Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD

Background Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced. Objective To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD. Methods Eleven patients with COPD (676 8 years; forced expiratory volume in 1s (FEV1)456 8%ref) and 10 healthy controls (666 4 years; FEV1 906 7% ref) cycled 45 min above LT (65% peak oxygen uptake (V9O2 peak)and another 7 patients (656 6 years; FEV1 506 4%ref)and 7 controls (566 9 years;FEV1 926 6%ref) cycled 45 min below their LT (50% V9O2 peak). Biopsies from the vastus lateralis muscle were obtained before exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression of the peroxisome proliferator-activated receptor- g coactivator-1 a (PGC-1a)mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V9O2. Results Skeletal muscle mtDNA/nDNA fell significantly after exercise above the LT both in controls and in patients with COPD, but the changes were greater in those with COPD. These changes correlated with production of reactive oxygen species, increases in manganese superoxide dismutase and PGC-1 a mRNA and returned to baseline values 1 week later. This pattern of response wa was also observed, albeit minimised, in patients exercising below the LT. Conclusions In patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1 a mRNA seen in healthy subjects probably due to oxidative stress.

Granulomatous Reaction to Pneumocystis jirovecii Diagnosed in a Bronchoalveolar Lavage: A Case Report.

BACKGROUND: Granulomatous reaction to Pneumocystis jirovecii is a rare but well-known pathological finding encountered in the setting of immunosuppression, HIV infection being the most common cause. It can also potentially complicate the treatment of hematological malignancies, typically when drugs lowering the count and function of lymphocytes are used. Lung biopsy is considered the gold standard for the diagnosis of granulomatous P. jirovecii pneumonia, whereas the diffuse alveolar form is usually detected cytologically in bronchoalveolar lavage (BAL). CASE: A female patient pursuing R-CHOP chemotherapy for the treatment of multiple hematological malignancies developed a rapidly progressing dyspnea. Chest CT scans revealed a worsening of a known infiltrative lung disease thought to be secondary to her chemotherapy. Alterations compatible with a drug-induced interstitial lung disease and well-formed focally necrotizing granulomas were observed on an open lung biopsy, but no microorganism was identified with special stains. Eventually, a granulomatous reaction to P. jirovecii was found in a BAL and allowed appropriate treatment with rapid improvement of the dyspnea. CONCLUSION: Because granulomas are tissue-bound structures, they are rarely described in BAL. This article describes the first reported cytological diagnosis of a granulomatous reaction to P. jirovecii and the potential diagnostic interest of such a peculiar finding.

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.

Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies.

Focal pleural thickening mimicking pleural plaques on chest computed tomography: tips and tricks.

Diagnosis of pleural plaques (PPs) is commonly straightforward, especially when a typical appearance is observed in a context of previous asbestos exposure. Nevertheless, numerous causes of focal pleural thickening may be seen in routine practice. They may be related to normal structures, functional pleural thickening, previous tuberculosis, pleural metastasis, silicosis or other rarer conditions. An application of a rigorous technical approach as well as a familiarity with loco-regional anatomy and the knowledge of typical aspects of PP are required. Indeed, false-positive or false-negative results may engender psychological and medico-legal consequences or can delay diagnosis of malignant pleural involvement. Correct recognition of PPs is crucial, as they may also be an independent risk factor for mortality from lung cancer in asbestos-exposed workers particularly in either smokers or former/ex-smokers. Finally, the presence of PP(s) may help in considering asbestosis as a cause of interstitial lung disease predominating in the subpleural area of the lower lobes. The aim of this pictorial essay is to provide a brief reminder of the normal anatomy of the pleura and its surroundings as well as the various aspects of PPs. Afterwards, the common pitfalls encountered in PP diagnosis will be emphasized and practical clues to differentiate actual plaque and pseudoplaque will be concisely described.

High-resolution computed tomography and histopathological findings in hypersensitivity pneumonitis: a pictorial essay

Abstract Hypersensitivity pneumonitis is a diffuse interstitial and granulomatous lung disease caused by the inhalation of any one of a number of antigens. The objective of this study was to illustrate the spectrum of abnormalities in high-resolution computed tomography and histopathological findings related to hypersensitivity pneumonitis. We retrospectively evaluated patients who had been diagnosed with hypersensitivity pneumonitis (on the basis of clinical-radiological or clinical-radiological-pathological correlations) and had undergone lung biopsy. Hypersensitivity pneumonitis is clinically divided into acute, subacute, and chronic forms; high-resolution computed tomography findings correlate with the time of exposure; and the two occasionally overlap. In the subacute form, centrilobular micronodules, ground-glass opacities, and air trapping are characteristic high-resolution computed tomography findings, whereas histopathology shows lymphocytic inflammatory infiltrates, bronchiolitis, variable degrees of organizing pneumonia, and giant cells. In the chronic form, high-resolution computed tomography shows traction bronchiectasis, honeycombing, and lung fibrosis, the last also being seen in the biopsy sample. A definitive diagnosis of hypersensitivity pneumonitis can be made only through a multidisciplinary approach, by correlating clinical findings, exposure history, high-resolution computed tomography findings, and lung biopsy findings.

Multimorbidity patterns in a national representative sample of the Spanish adult population.

BACKGROUND: In the context of population aging, multimorbidity has emerged as a growing concern in public health. However, little is known about multimorbidity patterns and other issues surrounding chronic diseases. The aim of our study was to examine multimorbidity patterns, the relationship between physical and mental conditions and the distribution of multimorbidity in the Spanish adult population. METHODS: Data from this cross-sectional study was collected from the COURAGE study. A total of 4,583 participants from Spain were included, 3,625 aged over 50. An exploratory factor analysis was conducted to detect multimorbidity patterns in the population over 50 years of age. Crude and adjusted binary logistic regressions were performed to identify individual associations between physical and mental conditions. RESULTS: THREE MULTIMORBIDITY PATTERNS ROSE: 'cardio-respiratory' (angina, asthma, chronic lung disease), 'mental-arthritis' (arthritis, depression, anxiety) and the 'aggregated pattern' (angina, hypertension, stroke, diabetes, cataracts, edentulism, arthritis). After adjusting for covariates, asthma, chronic lung disease, arthritis and the number of physical conditions were associated with depression. Angina and the number of physical conditions were associated with a higher risk of anxiety. With regard to multimorbidity distribution, women over 65 years suffered from the highest rate of multimorbidity (67.3%). CONCLUSION: Multimorbidity prevalence occurs in a high percentage of the Spanish population, especially in the elderly. There are specific multimorbidity patterns and individual associations between physical and mental conditions, which bring new insights into the complexity of chronic patients. There is need to implement patient-centered care which involves these interactions rather than merely paying attention to individual diseases.

Surgically-treated Hip Fracture in older People. With Special Emphasis on Mortality Analysis

Hip fractures are associated with significant morbidity and mortality. Cervical and trochanteric fractures have a different morphometry, surgical treatment, and outcome. Polypharmacy, common in older people, is associated with increased mortality. The risk factors for mortality can be identified based on cause-of-death analysis. In this population-based study, 461 older, surgically in 1999-2000 treated hip fracture patients were enrolled. Incidence, morphometry, medication, mortality, and cause-of-death were analysed. Hip fractures were most commonly sustained by women, occurred mostly indoors, and often in institutions. One in four patients had sustained a previous fracture. Routine clinical radiographs revealed no differences in the hip geometry between hip fracture types. Age-adjusted mortality was higher in men than in women during the follow-up. Chronic lung disease and male sex were predictors of mortality after cervical fracture. In men, potent anticholinergics were associated with excess age-adjusted mortality. Men were more likely to die from circulatory disease and dementia after hip fracture than women. Mortality after hip fracture was 3-fold higher than that of the general population, including every cause-of-death class. Fracture prevention in institutions and homes, indoor safety measures, and treatment of chronic lung diseases should be encouraged. Hip morphometry analyses require more accurate measures than that provided by routine radiographs. Careful use of potent anticholinergics may reduce mortality. Compared to the general population, excess mortality after hip fracture was evident up to 9 years after hip fracture. Cause-of-death analysis indicates that all major comorbidities require optimal treatment after hip fracture surgery.

Does cotinine act upon reactive oxygen species and peroxidases?

Nicotine, an oxidizing agent, is certainly one of the most widely used alkaloids in the world. It is, together with its main metabolite, cotinine, responsible for tobacco-dependence. The use of tobacco is closely associated with lung disease, morphological leukocyte modification and generation of oxidant species. The aim of this study was to look for a possible relationship between cotinine, oxidant species generation and oxidative processes. After studying the action of cotinine in some chemical oxidation models and on the enzymatic kinetics of peroxidases (myeloperoxidase and horseradish peroxidase), we concluded that cotinine does not act directly upon H2O2, HOCl, taurine chloramines, horseradish peroxidase or myeloperoxidase.

Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia). The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD) and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS). The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8), patients that presented COPD and died of its complications or associated diseases (N = 7), and patients that died of ARDS (N = 7). Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells) was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001), and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS), 0.44 (controls) (P<0.001), and 0.36 (COPD). These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue.

Cardiopulmonary exercise testing variables as predictors of long-term outcome in thoracic sarcoidosis

Cardiopulmonary exercise testing (CPET) plays an important role in the assessment of functional capacity in patients with interstitial lung disease. The aim of this study was to identify CPET measures that might be helpful in predicting the vital capacity and diffusion capacity outcomes of patients with thoracic sarcoidosis. A longitudinal study was conducted on 42 nonsmoking patients with thoracic sarcoidosis (median age = 46.5 years, 22 females). At the first evaluation, spirometry, the measurement of single-breath carbon monoxide diffusing capacity (D LCOsb) and CPET were performed. Five years later, the patients underwent a second evaluation consisting of spirometry and D LCOsb measurement. After 5 years, forced vital capacity (FVC)% and D LCOsb% had decreased significantly [95.5 (82-105) vs 87.5 (58-103) and 93.5 (79-103) vs 84.5 (44-102), respectively; P < 0.0001 for both]. In CPET, the peak oxygen uptake, maximum respiratory rate, breathing reserve, alveolar-arterial oxygen pressure gradient at peak exercise (P(A-a)O2), and Δ SpO2 values showed a strong correlation with the relative differences for FVC% and D LCOsb% (P < 0.0001 for all). P(A-a)O2 ≥22 mmHg and breathing reserve ≤40% were identified as significant independent variables for the decline in pulmonary function. Patients with thoracic sarcoidosis showed a significant reduction in FVC% and D LCOsb% after 5 years of follow-up. These data show that the outcome measures of CPET are predictors of the decline of pulmonary function.

Perceptions de personnes vivant avec une MPOC sévère au regard de leur fin de vie

Vivre avec une maladie pulmonaire obstructive chronique (MPOC), c’est vivre avec une maladie chronique, dégénérative et irréversible. La dyspnée qui l’accompagne demande une adaptation continuelle à de multiples incapacités. La qualité de vie des personnes vivant avec la MPOC s’en trouve compromise. Au Québec, le taux de mortalité de la MPOC a doublé depuis 20 ans. Si plusieurs études se sont intéressées à la symptomatologie vécue dans la dernière année de vie, aucune n’a abordé spécifiquement les perceptions de personnes vivant avec une MPOC sévère au regard de leur fin de vie. La présente étude avait justement pour but de décrire ces perceptions dans la perspective de la théorie de l’humain en devenir. Cette étude qualitative descriptive fut réalisée auprès de six personnes dans un centre hospitalier universitaire de la région de Montréal. L’analyse des entrevues a été réalisée selon la méthode de Miles et Huberman (2003) à partir de la transcription intégrale des entrevues. Cette analyse a permis de dégager quatre thèmes qui reflètent les perceptions des participants au regard de leur fin de vie, soit: 1) vivre et se voir décliner, 2) vivre et se préparer à mourir, 3) mourir d’une MPOC c’est étouffer et 4) mourir entouré à l’hôpital. Cette étude a mis en évidence que les personnes vivant avec une MPOC sévère souhaitent mourir à l’hôpital entouré de leurs proches. Cette étude contribue à une connaissance plus globale de l’expérience de fin de vie. De plus, elle propose des recommandations pour la recherche, la pratique, la formation et la gestion infirmière.

Développement d’un instrument d’évaluation des besoins de réadaptation des personnes atteintes de maladies respiratoires chroniques

La réadaptation pulmonaire est une intervention dont l’efficacité est largement reconnue. Cette efficacité a été établie grâce à l’utilisation d’instruments de mesure d’impact global. Les patients bénéficiant des programmes de réadaptation pulmonaire possèdent des caractéristiques variées et souffrent généralement de maladie pulmonaire obstructive chronique à différents degrés. En fonction de leurs différents besoins, les patients répondent de façon variable aux composantes d’un programme de réadaptation pulmonaire. Il est recommandé d’individualiser les programmes en fonction des besoins des patients afin d’en optimiser les effets. À cette fin, l’évaluation des besoins de réadaptation des patients est nécessaire. Comme il n’existe actuellement aucun instrument standardisé pour procéder à cette évaluation, nous avons entrepris d’en développer un à l’aide de méthodes qualitatives et quantitatives de recherche. Un modèle conceptuel d’évaluation des besoins de réadaptation des patients a été élaboré suite aux résultats tirés de groupes de discussion, de la consultation de dossiers médicaux et d’une recension des écrits. À partir de ce modèle, des items devant être sélectionnés de façon individualisée parmi cinq domaines (reconnaissance des besoins, connaissance, motivation, attentes et buts) ont été pré-testés. Les tendances générales concernant la validité des items contenus dans le prototype d’instrument ont été vérifiées lors d’une étude pilote auprès de 50 répondants en réadaptation. Les pistes d’investigation dégagées dans ce mémoire serviront aux études de validation plus approfondies dont devrait faire l’objet ce prototype d’instrument dans le futur.

La programmation régionale des services ambulatoires de Laval : une avenue dans la responsabilisation populationnelle des soins de santé

Face aux pressions continues que subissent les systèmes de santé, de nombreuses réformes sont perpétuellement en cours pour améliorer le processus de soins et par conséquent, offrir des soins de qualité et accroître le niveau de santé des populations. Les réformes que connaissent actuellement les systèmes de santé visent à optimiser l’impact des services sur la santé de la population en introduisant le concept de la responsabilité populationnelle. Par ailleurs, il existe de plus en plus un consensus sur la nécessité d’établir une relation directe et durable entre les prestataires et la population des territoires desservies pour être en mesure de tenir compte des contextes personnels et sociaux des patients et de leurs familles et pour assurer la continuité des soins dans le temps et d’un service à l’autre. Cette thèse porte sur la Programmation régionale de services ambulatoires (PRSA) de Laval. Elle analyse cette programmation comme une solution innovatrice dans la mise en œuvre de la responsabilisation populationnelle des soins. La stratégie de recherche combine à la fois une revue intégrative de la littérature qui vise à analyser le bien-fondé de la PRSA; une étude quasi-expérimentale pour examiner ses effets; et enfin, une recherche synthétique de cas pour comprendre l’évolution de la PRSA et analyser l’institutionnalisation du changement dans les organisations de la santé. Dans le premier article, nous nous sommes employés à analyser le bien fondé c’est-à-dire la plausibilité des mécanismes causaux présumés. La PRSA est un modèle d’intégration régionale basée sur une approche populationnelle. La stratégie de réseaux intégrés de soins et de case management combinée avec une approche populationnelle telle que mise de l’avant par le PRSA sont trois éléments essentiels en faveur d’une responsabilité populationnelle des soins. À l’aide d’une revue intégrative de la littérature, nous avons démontré qu’il s’agit d’une programmation capable de consolider une intégration régionale en mettant de l’avant une approche populationnelle permettant de bien cibler les besoins des populations du territoire à desservir. Le deuxième article examine les effets populationnels de la PRSA en termes de réduction de la durée moyenne de séjour et de l’augmentation de la rétention régionale. Une approche quasi expérimentale a été utilisée. En ce qui concerne la durée moyenne de séjour, on n’observe aucune diminution pour l’asthme ni pour la démence. Par contre, il est plausible que l’implantation de la PRSA ait permis une diminution de la durée moyenne de séjour pour les maladies coronariennes, les MPOC, l’embolie pulmonaire et le cancer du sein. Pour la rétention régionale, aucun effet n’a été observé pour les MPOC, l’embolie pulmonaire et la démence. Une augmentation de la rétention régionale a été observée pour les maladies coronariennes, l’asthme et le cancer du sein. Cette augmentation pourrait être attribuée à la PRSA. Dans le troisième article, nous avons examiné les facteurs susceptibles d’expliquer l’évolution de la PRSA. En partant du point de vue des responsables de la programmation de la PRSA et les gestionnaires actuels de la programmation de services de la région de Laval, nous avons tenté de mieux cerner les facteurs qui ont provoqué la suspension du déploiement de la PRSA. Les résultats indiquent que les changements fréquents dans les structures dirigeantes du réseau de la santé ainsi que l’interférence de plusieurs autres réformes ont été un obstacle dans le maintien de la PRSA. Dans le contexte actuel des réformes en santé où l’approche de réseaux intégrés de soins et de responsabilité populationnelle sont mises de l’avant, les résultats de cette thèse apportent un éclairage certain sur l’opérationnalisation de ces orientations.