Prevalence and management of chronic breathlessness in COPD in a tertiary care center.

BACKGROUND: Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. METHODS: A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. RESULTS: Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. CONCLUSION: Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.

Asthma-COPD overlap syndrome (ACOS) vs 'pure' COPD: a distinct phenotype?

BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients.

A competitive enzyme-linked immunosorbent assay for quantification of tetrastatin in body fluids and tumor extracts.

Basement membrane collagens or derived fragments are measured in biological fluids such as blood and urine of patients and appear to be useful for diagnosis, prognostication, or treatment monitoring as proposed for endostatin, a fragment of collagen XVIII, or tumstatin, a fragment of collagen IV. Tetrastatin, the NC1 alpha 4 collagen IV domain, was previously reported to inhibit tumor growth and angiogenesis. The aim of this study was to develop and validate a method to measure tetrastatin concentrations in human fluids. We developed a competitive enzyme-linked immunosorbent assay (ELISA). It allowed measuring tetrastatin levels in human serum, bronchial aspiration and bronchoalveolar lavage fluids, and lung tissue extracts. The tetrastatin level was significantly higher in tumor tissues than in healthy lung tissues. Tetrastatin competitive ELISA could be useful to quantify tetrastatin in tissues and biological fluids for the diagnosis or prognostication of diseases in which basement membrane metabolism may be altered, especially tumor progression.

Work-related respiratory symptoms in Champagne vineyard workers.

BACKGROUND: Vineyard workers (VW) are exposed to various respiratory allergens. The aims of the study were to determine the prevalence of work related respiratory symptoms (WRS) in Champagne VW in France and to analyze the relationships between symptoms, occupational exposure and sensitization profile. METHODS: VW of Reims area were prospectively recruited between 2007 and 2010. Demographic and occupational characteristics were recorded. Respiratory symptoms were scored for each month of the past year. Results of respiratory functional tests and skin prick tests for common respiratory allergens, grape moulds and vine pollen were recorded. RESULTS: 307 subjects were included. The prevalence of WRS was 11%. Compared to subjects with symptoms unrelated to work, subjects with WRS were more frequently sensitized to gramineae (34% vs 18%, p = 0.05), described ocular itching (74% vs 37%, p < 0.001) and seasonal symptoms (88% vs 69%, p = 0.03) mainly during lifting and trellising (57% vs 17%, p < 0.001). CONCLUSION: WRS are frequent in Champagne WV and are associated with a sensitization to gramineae and with activities performed close to vine in late spring.

[Take-home messages from the 2nd COPD 2023 Biennial of the French Society of Respiratory Diseases. Placing the patient at the center of the care pathway]. / Principaux messages de la deuxième Biennale BPCO 2023 de la SPLF. Le patient au cœur du parcours de soins.

INTRODUCTION: The second COPD Biennial organized by the COPD working group of the French Society of Respiratory Diseases took place in Paris (Cochin) on 13th December 2023. STATE OF THE ART: Major trends in 2023 were discussed; they encompassed concepts, definitions, biologics, care pathways, pulmonary rehabilitation and complex situations entailed by respiratory infections, cardiovascular comorbidities and pulmonary hypertension, and modalities of oxygen therapy and ventilation. PERSPECTIVES: The different talks underlined major changes in COPD including the concepts of pre-COPD, etiotypes, health trajectories and new definitions of exacerbation. Recent results in biologics for COPD open the door to new pharmacological options. Assessment of current care pathways in France highlighted some causes for concern. For example, pulmonary rehabilitation is a key but insufficiently practiced element. Respiratory infections require careful assessment and treatments. Diagnosis and treatment of cardiovascular comorbidities and pulmonary hypertension are of paramount importance. As of late, oxygen therapy and ventilation modalities have evolved, and are beginning to afford more personalized options. CONCLUSIONS: As regards COPD, a personalized approach is crucial, placing the patient at the center of the care pathway and facilitating coordination between healthcare providers.

[Bronchoscopic COPD treatments]. / Traitements endoscopiques de la BPCO.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with disabling respiratory symptoms including dyspnea, frequent exacerbations and chronic bronchitis. The currently available pharmacological and non-pharmacological therapies have limited efficacy, necessitating the development of interventional strategies, many of them endoscopic. STATE OF THE ART: Endoscopic lung volume reduction has markedly increased over recent years, principally as regards the endobronchial valves currently used in routine care. Indeed, multiple randomized trials have demonstrated a significant clinical benefit in a selected population identifiable due to the absence of interlobar collateral ventilation. Other endoscopic volume reduction techniques (polymers, thermal vapor, spirals) shall require additional studies before being considered as options in routine care. Targeted lung denervation (TLD) has aroused interest as a means of reducing exacerbations in the early phases of relevant studies. Endobronchial techniques (bronchoscopic cryospray, bronchial rheoplasty) are still at a very early stage of development, which is aimed at reducing the symptoms of chronic bronchitis. OUTLOOK: Aside from endobronchial valves, which are currently employed in routine care, all the above-mentioned endoscopic techniques require additional studies in order to determine their benefit/risk balance and to identify the population that would benefit the most. CONCLUSIONS: Endoscopic treatments constitute a major avenue of research and innovation in the therapeutic management of COPD. Inclusion of patients in disease registries and clinical trials remains essential, the objective being to gauge the interest of these treatments and their future role in everyday COPD management.

Dyspnea assessment in myotonic dystrophy type 1.

In myotonic mystrophy type 1 (DM1), combining respiratory symptom screening and respiratory function testing, is crucial to identify the appropriate time for ventilatory support initiation. Dyspnea has been little investigated in DM1. To provide a multidimensional description of dyspnea, questionnaires assessing dyspnea were administered to 34 consecutive adult patients with DM1 (median (25th-75th centile) age of 36 (28-49), Vital Capacity (VC) of 74 (64-87)% of predicted value). Dyspnea scores were low whatever the questionnaire used: Multidimensional Dyspnea Profile score of 2(0-4.7)/50 for dyspnea sensory descriptor and of 0 (0-4.7)/60 for the emotional descriptor, Visual Analogue Scale score of 0 (0-0)/10 in sitting and supine position and Borg score after six-minute walk test (6MWT) of 2.2 (1.8-4.2)/10. Eleven patients (32%) reported disabling dyspnea in daily living (modified Medical Research Council (mMRC) score ≥ 2). In comparison with patients with mMRC score < 2, patients with mMRC score ≥ 2 had a more severe motor handicap (Muscular Impairment Rating score of 4.0 (4.0-4.0) vs 3.0 (2.0-3.5), p<0.01), a lower 6MWT distance (373 (260-424) vs 436 (346-499)m, p = 0.03) and a lower VC (64 (48-74)% vs 75 (69-89)%, p = 0.02). These data suggest that the mMRC scale might be an easy-to-use and useful tool to assess dyspnea in daily living in DM1 patients. However, the interest of integrating the mMRC dyspnea scale in clinical practice to guide therapeutic management of DM1 patients remains to be assessed in further studies.

[Take-home messages from the COPD 2021 biennial of the French Society of Respiratory Diseases. Understanding to so as to better innovate]. / Principaux messages de la première Biennale BPCO 2021 de la SPLF. Mieux comprendre pour innover.

INTRODUCTION: The first COPD biennial organized by the French Society of Respiratory Diseases (SPLF) took place on 17 December 2021. STATE OF THE ART: The objective of the biennial was to discuss current knowledge regarding COPD pathophysiology, current treatments, research development, and future therapeutic approaches. PERSPECTIVES: The different lecturers laid emphasis on the complexity of pathophysiologic mechanisms including bronchial, bronchiolar and parenchymal alterations, and also dwelt on the role of microbiota composition in COPD pathenogenesis. They pointed out that addition to inhaled treatments, ventilatory support and endoscopic approaches have been increasingly optimized. The development of new therapeutic pathways such as biotherapy and cell therapy (stem cells…) call for further exploration. CONCLUSIONS: The dynamism of COPD research was repeatedly underlined, and needs to be further reinforced, the objective being to "understand so as to better innovate" so as to develop effective new strategies for treatment and management of COPD.

[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

[Treatment of GERD in asthma]. / Traitement du reflux gastro-œsophagien dans l'asthme.

Gastro-oesophageal reflux disease (GORD) is one of the most frequent conditions associated with asthma. GORD has an impact on asthma control and quality of life of asthmatic patients. Its treatment relies on lifestyle modifications, anti-acidic treatment with proton pump inhibitors (PPI) and/or surgical management by fundoplication in some situations. The impact of lifestyle modifications has not been analysed on asthma outcomes alone. Several randomised controlled trials assessed the efficacy of PPI on asthma control, peak expiratory flow and/or quality of life. The impact of fundoplication in asthma has mainly been analysed in retrospective or prospective observational studies. This review highlights the limited impact of GORD treatment on asthma control. Current guidelines are to restrict GORD treatment in asthma to asthmatic patients with actual symptomatic GORD. Given the lack of controlled studies, the place of surgical management of GORD in asthma is currently not defined.

[Obesity and asthma: Mechanisms and therapeutic options]. / Asthme et obésité : mécanismes et pistes thérapeutiques.

Asthma and obesity are both common conditions, which lead to a substantial public health burden. The obese-asthma phenotype is characterized by poor asthma control, impaired lung function and decreased efficacy of inhaled treatment. However, this phenotype is highly heterogeneous and involves numerous mechanisms, including systemic inflammation and adipokines. A role for microbiota modifications and genetics has been suggested. Obese-asthma patient management currently consists in weight loss and usual anti-asthmatic treatment. New therapeutic options are being evaluated.

Elastin expression in very severe human COPD.

Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2-3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2-3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.

[Alveolar hemorrhage associated with sarcoidosis]. / Sarcoïdose médiastinopulmonaire associée à une hémorragie intra-alvéolaire.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease of unknown origin. We report an unusual case associated with alveolar haemorrhage. CASE REPORT: An 18-year-old caucasian man was admitted for recent dyspnea. He reported regular tobacco- and occasional cannabis smoking. Lung CT scan revealed mediastinal lymphadenopathy and lung nodules in both fields. Bronchoalveolar lavage recovered bloody alveolar fluid containing many siderophages. Because of rapid deterioration leading to acute respiratory failure, intravenous corticosteroid treatment was started. Improvement was obtained in few days and a diagnosis of sarcoidosis was established based on lymph node biopsy performed under mediastinoscopy. CONCLUSION: This unusual case and those reported in the literature give us the opportunity to describe the characteristics of alveolar haemorrhage associated with sarcoidosis.

[Pulmonary artery stump thrombosis following pneumonectomy]. / Thrombose in situ du moignon artériel pulmonaire après pneumonectomie.

INTRODUCTION: Pulmonary artery stump thrombosis has been reported after pneumonectomy. The prevalence of risk factors for and outcome associated with this condition remain to be clearly evaluated. CASE REPORT: We describe three cases of pulmonary artery stump thrombosis occurring after pneumonectomy. No pulmonary embolism was observed despite the absence of anticoagulation therapy. The prevalence of arterial stump thrombosis after pneumonectomy has been estimated as 12%. It is often detected by CT scanning performed systematically as part of the routine follow up of lung cancer. Thrombus was identified as a filling defect with concave or convex margins, located at the bottom of the stump. DISCUSSION: Only one case of pulmonary embolism associated with pulmonary artery stump thrombosis has been described. The absence of complications associated with thrombus in this site suggests that anticoagulant therapy is not likely to be of benefit.

[Follicular bronchiolitis]. / Bronchiolite folliculaire.

INTRODUCTION: Follicular bronchiolitis (FB) is a rare type of cellular bronchiolitis characterised by the presence of hyperplastic lymphoid follicles with reactive germinal centres, distributed along the bronchovascular bundles. OBSERVATION: A non-smoking 36 year old woman was seen because of progressive exertional dyspnoea for 2 years. Chest x-ray and lung CT scan were normal. Pulmonary function tests revealed irreversible airflow obstruction. Exercise testing showed a ventilatory limitation of aerobic capacity with limitation of volume recruitment. The diagnosis of FB was obtained by surgical biopsy. A deficiency of immunoglobulins G4 and M was found. CONCLUSION: The main clinical manifestation of FB is exertional dyspnoea in a young patient. The lung CT scan frequently shows peripheral micronodules but a normal scan does not exclude the diagnosis. The main causes of FB are collagen vascular diseases (especially rheumatoid arthritis) and immunodeficiency syndromes. The treatment of FB is not well defined.