In the May 2017 issue of the European Respiratory Journal (ERJ), Johnson et al. 1 proposed the term “chronic breathlessness syndrome” to describe the clinical situation in which “breathlessness that ...persists despite optimal treatment of the underlying pathophysiology and results in disability for the patient”. The term “disability” in this definition corresponds to “physical limitations and/or a variety of adverse psychosocial, spiritual or other consequences”, which very closely matches the World Health Organization definition of the word 2. The relationship between breathlessness and disability was well captured in the foreword of a document published in 2013 by the Forum of International Respiratory Societies 3, which begins: “When we are healthy, we take our breathing for granted …. But when our lung health is impaired, nothing else but our breathing really matters”. This has become the “catch phrase” of the French lung health foundation (“Fondation du Souffle”, www.lesouffle.org). The explicit definition of “chronic breathlessness” as proposed by Johnson et al. 1 differs very little from the implicit definition of “refractory breathlessness”, the term previously used in many studies, and which was proposed as a distinct entity by some of the authors of a previously published ERJ article 4. Johnson et al. 1 submit that defining and naming this new syndrome will improve the visibility of a distressing and debilitating condition that is too often overlooked and neglected 5. They postulate that this enhanced visibility will result in improved care and organisation of care, stronger research 6, and greater empowerment for patients and their caregivers. The Editorial by Basoééééééééééêèôéééôéêèéééôèéèééééééééôôééôééééôôôéééééôéêèéééééôéôôéééôéêèéôôééééôğlu 7 published in the May 2017 issue of the ERJ throws new light on this notion of empowerment. Making a daring but fascinating parallel between untreated dyspnoea and torture, Basoééééééééééêèôéééôéêèéééôèéèééééééééôôééôééééôôôéééééôéêèéééééôéôôéééôéêèéôôééééôğğlu 7 reminds us how and why addressing dyspnoea in general (and probably “chronic breathlessness” in particular) is a fundamental issue not only from the point of view of medicine per se, but also from the point of view of human rights (on this, see also 8). He also makes a very convincing case for the importance of empowerment in the management of dyspnoea. Still in the same issue of the ERJ, Calverley 9 comments on the new syndrome and, like us, concurs with Johnson et al. 1 about the relevance of making breathlessness a foremost concern of every clinician.
Background: Pulmonary artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH)
in COPD patients. We hypothesized that the risk for PH in COPD is ...increased by an elevation in the proinflammatory cytokines
interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1β, as well as by specific genetic polymorphisms of
these cytokines.
Methods: We assessed cytokine plasma levels and the polymorphisms G(â174)C IL-6, C(â511)T IL-1β, and A(â2518)G MCP-1 in 148 COPD patients
(recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers.
Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic
conditions.
Results: Patients with PH (mean pulmonary artery pressure PAP, ⥠25 mm Hg) had lower Pa o 2 and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results
or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP ( r = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable.
In patients with the IL-6 GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds
ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger
RNA in cultured human PA-SMCs.
Conclusions: Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.
In recent years, several global and local guidelines, recommendations and proposals on chronic obstructive pulmonary disease (COPD) management have been published 1–14. They illustrate the great ...interest in this disease that, although no cure exists, is no longer considered untreatable. They also reflect its major and growing burden from both public health and individual perspectives. Finally, they parallel the increasing knowledge of its pathophysiology, clinical characteristics and natural history, as well as of treatment effects, with the goal of personalising care as much as possible. Here, we aim to present recent proposals of the French-Language Respiratory Society (Sociééééôééèéééééééêèééôéôééétééééôééèéééééééêèééôéôéééé de Pneumologie de Langue Francaise (SPLF)) and put them in perspective with the similarly recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) document, which represents a major revision of GOLD proposals. It is also crucial to take this opportunity to emphasise here that the story of a guideline does not end with its production: the implementation phase is even more important and truly never ends until the next guideline, resulting in an endless cycle.
Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat ...pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded.
Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the "gold standard" used to establish the diagnosis of PCD.
This "gold standard" excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the "gold standard", while the qualitative evaluation was discordant with the "gold standard" in 3/10 cases. Among the patients with an inconclusive "gold standard", the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients.
When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.
The COPD “frequent exacerbator” phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this ...phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations.
Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters.
Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations.
These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype.
Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung ...alterations or are independent complications of smoking remains unclear.
To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO).
Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).
Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO.
Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The serotonin transporter (5-HTT) is involved in the pulmonary artery smooth muscle hyperplasia that leads to pulmonary hypertension (PH). Because hypoxia and 5-HTT gene polymorphism control 5-HTT ...expression, we examined 5-HTT gene polymorphism and PH in hypoxemic patients with advanced chronic obstructive pulmonary disease (COPD).
In 103 patients with COPD recruited in France (n=67) and the UK (n=36), we determined 5-HTT gene polymorphism and pulmonary artery pressure (PAP) measured during right heart catheterization (France) or Doppler echocardiography (UK). Ninety-eight subjects from the 2 countries served as control subjects. The distribution of 5-HTT gene polymorphism did not differ between patients and control subjects. In patients carrying the LL genotype, which is associated with higher levels of 5-HTT expression in pulmonary artery smooth muscle cells than the LS and SS genotypes, PH was more severe than in LS or SS patients. Mean PAP values in patients from France with the LL, LS, and SS genotypes were 34+/-3, 23+/-1, and 22+/-2 mm Hg (mean+/-SEM), respectively (P<0.01). Corresponding systolic PAP values in the UK were 40+/-3, 28+/-3, and 24+/-3 mm Hg, respectively (P<0.01). Compared with control subjects, platelet 5-HTT protein was increased in COPD patients in proportion to the hypoxemia level, and strong 5-HTT immunostaining was observed in remodeled pulmonary arteries from COPD patients.
5-HTT gene polymorphism appears to determine the severity of PH in hypoxemic patients with COPD. Because PH is an important prognostic factor in this disease, recognition of patients at risk for PH should be helpful in managing COPD.
Highlights • Nocturia was associated with prevalent hypertension after adjustment. • This association exhibited a dose–response relationship for all age strata. • The strength of the association was ...enhanced for patients over 64 years. • Nocturia is a strong independent predictor of prevalent hypertension in obstructive sleep apnea (OSA).
Abstract Physicians treating patients with lower respiratory tract infections face numerous challenges and treatment decisions. For example, when treating a patient with acute exacerbations of ...chronic obstructive pulmonary disease (AECOPD), a physician must determine: (1) whether the patient should be hospitalised; (2) the cause of the exacerbation; (3) whether bacterial infection is present; and (4) which antibacterial agent should be used (if antibacterial treatment is required). In this article, the key challenges faced by physicians treating patients with AECOPD are described and illustrated using a case study. The impact of antibiotic resistance and other factors influencing a physician's treatment decisions are discussed, and current evidence and guidelines which should inform these decisions are reviewed.
Chronic obstructive pulmonary disease (COPD) is a main cause of death due to interplaying factors, including comorbidities that interfere with symptoms and response to therapy. It is now admitted ...that COPD management should be based on clinical symptoms and health status and should consider the heterogeneity of patients' phenotypes and treatable traits. This precision medicine approach involves a regular assessment of the patient's status and of the expected benefits and risks of therapy. The cornerstone of COPD pharmacological therapy is inhaled long-acting bronchodilation. In patients with persistent or worsened symptoms, factors likely to interfere with treatment efficacy include the patient's non-adherence to therapy, treatment preference, inhaler misuse and/or comorbidities, which should be systematically investigated before escalation is considered. Several comorbidities are known to impact symptoms, physical and social activity and lung function. The possible long-term side-effects of inhaled corticosteroids contrasting with their over-prescription in COPD patients justify the regular assessment of their benefits and risks, and de-escalation under close monitoring after a sufficient period of stability is to be considered. While commonly used in clinical trials, the relevance of routine blood eosinophil counts to guide therapy adjustment is not fully clear. Patients' characteristics, which define phenotypes and treatable traits and thus guide therapy, often change during life, forming the basis of the concept of clinical trajectory. The application of individual trajectory-based management of COPD in clinical practice therefore implies that the benefit:risk ratio is regularly reviewed according to the evolution of the patient's traits over time to allow optimised therapy adjustments.
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