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.

[Nurse practitioners as key actors in pulmonary rehabilitation for chronic obstructive pulmonary disease]. / L'infirmier en pratique avancée, un acteur-clé dans le développement de la réadaptation respiratoire chez le patient atteint de BPCO.

INTRODUCTION: While pulmonary rehabilitation is registered in the COPD management guidelines with a high level of evidence, it is not adequately performed in accordance with patients' needs. Advanced nurse practitioners (IPA, in French) provide expertise enabling improved access and enhanced implementation of rehabilitation programs. Based on foreign experience, the present study has been designed to propose avenues for the development of more effective practices in France. METHODS: Using Google Scholar and Pubmed databases, a search algorithm was used to identify international publications from 2003 to 2022 dealing with the role of nurse practitioners (IP, in French) in respiratory rehabilitation for COPD patients. RESULTS: Fourteen articles, mainly from English-speaking countries, were analysed. The involvement of nurse practitioners in pulmonary rehabilitation is very broad-based, their main missions being initial disease assessment, therapeutic education, improved professional sensitivity and patient follow-up at all stages of a rehabilitation program. CONCLUSION: Nurse practitioners have a major role in the implementation of pulmonary rehabilitation programs for COPD patients. Their involvement at different levels can improve access and success of programs over time.

[The role of cardiac magnetic resonance imaging in pulmonary arterial hypertension and chronic thrombo-embolic pulmonary hypertension]. / Place de l'IRM cardiaque dans l'hypertension artérielle pulmonaire et l'hypertension pulmonaire thrombo-embolique chronique.

INTRODUCTION: Cardiac MRI is increasingly used to assess and monitor pulmonary vascular disease. STATE OF THE ART: In pulmonary arterial hypertension, the role of cardiac MRI has become more clearly defined due to its proven capacity to assess the morphology and function not only of the heart, but also of pulmonary circulation. Complementarily to echocardiography, technological advances have rendered it possible for MRI to search and assess shunts. More generally, MRI provides prognostic information on the follow-up of patients undergoing treatment. In cases of chronic thromboembolic pulmonary hypertension, chest MRI locates lesions and assesses pulmonary microcirculation, thereby guiding therapeutic choice. It is also an important prognostic marker in diagnosis and follow-up of patients undergoing treatment. To ensure high-quality examination, it is essential that the patient having to carry out repeated apneas cooperate. PROSPECTS: Studies are ongoing in view of clarifying the role of cardiac MRI as compared to right cardiac catheterization in the follow-up of patients with pulmonary arterial hypertension. CONCLUSIONS: Cardiac MRI is the examination of choice in assessment of right ventricular morphology and function. It is a minimally invasive technique with good inter- and intra-operator reproducibility in the evaluation of patients with pulmonary arterial hypertension and chronic pulmonary thromboembolic hypertension.

[Specific effect of exercise training on depression in COPD patients]. / Impact spécifique du réentraînement à l'exercice sur les symptômes de dépression dans la broncho-pneumopathie chronique obstructive : expérience du Réseau insuffisance respiratoire de Lorraine.

INTRODUCTION: Depression is a common comorbidity in COPD patients, worsening their quality of life and their current level of physical activity. Respiratory rehabilitation is therefore highly recommended for COPD patients but only few of them have access to that kind of program. In real life, exercise training is often the only therapeutic activity provided to patients. METHODS: The aim of this study was to evaluate the specific effect of exercise training on the level of depression (using Beck Depression inventory short form (BDI-SF)) and quality of life in COPD patients [using the Saint George's Respiratory Questionnaire (SGRQ)]. Five hundred and fifteen COPD patients were enrolled in home-based exercise training programs. 421 programs were completed and the data was available for 182 patients (SGRQ, BDI-SF et TE) at T0 and T12. RESULTS: Dyspnoea (mMRC), SGRQ, BDI-SF scores and TE were significantly improved by the exercise training: mMRC 2,7±0,9 vs. 2,3±1,2; SGRQ 45±15 vs 34±18; BDI-SF 4,2±5,1 vs. 2,7±4,3; TE 6,4±5,4 vs. 17,2±12,8 respectively at T0 and T12. The improvement of TE was significantly correlated to that of the SGRQ scores (r=0,4; P<0,001) and of the BDI-SF scores (r=-0,24; P=0,001). CONCLUSION: This home-based exercise training program improved dyspnoea, quality of life, depression and exercise capacity. The improvement of the TE and BDI-SF scores were correlated.

[IgG4-Related Disease: A rare cause of severe interstitial lung disease]. / La maladie associée aux IgG4 : une cause rare de pneumopathie infiltrante hypoxémiante sévère.

BACKGROUND: The intrathoracic manifestations of IgG4-related disease include a range of conditions and severity, and can on occasion cause acute respiratory failure as reported in the case described here. OBSERVATION: A 69-year-old male former smoker, was admitted to our hospital with dyspnea, fever, cough, fatigue, and a 3-month history of weight loss. He received high flow oxygen therapy and non-invasive ventilation for severe respiratory failure. Chest computed tomography revealed multifocal condensations and ground glass opacities, accompanied by thickening of the perilymphatic interstitium, mediastinal lymphadenopathy and bilateral pleural effusion. Elevated serum concentrations of IgG4 suggested an IgG4-Related Disease. He developed renal failure and underwent a renal biopsy. Histopathological analysis of which supported the diagnosis by showing dense lymphocytic infiltrate with a count of IgG4+ cells/hpf higher than 60, and storiform fibrosis - a swirling, "cartwheel" pattern of fibrosis which may have a patchy distribution. The patient responded well to steroid therapy. CONCLUSION: Although respiratory symptoms are usually mild in IgG4-relatd disease, thoracic features can evolve into acute respiratory failure with few extra thoracic manifestations.

Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.

[The impact of exposure to cigarette smoke on the haemodynamic response during exercise of patients under specific treatment for pulmonary arterial hypertension]. / Impact de l'exposition à la fumée de cigarette sur la réponse hémodynamique à l'exercice de patients sous traitement spécifique de l'HTAP.

INTRODUCTION: Pulmonary hypertension (PH) is a life-threatening haemodynamic condition associated with many disorders. In pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension, several treatments acting against pulmonary endothelial dysfunction have been shown to be effective. Exposure to cigarette smoke leads to endothelial dysfunction which is comparable to that observed in patients with PAH. The main objective was to investigate the difference in the haemodynamic changes during exercise in patients under specific treatment, from diagnosis (T0) to the first reassessment visit with a right heart catheterisation (T1), between those exposed or not exposed to cigarette smoke. MATERIALS AND METHODS: Between January 2002 and December 2018, all patients under specific treatment for PAH or chronic thromboembolic PH who underwent supine submaximal exercise assessment at T0 and T1 in our institution were asked specific questions about tobacco smoking. RESULTS: Overall (n=109), difference in mean isoflow mPAP was 19.0±15.4mmHg in patients exposed to tobacco smoke versus 21.3±16.6mmHg in unexposed patients (P=0.59). Median survival in exposed group was 83 months while in the unexposed group, median survival was 100 months (P=0.099). DISCUSSION: Our study did not show any significant difference in terms of haemodynamic changes during exercise between a group of patients under specific PH treatment exposed to cigarette smoke and a group unexposed. Endothelial dysfunction induced by smoke exposure does not appear to have a major impact on the response to the specific PH treatment.

[Eosinophilic pneumonia: A rare complication of sodium divalproate]. / Pneumopathie à éosinophiles : une complication rare du divalproate de sodium.

INTRODUCTION: Eosinophilic pneumonias are characterized by an increase in lung eosinophils. These disorders can be induced by drug reactions. CASE REPORT: A 57-year-old woman suffering from bipolar disorder and treated by sodium divalproate for more than 2 years was hospitalised in the department of respiratory medicine for dyspnoea and cough. The investigations showed severe hypoxaemia, airflow limitation, multiple ground-glass opacities and crazy paving on the chest CT-scan and a blood eosinophilia. A significant alveolar eosinophilia was found in the broncho-alveolar lavage. A complete assessment of possible causes was made. Finally, we made the diagnosis of eosinophilic pneumonia secondary to sodium divalproate. The treatment was stopped and systemic corticosteroid therapy was not introduced. The patient showed an improvement of her dyspnoea in a few days. Lung function and the CT-scan were normal within a few months. CONCLUSIONS: Sodium divalproate, frequently used in the treatment of bipolar disorder, is a rare cause of eosinophilic lung disease, even years after its introduction. Rapid diagnosis and withdrawal of treatment led to complete resolution in the reported case.

[Early determinants of chronic obstructive pulmonary disease: Lung regeneration, a new therapeutic target?] / Déterminants précoces de la bronchopneumopathie chronique obstructive : la régénération pulmonaire, une nouvelle piste thérapeutique ?

Chronic obstructive pulmonary disease, a disease of increasing incidence, is related mainly to smoking. Although symptoms only appear at adulthood, the disease can develop from early life events. For example, bronchopulmonary dysplasia, which occurs in preterm infants, is characterized by airspace enlargement and could lead to late lung consequences. Once the lesions are established, no curative treatment is available. Stimulating lung regeneration from endogenous stem cells is therefore an exciting research domain, particularly through the activation of the mesenchymal contingent located in the lung stem cell niche.

[A case of bronchiectasis due to light chain deposition disease]. / Histoire naturelle d'une forme bronchectasiante de la maladie à dépôts de chaînes légères.

INTRODUCTION: The natural history of orphan lung diseases is often unclear. We report the long-term follow-up of a case of bronchiectasis due to pulmonary non amyloid light chain deposition disease (LCDD). CASE REPORT: A 50-year-old woman who was a smoker, was diagnosed with diffuse thin walled bronchiectasis of uncertain origin after presenting with a respiratory tract infection. Ten years later, the combination of bronchiectasis, the appearance of pulmonary cysts and the identification of increased kappa free light chains evoked the diagnosis of pulmonary LCDD. The diagnosis was confirmed by lung biopsy. No immunoproliferative disorder was identified. During the 12 years follow-up, dyspnea worsened progressively and bronchiectasis and lung cysts extended leading to multicystic lung disease. Pulmonary function tests did not show any ventilatory defect but a small decrease in carbon monoxide transfer factor occurred. CONCLUSION: We describe the evolution of a rare presentation of isolated pulmonary LCDD, characterized by cystic diffuse atypical bronchiectasis with thin walls, associated with progressive cystic destruction of the lung parenchyma. The possibility of pulmonary LCDD should be considered in cases of atypical bronchiectasis of unknown etiology.

[Discrepancy between two methods of D-dimers measurement: one case of human anti-mouse antibody interference]. / Incohérence entre deux méthodes de dosage des D-dimères: un cas d'interférence d'anticorps humain anti-souris.

Quantification of D-dimers is the major biometry step in the diagnostic of an episode of the venous thromboembolic disease. The measurement of D-dimers can be performed with ELISA or immunoturbidimetric methods suited to emergency, using a mouse monoclonal antibody as capture and/or revelation antibody. Therefore, the presence in patient's plasma of human antibody mouse (HAMA) that binds the mouse antiglobulin used in immunoassays can lead to false negative or false positive results. In a young woman presenting repetitive thoracic pain suggestive of a pulmonary embolism, a major discrepancy was found between one result of D-dimers above the cut-off with an immunoturbidimetric method (STA Liatest D-DI; Diagnostica Stago) and one result below the cut-off with a sandwich method (Vidas D-Dimer Exclusion; bioMérieux). HAMA, which is known to be responsible for this type of discrepancy, was detected in the patient serum. The false positive result probably impaired with the management of patient. Taking in charge the patient should take into account the possible presence of this antibody. Interference by heterophilic antibodies is not easily detected by the laboratory. Even if their frequency is low, it remains a difficult problem for the biologist. Suspicion generally arises from inconsistency between the clinical data and immunoassay results. A good communication between physician and biologist should avoid to providing false negative or positive results.

[Tunnelled central venous catheter infection during treatment with epoprostenol]. / Infection de cathéter veineux central tunnelisé survenue sous traitement par époprosténol.

INTRODUCTION: Pulmonary arterial hypertension is a pulmonary vascular disease with a poor prognosis. Continuous intravenous treatment with prostacyclin analogues requires the placement of a tunnelled catheter. The occurrence of catheter-related infections in this context is unusual due to the alkaline pH of the prostacyclin analogue solutions. OBSERVATION: A 50-year-old patient with inherited pulmonary artery hypertension, treated with bosentan, sildenafil and epoprostenol, experienced generalized malaise associated with a weight loss of 9kg over a 12-month period without evidence of a source of infection or malignancy. There was no evidence of hemodynamic disturbance. The diagnosis was made after 1 year of follow-up, when the patient presented with a 38° fever and a biological inflammatory syndrome. Repeated peripheral blood cultures were positive for Dietzia, an alkalophilic coryneform bacillus. The patient's condition responded favourably to antibiotic therapy. CONCLUSION: Infection of a tunneled intravenous catheter should be considered in the case of non-specific symptoms or where there is evidence of sepsis, in patients treated with intravenous prostacyclin analogues administered intravenously. In this context, the laboratory should be warned to search for slow-growing organisms.

[Drug-induced interstitial pneumonitis due to avelumab: A case report]. / Pneumopathie interstitielle médicamenteuse à l'avelumab : à propos d'un cas.

INTRODUCTION: The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class. CASE REPORT: A 66-year-old woman, ex-smoker, had been treated with avelumab and axitinib since November 2016 for renal cell cancer. Interstitial pneumonitis was discovered accidentally 4 months after the beginning of the treatment, with ground glass opacities, intra-lobular crosslinking and adenopathy of the 4R zone on the CT scan. An exhaustive assessment did not reveal any respiratory function defect or an infectious or immunological cause. The radiological abnormalities regressed spontaneously after cessation of treatment confirming the diagnosis of drug-induced pneumonitis. CONCLUSION: Avelumab can induce interstitial lung disease. The mechanism is uncertain and requires further studies. Monitoring of respiratory function and CT scanning are necessary for its early management.

[Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary arterial hypertension]. / Évaluation de l'IRM cardiaque dans le suivi des patients ayant une hypertension artérielle pulmonaire (EVITA). IRM cardiaque dans le suivi de l'hypertension artérielle pulmonaire.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index<2.5L/min/m2 or a right atrial pressure≥8mm Hg measured with RHC compared with a cardiac index<2.5L/min/m2 or right ventricle ejection fraction<35% or an absolute decrease of 10% from the previous measurement with cMRI. Exact values of sensitivity, specificity and 95% confidence intervals will be computed. A population of 180 subjects will have a power of 90% with an α risk of 5%. Univariate and multivariate Cox analysis will allow answering to the secondary objectives. We expect to demonstrate that cMRI could be partly used instead of RHC in the follow up of patients with PAH.

[Pulmonary hypertension of chronic respiratory disease]. / Hypertension pulmonaire des affections respiratoires chroniques.

Pulmonary hypertension of chronic respiratory disease is defined as elevation of the mean resting pulmonary artery pressure to over 20 mm Hg. It is the commonest cause of pre-capillary pulmonary hypertension on account of the high prevalence of chronic obstructive pulmonary disease. It is primarily due to alveolar hypoxia that leads to remodelling of the distal pulmonary vasculature and consequently to an increase in pulmonary resistance. It is not as severe as idiopathic pulmonary hypertension. The mean pulmonary artery pressure is usually moderately increased (20-35 mm Hg) when patients are seen during a stable period of the disease. There are, however, more severe cases of pulmonary hypertension called, in some cases, disproportionate but these are uncommon. Increased right ventricular afterload can lead to the development of right ventricular failure that is a definite prognostic factor. The clinical symptoms of pulmonary hypertension are at a secondary level compared with those of the causal disease. Non-invasive diagnosis depends on Doppler echocardiography. Currently the most effective treatment is long term oxygen therapy (16-18 hr/24 hr). This improves or, at least stabilises, the pulmonary hypertension.

[A rare tracheal tumour: solitary fibroma]. / Une cause exceptionnelle de tumeur trachéale: la tumeur fibreuse solitaire.

INTRODUCTION: Solitary fibromas are rare anatomo-pathological entities, described initially in the pleural cavity. The mesenchymal origin of these tumours explains their widespread distribution. CASE REPORT: The authors report a case of solitary fibroma of the trachea in a woman of 30 years of age, presenting as acute respiratory distress and preceded by a 2 year history of episodes of dyspnoea diagnosed as unstable asthma. CT and MRI imaging showed evidence of a localised tracheal tumour without mediastinal infiltration. The images and macroscopic appearances were non-specific. Bronchoscopic resection of the tumour gave immediate relief of the symptoms. Histology, which was positive for anti-CD34 antibodies and negative for epithelial, muscular and neurological markers, led to a diagnosis of solitary fibroma with no evidence of malignancy. CONCLUSION: To our knowledge, this observation is the first description of a primary solitary fibroma localised to the trachea. The clinical and radiological features are no different from those of other tracheal tumours. After excision, the prognosis is good but long-term follow-up is necessary on account of the risk of local recurrence or metastasis.

[Pulmonary infection with Mycobacterium malmoense. Difficulties in diagnosis and treatment]. / Infection pulmonaire à Mycobacterium malmoense. Difficultés diagnostiques et de thérapeutiques.

INTRODUCTION: Pulmonary infection due to Mycobacterium malmoense can be difficult to diagnose. These difficulties can be responsible for a delay in the implementation of optimal treatment. Moreover, the treatment is not standardized. OBSERVATION: We report the case of a 56-year-old patient who developed a Mycobacterium malmoense pulmonary infection whose diagnosis was delayed due to initial suspicion of pulmonary Mycobacterium tuberculosis infection. Once the diagnosis was confirmed, the patient was treated empirically with rifampicin, ethambutol, and clarithromycin for 12 months after culture conversion, giving a total of 15 months. The clinical and radiological outcomes were favorable. DISCUSSION: This clinical case highlights the difficulties of diagnosing pulmonary atypical mycobacterial infection according to the American Thoracic Society criteria, particularly Mycobacterium malmoense, a non-tuberculous mycobacterium (NTM) quite uncommon in France. Currently, there are new diagnostic techniques such as GenoType Mycobacteria Direct®. The second issue is the poorly standardized treatment of this NTM and many others, that are based on the recommendations of the British Thoracic Society. A national register has been set up by the MycoMed network, based essentially on the work of microbiologists but this register is unfortunately not exhaustive. CONCLUSION: A more systematic reporting strategy could allow cohort studies and therefore provide us with data on the most efficient drugs in the treatment of the rarest NTM infections.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.