Evolving to a single inhaler extrafine LABA/LAMA/ICS - Inhalation technique and adherence at the heart of COPD patient care (TRIVOLVE).

OBJECTIVE: Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 µg), formoterol fumarate (FF, 5 µg) and glycopyrronium (G, 9 µg)) in combination with inhalation technique training. METHODS: A total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up. RESULTS: Before switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased. CONCLUSIONS: This observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.

[Duodenal bleeding due to metastasis from lung adenocarcinoma controlled by radiotherapy: A case report and literature review]. / Saignement duodénal dû à une métastase d'un cancer pulmonaire contrôlé par radiothérapie : cas clinique et revue de la littérature.

INTRODUCTION: Gastrointestinal (GI) metastases in lung cancer rarely occur. CASE REPORT: We report here the case of a 43-year-old male active smoker who was admitted to our hospital for cough, abdominal pain and melena. Initial investigations revealed poorly differentiated adenocarcinoma of the superior-right lobe of the lung: positive for thyroid transcription factor-1 and negative for protein p40 and for antigen CD56, with peritoneal, adrenal and cerebral metastasis, as well as anemia requiring major transfusion support. Over 50% of cells were positive for PDL-1, and ALK gene rearrangement was detected. GI endoscopy showed a large ulcerated nodular lesion of the genu superius with active intermittent bleeding, as well as an undifferentiated carcinoma with positivity for CK AE1/AE3 and TTF-1, and negativity for CD117, corresponding to metastatic invasion originating from lung carcinoma. Palliative immunotherapy with pembrolizumab was proposed, followed by targeted therapy with brigatinib. Gastrointestinal bleeding was controlled with a single 8Gy dose of haemostatic radiotherapy. CONCLUSION: GI metastases are rare in lung cancer and present nonspecific symptoms and signs but no characteristic endoscopic features. GI bleeding is a common revelatory complication. Pathological and immunohistological findings are critical to diagnosis. Local treatment is usually guided by the occurrence of complications. In addition to surgery and systemic therapies, palliative radiotherapy may contribute to bleeding control. However, it must be used cautiously, given a present-day lack of evidence and the pronounced radiosensitivity of certain gastrointestinal tract segments.

[Benralizumab in cases of eosinophilic granulomatosis with polyangiitis]. / Diagnostic d'une granulomatose éosinophilique avec polyangéite sous benralizumab.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare necrotizing vasculitis affecting small vessels and associated with severe asthma and eosinophilia. Monoclonal antibodies blocking the IL-5 signaling pathway, one example being benralizumab, decrease the proliferation of eosinophils and represent an effective treatment in severe eosinophilic asthma. They are a therapeutic option currently studied for EGPA. We report the paradoxical clinical case of EGPA appearing following the initiation of treatment with benralizumab (anti-IL-5R monoclonal antibody). CASE REPORT: We describe the case of a 66-year-old female patient with severe asthma. Following the initiation of benralizumab, she showed deterioration of her general condition, associated with severe peripheral neuropathy of the lower limbs. At the same time, she developed massive hypereosinophilia. After an extensive workup, the patient was eventually diagnosed with an EGPA with multisystem involvement. Benralizumab was stopped and a course of high dose corticosteroids and immunosuppressants was initiated, enabling slow clinical recovery. CONCLUSION: Anti-IL5 monoclonal antibodies, including benralizumab, are being investigated for new therapeutic indications, including EGPA. Paradoxically, a few rare cases of EGPA associated with these molecules have been reported in the literature. The causal link of this association remains hypothetical. Close monitoring of patients on benralizumab consequently seems indispensable.

Chronic oral corticosteroids use and persistent eosinophilia in severe asthmatics from the Belgian severe asthma registry.

BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

[Pulmonary embolism and inferior vena cava agenesis: An unusual association]. / Embolie pulmonaire et agénésie de veine cave inférieure : une association inhabituelle.

INTRODUCTION: Inferior vena cava agenesis is a rare congenital anomaly, generally associated with thrombophilic conditions, and a predisposing factor for deep venous thrombosis (DVT), rarely complicated by pulmonary embolism, in a young population with atypical clinical features and frequent absence of risk factors. CASE REPORT: We report the case of a 30-year-old woman who developed a right iliac DVT, initially presenting as a low back pain and complicated by a pulmonary embolism, 8 months after a sleeve gastrectomy. Chest CT angiography revealed abnormalities that led to the diagnosis of inferior vena cava agenesis. Thrombophilic screening showed a heterozygous prothrombin gene mutation G20210A and hyperhomocysteinemia. The patient was treated with rivaroxaban with good results after 2 years of follow-up. CONCLUSIONS: In young patients without risk factors developing a deep venous thrombosis, an inferior vena cava anomaly should be considered. Although no therapeutic consensus has been currently established, inferior vena cava agenesis seems to be associated with a high prevalence of thrombophilic disorders. Screening could be useful, particularly in patients with a thrombotic family history.

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

UNLABELLED: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. METHODS: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. RESULTS: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. CONCLUSION: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Mycobacterium marinum infection causing extensive tissue destruction in a hypoxic COPD patient.

We report a skin Mycobacterium marinum infection presenting as wide ulcerative lesions of the arm (4 cm for the widest) in a hypoxic COPD patient who takes 4 mg methylprednisolone daily and higher doses during exacerbations. Diagnostic delay as well as glucocorticoid use could be responsible for the extension of the lesions. Clinical resolution occurred after three months of antibiotic therapy. Extensive ulcerative lesions are uncommon in Mycobacterium marinum infection in an immunocompetent host. This case emphasizes the potential and unusual harmful effect of long-term glucocorticoid therapy used in obstructive lung disease on the spread of Mycobacterium marinum infection.

Exhaled nitric oxide as a marker of asthma control in smoking patients.

Exhaled nitric oxide fraction (F(eNO)), which is a reliable marker of eosinophilic airway inflammation, is partially suppressed by tobacco smoking. Consequently, its potential as a biomarker in asthma management has never been evaluated in smoking patients. In the present study, the authors tested the validity of F(eNO) to predict asthma control in this population. F(eNO) and the Asthma Control Questionnaire (ACQ) were recorded at least once in 411 nonsmoking (345 with at least two visits) and 59 smoking (51 with at least two visits) asthma patients. Despite similar mean ACQ scores (1.5 versus 1.7), F(eNO) was reduced in smoking asthmatics (18.1 ppb versus 33.7 ppb). A decrease in F(eNO) of <20% precludes asthma control improvement in nonsmoking (negative predictive value (NPV) 78%) and in smoking patients (NPV 72%). An increase in F(eNO) <30% is unlikely to be associated with deterioration in asthma control in both groups of patients (NPV = 86% and 84% in nonsmoking and smoking patients, respectively). It is concluded that, even in smokers, sequential changes in F(eNO) have a relationship with asthma control. The present study is the first to indicate that cigarette smoking does not obviate the clinical value of measuring F(eNO) in asthma among smokers.

[Subcutaneous emphysema in a borderline patient]. / Emphysème sous-cutané et troubles de la personnalité

This report concerns a 31-year-old woman. It is an intricate case including bilateral self-induced pneumoparotitis, cervical and facial subcutaneous emphysema and limited pneumomediastinum. Besides, this borderline patient simulated asthma attacks. The clinical picture was characteristic of Munchausen's syndrome with multiple hospitalisations in various hospitals, automutilations and intentional production of physical symptoms. The diagnosis and the treatment are discussed.

Pulmonary nodular lesions in a 70-year-old man.

Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon but increasingly recognized clinicopathologic syndrome. This report illustrates a proteiform clinical presentation of BOOP in a 70-year-old patient with cough, low-grade fever, weight loss, and hemoptysis. Chest radiograph and computed tomography (CT scan) showed nodular lesions. A video-assisted thoracoscopic procedure for biopsy of the largest nodule was performed at the end of an extensive work-up. A diagnosis of BOOP was established and, because of persistent symptomatology, corticosteroid therapy was initiated. This observation illustrates that the clinical and radiological findings of BOOP are non-specific and can sometimes mimic primary and/or secondary pulmonary malignancies.

Persistence of the insecticide Dimilin 45 ODC on conifer forest foliage in an Atlantic-climate ecosystem.

The oil formulation of diflubenzuron (Dimilin 45 ODC) persisted for 10-12 weeks on the foliage of a conifer forest in an Atlantic-climate ecosystem. Within 22-30 days following treatment, 55-80% of the insecticide had been removed from the foliage. During this period, the concentration of diflubenzuron was higher than 370 ng g(-1). Aerial application at 56.3 g of Al ha(-1) resulted in deposition levels of the insecticide ranging from 867.5 to 1824.4 ng g(-1), depending upon forest characteristics. The results showed that aerial application is only a suitable technique for the treatment of forest areas with dense foliage and/or high tree density and no more than 15% of tree-free area. The only metabolite detected was 2,6-difluorobenzamide, and this persisted on foliage until the first rainfalls occurred. An empirical mathematical correlation was found to express the influence of meteorological variables--rainfall, solar radiation and temperature--on the persistence of the insecticide. These results suggested that degradation of diflubenzuron on foliage could be due to photodegradation. Some recommendations were made to optimize the deposition of the insecticide on foliage and to minimize its persistence and the off-site spray drift.

Bronchoscopic balloon dilatation in the combined management of postintubation stenosis of the trachea in adults.

Bronchoscopic balloon dilatation (BBD) using angioplasty balloon catheters has been employed successfully in the treatment of tracheobronchial stenoses in children and has worked with variable success in adults with bronchial stenosis. In adults with tracheal stenosis, BBD only has been reported anecdotally. In this study, experience with BBD using a valvuloplasty balloon catheter in the combined treatment (with Nd-YAG laser photoresection and stenting) of severe benign postintubation tracheal stenoses in three adults is delineated. BBD was particularly successful in establishing tracheal patency when laser photoresection was contraindicated or was too dangerous; BBD allowed easy insertion of tracheal stents and the "opening" of folded silicone stents. BBD is a simple, inexpensive, safe, and efficient adjunct in the combined treatment of severe postintubation rigid tracheal stenosis in selected adults.

Sternomastoid muscle size and strength in patients with severe chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) imposes a major strain on the respiratory muscle pump, and it is conventionally thought that the inspiratory muscles of the neck adapt to this chronic overload by developing hypertrophy. Yet previous anthropometric studies have shown atrophy of the sternomastoid muscles. To solve this discrepancy, we have measured the cross-sectional area of these muscles by computed tomography. Ten stable patients with severe airflow obstruction (FEV1 = 0.76 +/- 0.12 L) and hyperinflation (FRC = 210 +/- 29% of predicted) and 10 control subjects matched for age, sex, and height were studied. The sternomastoid cross-sectional area in the patients averaged (mean +/- SD) 4.29 +/- 1.48 cm2, and that in the control subjects was 3.96 +/- 0.82 cm2. This small difference could be entirely accounted for by hyperinflation, and it was not statistically significant. Sternomastoid muscle torque in patients was also similar to that in the control subjects. In patients with severe COPD, therefore, the sternomastoid muscles are essentially normal. As a corollary, their frequent prominence on clinical examination is only apparent.

[Pulmonary embolism and pregnancy: report of a case; review of the literature]. / Embolie pulmonaire et grossesse: à propos d'une observation; revue de la littérature.

Pulmonary embolism occurring during pregnancy is a rare accident but that still brings about a high mother mortality; it seems to be five to six times more frequent during the pregnancy and the post-partum than for non-parturient women who don't take any estro-progestogens, pulmonary embolism would involve complications for 0.5/1000 pregnancies before delivery. As it presents a lot of diagnostic problems, it is under-estimated. The vascular radiological examinations expose the foetus or embryo to considerable radiation and to a risk of foetal hypothyroidism leading to backwardness. The lung perfusion scanning has the advantage of not injecting iodine but is not specific. Fortunately, some medical examinations such as plethysmography or Doppler echography are safe and can also guide the clinician. As far as therapy is concerned, intravenous heparin is the first intention treatment, it can be replaced subsequently by subcutaneous heparin (low molecular weight heparin). In case of heavy pulmonary embolism endangering the vital prognosis of the patient, in case of clinical or biological resistance to the medical treatment, it could be necessary to perform a pulmonary embolectomy with, if necessary, vena cava interruption with insertion of a mechanical filter.

Neck muscle activity in patients with severe chronic obstructive pulmonary disease.

The present studies were designed to assess the pattern of activity and the frequency of activation of the neck muscles in patients with chronic obstructive pulmonary disease (COPD). Using concentric needle electrodes, we thus recorded the electromyograms of the scalene, sternocleidomastoid, and trapezius muscles during resting breathing in 40 stable patients with severe chronic airflow obstruction (FEV1 = 0.69 +/- 0.18 L) and hyperinflation (FRC = 228 +/- 40% of predicted); 17 patients were hypercapnic at rest. When breathing in the seated posture, all patients (100%) had strong inspiratory contraction of the scalenes. In contrast, no patient showed inspiratory activity in the trapezius, and only four patients (10%) showed definite, invariable inspiratory activity in the sternocleidomastoid. These two muscles were silent in the supine posture as well, even though the adoption of this posture was associated with an increase in dyspnea in most patients. We conclude, therefore, that in contrast to conventional thinking, most stable patients with severe COPD do not use the sternocleidomastoids or the trapezii when breathing at rest. Additional measurements indicated that the sternocleidomastoid inspiratory activity previously recorded in such patients was in general caused by a cross-contamination from surrounding muscles.