Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Usefulness of omalizumab in ten patients with severe occupational asthma.

BACKGROUND: The management of severe occupational asthma (OA) remains problematic and new alternative treatments providing better disease control are required, ideally enabling affected individuals to remain in their job. METHODS: Ten patients with severe uncontrolled OA were treated with the monoclonal anti-IgE antibody omalizumab. In six cases the causative agent was a high molecular weight (HMW) compound and in four cases it was a low molecular weight (LMW) chemical. All of the patients had well documented OA despite workplace adjustments. RESULTS: During treatment, nine patients exhibited a lower rate of asthma exacerbations and used less oral or inhaled corticosteroids. Seven patients were able to continue working at the same workplace as before treatment. CONCLUSION: We have demonstrated that omalizumab is a potential treatment for severe uncontrolled OA and enabled seven of the ten patients in the study to remain in their job.

[Antibiotic strategy in pleural empyema in children: Consensus by the DELPHI method]. / Stratégie antibiotique dans les pleurésies en pédiatrie : consensus par méthode DELPHI.

INTRODUCTION: The evolution of the microbial epidemiology of pleuropulmonary infections complicating community-acquired pneumonia has resulted in a change in empirical or targeted antibiotic therapy in children in the post Prevenar 13 era. The three main pathogens involved in pleural empyema in children are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus. METHODS: A questionnaire according to the DELPHI method was sent to experts in the field (paediatric pulmonologists and infectious disease specialists) in France with the purpose of reaching a consensus on the conservative antibiotic treatment of pleural empyema in children. Two rounds were completed as part of this DELPHI process. RESULTS: Our work has shown that in the absence of clinical signs of severity, the prescription of an intravenous monotherapy is consensual but there is no agreement on the choice of drug to use. A consensus was also reached on treatment adjustment based on the results of blood cultures, the non-systematic use of a combination therapy, the need for continued oral therapy and the lack of impact of pleural drainage on infection control. On the other hand, after the second round of DELPHI, there was no consensus on the duration of intravenous antibiotic therapy and on the treatment of severe pleural empyema, especially when caused by Staphylococci. CONCLUSIONS: The result of this work highlights the needed for new French recommendations based on the evolution of microbial epidemiology in the post PCV13 era.

[Physical activity in severe asthma: Results of the FASE-CPHG Study]. / Activité physique et asthme sévère : résultats de l'étude FASE-CPHG.

INTRODUCTION: Data on physical activity in severe asthma are scarce. From May 2016 to June 2017, 1502 adult patients with severe asthma visiting a pulmonologist practicing in one of the 104 non-academic hospitals participating in the study were included in this prospective, cross-sectional, multicenter study, provided they gave consent. Physical activity was classified according to 4 levels: 1 (no activity), 2 (occasional), 3 (regular), or 4 (frequent). Clinical and therapeutic parameters were described according to these levels. RESULTS: Respectively, 440, 528, 323, and 99 patients had physical activity of level 1, 2, 3, and 4. The percentage of patients with controlled asthma increased with physical activity. Treatment adherence did not differ with physical activity. Percentages of obese patients, patients with FEV1 <60%, and patients with anxiety, depressive syndrome, gastro-esophageal reflux disease, arterial hypertension, diabetes, obstructive sleep apnoea-hypopnoea syndrome, and osteoporosis decreased with physical activity. Respiratory rehabilitation was offered to only 5% of patients. CONCLUSIONS: In this large study, physical activity is associated with disease control in severe asthma and with less comorbidity. Its practice should be encouraged and respiratory rehabilitation offered more often.

[The effects of inhaled steroids withdrawal in COPD]. / Impact du sevrage des corticostéroïdes inhalés dans la BPCO.

The key pathophysiological feature of chronic obstructive pulmonary disease (COPD) is an abnormal inflammatory bronchial reaction after inhalation of toxic substances. The priority is the avoidance of such toxic inhalations, but the use of anti-inflammatory drugs also seems appropriate, especially corticosteroids that are the sole anti-inflammatory drug available for this purpose in France. The risks associated with the prolonged use of these parenteral drugs are well known. Inhalation is therefore the optimal route, but inhaled drugs may also lead to adverse consequences. In COPD, there is an inhaled corticosteroids overuse, and a non-satisfactory respect of the guidelines. Consequently, their withdrawal should be considered. We reviewed seven clinical studies dealing with inhaled corticosteroids withdrawal in patients with COPD and found that included populations were heterogenous with different concomitant treatments. In non-frequent exacerbators receiving inhaled corticosteroids outside the recommendations, withdrawal appears to be safe under a well-managed bronchodilator treatment. In patients with severe COPD and frequent exacerbations, the risk of acute respiratory event is low when they receive concomitant optimal inhaled bronchodilators. However, other risks may be observed (declining lung function, quality of life) and a discussion of each case should be performed, especially in case of COPD and asthma overlap.

[The place of inhaled corticosteroids in COPD]. / Place des corticostéroïdes inhalés dans la BPCO.

INTRODUCTION: Clinical trials have provided some evidence of a favorable effect of inhaled corticosteroids on the frequency of exacerbations and on the quality of life of patients with chronic obstructive pulmonary disease (COPD). In contrast, ICS have little or no impact on lung function decline and on mortality. STATE OF THE ART: Inhaled corticosteroids are recommended only in a minority of COPD patients, those with severe disease and repeated exacerbations and probably those with the COPD and asthma overlap syndrome. However, surveys indicate that these drugs are inappropriately prescribed in a large population of patients with COPD. Overtreatment with inhaled corticosteroids exposes these patients to an increased risk of potentially severe side-effects such as pneumonia, osteoporosis, and oropharyngeal candidiasis. Moreover, it represents a major waste of health-care spending. CONCLUSION: Primary care physicians as well as pulmonologists should be better aware of the benefits as well as the side-effects and costs of inhaled corticosteroids.

[Non-tuberculous mycobacterial infection of a totally implanted perfusion device]. / Infection à mycobactérie non tuberculeuse d'une chambre implantable pour perfusion.

INTRODUCTION: Catheter-related infection by non-tuberculous mycobacteria is rare but difficult to diagnose and the treatment is not standardized. CASE REPORT: A 64-year-old woman treated for lung cancer with intravenous chemotherapy developed an infection of her totally implanted perfusion device with Mycobacterium chelonae. The infection was cured after surgical removal of the device and treatment with oral clarithromycin. CONCLUSION: Mycobacteria may infect vascular access devices. Rapid diagnosis of such infections allows early treatment.

Pulmonary arteriovenous malformations.

OBJECTIVE: Helical CT scan (HCT), a noninvasive method, can detect pulmonary arteriovenous malformations (PAVMs). Its sensitivity is superior to that of global digitalized angiography, but patients receive a significant dose of radiation during diagnostic HCT. We compared HCT to contrast-enhanced pulmonary magnetic resonance angiography (CEMRA), a new noninvasive radiation-free method, in the diagnosis of PAVMs. PATIENTS AND METHODS: Five consecutive patients with PAVMs underwent HCT, CEMRA, and pulmonary artery digital subtraction angiography (PADSA). CEMRA was performed during the pulmonary arterial phase of an IV bolus of gadolinium. PADSA was performed during the embolization procedure. All images were examined for PAVMs. The site and size of aneurysms were specified, as well as the diameter of the vascular pedicles. RESULTS: Thirty PAVMs were detected by CEMRA and 38 by HCT. All 20 PAVMs at least 5 mm in diameter and 10 of the 18 PAVMs < 5 mm in diameter identified on HCT were also identified by CEMRA. Whatever the site, all PAVMs with a feeding artery diameter of at least 3 mm (ie, PAVMs with clinical consequences) were detected by CEMRA. No false-positive results were obtained with CEMRA. CEMRA therefore had a sensitivity of 78% and a specificity of 100%. CONCLUSIONS: CEMRA, a nonionizing and noninvasive procedure, has high sensitivity and specificity for the diagnosis of clinically relevant PAVMs.

[Nosocomial pneumonia]. / Pneumopathies nosocomiales.

Second cause of nosocomial infections and certainly the most serious, pneumonia concerns nearly 1% of all hospitalized patients. The need for intensive care, especially mechanical ventilation, is the leading risk factor for acquiring nosocomial pneumonia. Clinical and radiological data are contributive but insufficient for diagnosis and correct selection of antibiotics. Many germs are potentially accountable for these diseases, especially Pseudomonas and Staphylococcus. The endobronchial protected brush has been considered as the gold standard for diagnosis by the fifth consensus report of SRDLF (Société de Réanimation de Langue Française). Other methods are currently proposed which are less traumatic, cheaper, easier to use and give quicker results, but their sensitivity and specificity are debated. The bacteriological results of these searches are precious guides to choose curative antibiotics. The prevention of nosocomial pneumonia has become an accepted priority for public health.

[Pulmonary artery hypertension due to tumor micro-embolism]. / Hypertension artérielle pulmonaire par micro-embolies tumorales.

We report the case of a 37 years old woman with a past history of a chondrosarcoma who was admitted to hospital for acute pulmonary hypertension which proved rapidly fatal; autopsy confirmed that the etiology was tumour microemboli rising from a single cardiac metastases from her chondrosarcoma. The originality of this case report lies in the origin of the microemboli and the way in which they presented as a recurrence of the cancer.

[Primary pleural lymphoma: a rare complication of tuberculosis pleural sequelae]. / Lymphome pleural primitif: une complication rare des séquelles pleurales de tuberculose.

We report two cases of malignant lymphoma of B phenotype occurring after therapeutic pneumothorax for tuberculosis. In both cases, outcome was fatal without time for specific treatment. Mainly reported in Japan, this pathology seems to be less frequent in western countries. As for B phenotype lymphoma associated with immunodeficiency, association with Epstein Barr virus is reported. Definite diagnosis is difficult and requires surgical biopsy. Prognosis remains poor with a survival ranging from 3 to 6 month.

[Drug-induced pneumopathies accompanied by acute respiratory insufficiency]. / Pneumopathies médicamenteuses s'accompagnant d'insuffisance respiratoire aiguë.

Drug induced pneumonias accompanying acute respiratory failure are defined by a delay in presentation of less two months and severe hypoxaemia (PaO2 < 60 mmHg in ambient air). They are poorly indexed, often poorly understood by the clinician and pose difficult problems both of diagnosis and treatment. This general review touches successively on hypoxaemic drug induced pneumonia observed in oncology and haematology then those observed outside this very specific context. In each of the two groups five questions are posed: 1) Which patients? 2) Which clinical patterns? 3) What initial diagnostic discussion? 4) Which successful elements support the drug induced hypothesis? 5) What outcome? The replies obtained were compared to case reports from the literature (188 references) or from recent general reviews concerned more specifically with the hypoxaemic forms.

[Single-lung transplant in chronic obstructive disease]. / Greffes monopulmonaires chez les obstructifs chroniques.

The feasibility and the good immediate acceptability of unilateral lung transplants in the patients with obstructive respiratory problems have recently been demonstrated and since the initial reports, some hundreds of lung transplants have been performed in various parts of the world for this indication. Nevertheless, few results of respiratory function are currently available in the medium term. We report these in a series of 20 patients with severe obstruction who were given single lung transplants. The actual probability of survival for 1 and 2 years was 75 and 70% respectively with 4 peri-operative deaths and 2 later deaths. In the 16 survivors of more than 6 months, in relation to the pre-operative values, a significant improvement was observed 3 months after the graft in the FEV1 which rose from 17 +/- 6 to 53 +/- 13% of the predicted values. The PaO2 rose from 52 +/- 10 to 81 +/- 3 mmHg. The distance covered on the six minute walking test went from 99 +/- 84 m before the graft to 587 +/- 147 m 6 months after the operation. In addition to the improved distance, the lung function was stable in a group of patients as the months went by, although there was a fall in the respiratory function in others with the appearance of the syndrome of bronchiolitis obliterans or in 2 patients with bronchial complications. The four patients with severe deterioration in the graft function were re-transplanted with a good clinical result in three of them, the fourth dying in the immediate post-operative period. We conclude that single lung transplant represents an effective treatment both in the short and medium term in patients with chronic airflow obstruction.

[Pulmonary emphysema: surgical indications]. / Emphysème pulmonaire: indications chirurgicales.

Surgery for pulmonary emphysema, with the exception of lung transplantation, is limited at present to resection of the emphysematous areas. The resection of a unique bulla within an otherwise healthy parenchyma can be indicated in case of complications but rarely in asymptomatic patients. When the bullae are large (i.e. volume greater than one-third of the hemithorax) in a patient suffering from diffuse emphysema, bullectomy is the ideal indication. Mortality varies from 0 to 10%, essentially due to infection or acute respiratory failure. In most patients, the subjective improvement in terms of dyspnea and the objective improvement as measured by spirometry remains significative up to 5 years after surgery. Inversely, surgical resection is classically considered to be contraindicated in patients with small poorly-limited bullae. Recent data would however question this idea since subjective and objective improvement after reduction of the lung volume is still present 1 year after surgery in most patients, even those with severe obstruction. The mechanism is probably related to increased elastic recoil. Even if only temporary improvement can be achieved for a few years, the persisting course of emphysema would suggest that volume reduction should always be entertained as an alternative before lung transplantation.

[Evaluation of occupational exposures in lung cancer]. / Evaluation des expositions professionnelles et cancer bronchopulmonaire.

Occupational lung cancers are underestimated by the number of cases compensated in the French National Insurance System. Rules of compensation of occupational diseases were recently modified in France. Therefore a study was conducted on incident cases of lung cancer in a general hospital in the Paris area. The aim was to evaluate the exposure to carcinogens using data of a detailed specific occupational questionnaire, and to determine the number of cases who could receive compensation. Two hundred and seven subjects (171 males, 36 females, mean age = 64.5 years) were eligible in 1996, and 122 had an occupational questionnaire. Definite exposure to one or more occupational carcinogens in at least one job was identified in 50 subjects, the most frequent agent was asbestos (42 subjects). Claim for compensation was done in 32 subjects, mainly for asbestos (30 subjects). This study emphasizes the frequency of occupational exposure to carcinogens, and the usefulness of systematic occupational questionnaire in subjects having lung cancer. Social and financial consequences are important for these subjects. Further studies are needed, with recruitement of control subjects to allow calculation of the attributable risk to occupational factors in lung cancer.

[A mediastinal opacity in a patient with cirrhosis]. / Opacité médiastinale chez un patient cirrhotique.

Radiological mediastinal shadows have numerous causes. Paraesophageal varices might be revealed by such radiological findings. We described herein the case of a patient with radiological mediastinal opacity occurring after sclerotherapy that was finally related to esophageal varices.

[Acute respiratory distress in a patient with sickle-cell anemia]. / Détresse respiratoire aiguë chez une patiente drépanocytaire.

The acute chest syndrome is a frequent complications of sickle-cell disease characterized by chest pain, fever, and new infiltrate on chest x-ray image. Pathophysiologic factors appear to be multifactorial and better known. We report the case of a 28-year-old woman with homozygous sickle cell anemia who developed acute chest syndrome probably secondary to fat embolism.

[Computed tomographic diagnosis of a fortuitously discovered opacity]. / Diagnostic tomodensitométrique d'une opacité de découverte fortuite.

We report a case of pleuroparietal lipoma discovered fortuitously. Despite the small size, the diagnosis was obtained with computed tomography using a rigorous protocol demonstrating a negative density corresponding to fat tissue. A series of slices sufficiently thin to avoid a partial volume effect was required to obtain reliable measurements. In case of doubt, magnetic resonance imaging would be indicated.