medical histories of both individual patients and patient cohorts, and Mark SIM, a Markov Chain Monte Carlo modeling and simulation tool for predicting clinical outcomes through probabilistic analysis that captures granular temporal aspects of aggregated, clinicaldata.<br></div><div><br></div><div>We assess the efficacy of antibiotic treatment and the optimal time of initiationfor in-hospitalized AECOPD patients as an application to probabilistic modeling. We identify 697 AECOPD patients of which 26.0% were administered antibiotics. Our model simulations show a 50% decrease in mortality rate as the number of patients administered antibiotics increase, and an estimated 5.5% mortality rate when antibiotics are initially administrated after 48 hours vs 1.8% when antibiotics are initially administrated between 24 and 48 hours. Our findings suggest that there may be amortality benefit in initiation of antibiotics early in patients with acute respiratory failure in ICU patients with severe AECOPD.<br></div><div><br></div><div>Thus, we show that it is feasible to enhance representation of EHRs to aggregate patients’ entire medical histories with temporal trends and support complex clinical questions to drive clinical guidelines for COPD.<br></div>

O exercício aeróbio foi recentemente descrito como capaz de reduzir a função pulmonar e diminuir o risco de desenvolver DPOC entre fumantes ativos. A plausibilidade biológica da influência da atividade física sobre o declínio da função pulmonar está relacionada aos efeitos anti-inflamatórios efeitos da atividade física, que tem sido descritos em estudos experimentais. A hipótese é que haveria uma interação entre exercício aeróbio e o desenvolvimento da doença. A fim de explorar mais a fisiopatologia da DPOC induzida pela exposição à fumaça de cigarro e os efeitos do exercício no desenvolvimento do enfisema, utilizamos um modelo experimental de DPOC. C57Bl6 foram divididos em quatro grupos: Controle, Fumo, Exercício e Fumo/Exercício. Os animais dos grupos Fumo foram expostos à fumaça de cigarro por 30 minutos por dia, 5 dias por semana, durante 24 semanas. Os animais dos grupos Exercício foram treinados em intensidade moderada durante 60 minutos por dia, 5 dias por semana durante 24 semanas. Os resultados demonstraram que o treinamento físico aeróbio regular de intensidade moderada inibiu o desenvolvimento de enfisema, o aumento do total de células inflamatórias e a produção de espécies reativas de oxigênio no LBA, além do aumento na geração de óxido nítrico exalado, induzido pela exposição à fumaça do cigarro, e inibiu o aumento de 8-isoprostano e MCP1, além de aumentar a expressão da GPx, SODCuZn, TIMP1 e IL-10 por células inflamatórias na parede alveolar. O estudo também mostrou que o treinamento físico aeróbio foi capaz de inibir a diminuição da elastância pulmonar induzida pela exposição à fumaça de cigarro, mas não reduziu o aumento de colágeno no parênquima pulmonar. Estes resultados sugerem que o treinamento físico regular aeróbico de intensidade moderada pode desempenhar um papel importante durante a instalação da doença devido ao seu efeito antioxidante e antiinflamatório / Aerobic exercise was recently described as capable to reduce lung function decline and risk of developing COPD among active smokers. The biological plausibility of the influence of physical activity on the decline of lung function relies on the anti-inflammatory effects of physical activity, which have been described in experimental studies. We hypothesized there would be an interaction between aerobic exercise and development of disease. In order to further explore the physiopathology of COPD induced by exposure to cigarette smoke and the effects of exercise in development of emphysema, we used an experimental model of DPOC. C57Bl6 were divided in four groups: Control, Smoke, Exercise and Smoke/Exercise. Smoke groups were exposed to cigarette smoke for 30 minutes a day, 5 days a week, for 24 weeks. Exercise groups were trained at moderate intensity exercise for 60 minutes/day, 5 days/week for 24 weeks. The results demonstrated that regular aerobic physical training of moderate intensity inhibited alveolar distension, the increase of total inflammatory cells and production of reactive oxygen species in BAL and the increase in the generation of exhaled nitric oxide induced by exposure to cigarette smoke, and reduced the expression of 8-isoprostane and MCP1 and increased the expression of GPx, SODCuZn, TIMP1 and IL-10 by inflammatory cells in the alveolar wall. The study also showed that aerobic physical training was able to inhibit the decrease in lung elastance induced by exposure to cigarette smoke, but not the content in collagen fibers. These results suggest that regular aerobic physical training of moderate intensity may play an important role during the installation of disease due to its antioxidant and antiinflammatory effects

INTRODUÇÃO: Os pacientes com asma crônica podem compartilhar similaridades clínicas e fisiológicas com pacientes com doença pulmonar obstrutiva crônica, tal como reversibilidade parcial ao broncodilatador ou pouca obstrução persistente do fluxo expiratório. Entretanto, não existem estudos comparando a patologia destas duas doenças em pacientes com idade similares e mesma gravidade da doença. MÉTODOS: Nós comparamos as dimensões das grandes e pequenas vias aéreas de 12 pacientes adultos (média±erro padrão, 32±3 anos) e 15 pacientes idosos e pré-idosos idosos (65±1 ano) não tabagista que foram a óbito por asma fatal com 14 pacientes tabagistas crônicos que foram a óbito por DPOC grave (71± 1 ano) e 19 pacientes-controle (56±1 ano). Usando a coloração de Movat e H&E, e a técnica de análise de imagens, nós quantificamos a espessura da membrana basal (MB) (valores expressos em ?m) a área de glândula submucosa nas grandes vias aéreas. Nas grandes e pequenas vias aéreas quantificamos a área de camada interna, a área de músculo liso e a área de camada externa. As áreas foram normalizadas pelo perímetro da MB (?m/?m2). RESULTADOS: os pacientes asmáticos adultos apresentaram a MB, área de músculo liso e a área da camada externa nas grandes e pequenas vias aéreas mais espessas, quando comparadas com os controles com idade similar com DPOC grave. Nos pacientes idosos e pré-idosos com asma, houve uma sobreposição na espessura da MB e na área da glândula submucosa, enquanto que nas pequenas e grandes vias aéreas a área de músculo liso foi mais espessa quando comparados com os controles com idade similar com pacientes com DPOC grave. Os pacientes com DPOC apresentaram nas pequenas e grandes vias aéreas as áreas de músculo liso menor quando comparada aos controles com idade similar. Os asmáticos adultos apresentaram a área de músculo liso maior quando comparada aos asmáticos idosos. CONCLUSÃO: Nossos dados fornecem novas informações sobre as mudanças patológicas que podem nos ajudar a entender melhor as similaridades e diferenças patológicas no pacientes adultos e idosos com asma comparados ao DPOC / Background: In some patients with chronic asthma, clinical and physiological similarities with chronic obstructive pulmonary disease may co-exist, such as partial reversibility to bronchodilators despite persistent expiratory airflow obstruction. However, pathologic analyses comparing both diseases in patients of similar age and disease severity are scarce. Methods: We compared the large and small airway dimensions in 12 younger (mean±SD, age 32 yr±3 yr) and 15 older (65 yr±1 yr) non-smoking fatal asthmatics with 14 chronic smokers with severe, fatal COPD (71 yr±1 yr) and 19 control patients (56 yr±1 yr). Using H&E, Movat\'s pentachrome staining and image analysis, we quantified large airway basement membrane (BM) thickness (?m); submucosal gland area; and large and small airway inner wall, smooth muscle and outer wall areas. Areas were normalized by BM perimeter (?m2/?m). Results: Younger adult fatal asthmatics had thicker BM, smooth muscle, and outer wall areas in both small and large airways when compared to agematched controls and fatal COPD patients. In older asthmatics, there was an overlap in BM thickness and submucosal gland area, whereas both large and small airway smooth muscle areas were thicker compared to age-matched controls and fatal COPD patients. COPD patients had thinner large and small airway smooth muscle areas compared to age-matched controls. Younger asthmatics had thicker small airway smooth muscle area compared to older asthmatics. Conclusion: Our data provide novel pathological substrate changes that may help us better understand physiological similarities and differences in younger and older patients with asthma compared to COPD.

O objetivo desse estudo foi avaliar a relação da mobilidade diafragmática com a função pulmonar e a força muscular respiratória em indivíduos com DPOC, utilizando a mensuração ultra-sonográfica do deslocamento crânio-caudal do ramo esquerdo da veia porta. Foram estudados 54 pacientes portadores de DPOC com hiperinsuflação pulmonar e 20 sujeitos saudáveis. Os parâmetros avaliados foram: mobilidade diafragmática, função pulmonar e as pressões respiratórias máximas. Pacientes com DPOC apresentaram menor mobilidade do diafragma (36,46 ± 10,90 mm) quando comparados a indivíduos saudáveis (46,33 ± 9,47) (p = 0,001). Nos indivíduos portadores de DPOC foram verificadas uma forte correlação com os parâmetros da função pulmonar que quantificam o aprisionamento de ar (VR: r = -0,60; p < 0,001; VR/CPT: r = -0,72; p < 0,001), uma moderada correlação com a obstrução de vias aéreas (VEF1: r = 0,55, p < 0,001; resistência das vias aéreas: r = -0,32, p = 0,02) e uma fraca correlação com a hiperinsuflação pulmonar (CPT: r = -0,28, p = 0,04). Não foi observada relação entre a mobilidade do diafragma e a força muscular respiratória (PImax: r = -0,11 e p = 0,43; PEmax: r = 0,03 e p = 0,80). Nossos resultados sugerem que a redução da mobilidade do diafragma em pacientes com DPOC ocorre principalmente devido ao aprisionamento de ar, não sendo influenciada pela hiperinsuflação pulmonar ou pela força muscular respiratória. / The purpose of this study was to use ultrasound to measure the craniocaudal displacement of the left branch of the portal vein in order to evaluate the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. We studied 54 COPD patients with pulmonary hyperinflation, together with 20 healthy subjects. Pulmonary function, maximal respiratory pressures, and diaphragm mobility were evaluated. COPD patients presented less diaphragm mobility than did healthy individuals (36.46 +/- 10.90 mm vs. 46.33 +/- 9.47 mm, respectively) (p = 0.001). In COPD patients, we found that diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60; p < 0.001; RV/TLC: r = -0.76; p < 0.001), moderately with airway obstruction (FEV1: r = 0.55, p < 0.001; airway resistance: r = -0.32, p = 0.02), and weakly with pulmonary hyperinflation (TLC: r = -0.28, p = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11 and p = 0.43; maximal expiratory pressure: r = 0.03 and p = 0.80). The results of this study suggest that the reduction in diaphragm mobility in COPD patients occurs mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.