Comorbidities of COPD Cavaillès, Arnaud; Brinchault-Rabin, Graziella; Dixmier, Adrien ...
European respiratory review
22, Issue:
130
Journal Article
Peer reviewed
Open access
By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common ...risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately.
Women and COPD: do we need more evidence? Gut-Gobert, Christophe; Cavaillès, Arnaud; Dixmier, Adrien ...
European respiratory review,
03/2019, Volume:
28, Issue:
151
Journal Article
Peer reviewed
Open access
The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and ...exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.
Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop ...rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4.
T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies.
In asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4.
T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.
Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular ...morphological features provide additional valuable information. The significance of the "immune alveolitis" cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients' characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD.
We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD.
Between January 2012 and December 2018, 249 patients were included. Mean age was 57 ± 16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively).
Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses.
Background:
Anastomotic complications are common after lung transplantation (1.4–33% of cases) and still associated with a high morbi-mortality.
Methods:
The current study is a monocenter ...retrospective analysis of symptomatic anastomotic complications (SAC) occurring after lung transplantation between 2010 and 2016, using the macroscopic, diameter, and suture (M-D-S) classification from consensus of French experts in bronchoscopy. The objectives were to determine incidence from surgery, risk factors, and impact of survival of SAC. We defined SAC as M-D-S abnormalities (stenosis ⩾ 50% or dehiscence) requiring bronchoscopic or surgical interventions.
Results:
A total of 121 patients were included. SAC occurred in 26.5% of patients (n = 32), divided in symptomatic stenosis for 23.7% (n = 29), and symptomatic dehiscence in 2.5% (n = 3). In multivariate analysis, donor bacterial lung infection HR 2.08 (1.04–4.17), p = 0.04 and age above 50 years HR 3.26 (1.04–10.26), p = 0.04 were associated with SAC occurrence. Cystic fibrosis etiology was associated with better survival on Kaplan–Meier curve (p < 0.001). SAC HR 2.15 (1.07–4.32), p = 0.03 was independently associated with worst survival. The 29 symptomatic patients because of stenosis required endoscopic procedure, of whom 16 patients needed bronchial stent placement. Four patients underwent surgery: three patients because of dehiscence and one because of severe bilateral stenosis (re-transplantation).
Discussion:
SAC occurred in 26.5% of patients. Donor lung infection was the only alterable identified factors. The increase rate of SAC in older patients above 50 years of age encourages in regular endoscopic monitoring.
Airway anastomotic complications remain a major cause of morbidity and mortality after lung transplantation (LT). Few data are available with regard to the use of silicone stents for these airway ...disorders. The aim of this retrospective study was to evaluate the clinical efficacy and safety of silicone stents for such an indication.
Data of adult lung transplant recipients who had procedures performed between January 1997 and December 2007 at our institution were reviewed retrospectively. We included patients with post-transplant airway complications who required bronchoscopic intervention with a silicone stent.
In 17 of 117 (14.5%) LT recipients, silicone stents were inserted at a mean time of 165 (range 5 to 360) days after surgery in order to palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all patients, and mean forced expiratory volume in 1 second (FEV(1)) increased by 672 +/- 496 ml (p < 0.001) after stent insertion. The stent-related complication rate was 0.13/patient per month. The latter consisted of obstructive granulomas (n = 10), mucus plugging (n = 7) and migration (n = 7), which were of mild to moderate severity and were successfully managed endoscopically. Mean stent duration was 266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of 23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in patients with and without airway complications (p = 0.36).
Silicone stents allow clinical and lung function improvement in patients with LT-related airway complications. Stent-related complications were of mild to moderate severity, and were appropriately managed endoscopically. Permanent resolution of airway stenosis was obtained in most patients, allowing definitive stent removal without recurrence.
Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing ...asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characteristic of asthma. The second, caused by either viral infection, allergens, pollutants or a combination of these, results in an acute Th1 and Th2 inflammation precipitating symptoms. In both, innate and adaptive immunities are involved, providing a series of potential targets for therapy. Molecules associated to the first, chronic inflammation constitute targets for preventing therapies, when these related to the second, acute signal provide the rationale for curative treatments. Toll like receptors and bronchial epithelial cell-derived cytokines, engaged upstream of inflammation constitute interesting candidates for future treatments. The great heterogeneity of asthma has to be taken into account when considering targets for therapy to identify clusters of responders and nonresponders, and an integrative system biology approach will be necessary to go further.
There is no unequivocal definition of exacerbation in asthma. These are defined as episodes of increased or aggravated respiratory symptoms or as use of oral corticosteroid therapy. Viral infection ...is the most frequent cause of exacerbations. Inflammation during exacerbations is heterogeneous. It may be associated with bronchial hypereosinophilia, which is used as a predictive marker for exacerbation, and with neutrophilia, which is more resistant to corticosteroids. During viral infection, an inappropriate Th1 antiviral inflammation develops, associated with the intrinsic Th2 activity that leads to an aberrant immune response. Exacerbations secondary to allergen exposure are classically described as due to a Th2-type inflammation; but Th1 response also seems to play a role. Exposure to air pollutants appears able not only to induce bronchial inflammation but also to potentiate the inflammatory reactions of patients with exacerbations.
To characterise patients with chronic obstructive pulmonary disease (COPD) who are rehospitalised for an acute exacerbation, to estimate the cost of these hospitalisations, to characterise high risk ...patient sub groups and to identify factors potentially associated with the risk of rehospitalisation.
This was a retrospective study using the French National Hospital Discharge Database. All patients aged ≥40 years hospitalised for an acute exacerbation of COPD between 2015 and 2016 were identified and followed for six months. Patients with at least one rehospitalisation for acute exacerbation of COPD constituted the rehospitalisation analysis population. A machine learning model was built to study the factors associated with the risk of rehospitalisation using decision tree analysis. A direct cost analysis was performed from the perspective of national health insurance.
A total of 143,006 eligible patients were hospitalised for an acute exacerbation of COPD (AECOPD) in 2015-2016 (mean age: 74 years; 62.1% men). 25,090 (18.8%) were rehospitalised for another exacerbation within six months. In this study, 8.5% of patients died during or immediately following the index hospitalisation and 10.5% died during or immediately after rehospitalisation (
<0.001). The specific cost of these rehospitalisations was € 5304. The overall total cost per patient of all AECOPD-related stays was € 9623, being significantly higher in patients who were rehospitalised (€ 16,275) compared to those who were not (€ 8208). In decision tree analysis, the most important driver of rehospitalisation was hospitalisation in the previous two years (contributing 85% of the information).
Rehospitalisations for acute exacerbations of COPD carry a high epidemiological and economic burden. Since hospitalisation for an acute exacerbation is the most important determinant of future rehospitalisations, management of COPD needs to focus on interventions aimed at decreasing the rehospitalisation risk of in order to lower the burden of disease.
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