[Selection of lung transplant candidates in France in 2019]. / Sélection des candidats à la transplantation pulmonaire en France en 2019.

INTRODUCTION: In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time. BACKGROUND: The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment. OUTLOOK AND CONCLUSION: These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation.

[Limitations of active therapeutic and palliative care in chronic respiratory disease]. / Intensité des soins lors des exacerbations et des complications des pathologies respiratoires chroniques.

The issue of intensive and palliative care in patients with chronic disease frequently arises. This review aims to describe the prognostic factors of chronic respiratory diseases in stable and in acute situations in order to improve the management of these complex situations. The various laws on patients' rights provide a legal framework and define the concept of unreasonable obstinacy. For patients with chronic obstructive pulmonary disease, the most robust decision factors are good knowledge of the respiratory disease, the comorbidities, the history of previous exacerbations and patient preferences. In the case of idiopathic pulmonary fibrosis, it is necessary to know if there is a prospect of transplantation and to assess the reversibility of the respiratory distress. In the case of amyotrophic lateral sclerosis, treatment decisions depend on the presence of advance directives about the use of intubation and tracheostomy. For lung cancer patients, general condition, cancer history and the tumor treatment plan are important factors. A multidisciplinary discussion that takes into account the patient's medical history, wishes and the current state of knowledge permits the taking of a coherent decision.

Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis.

Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion\Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion\Serion kit (P = 0.04). The Bordier and Bio-Rad kits had similar specificity (P = 0.8), both higher than that of the Virion\Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion\Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.

[Severe uncontrolled asthma in patients over 75 years old: Treatment with omalizumab]. / Asthme sévère mal contrôlé de sujets de plus de 75 ans : traitement par omalizumab.

INTRODUCTION: With an aging population and an increase in the prevalence of asthma, this disease is becoming more common in the elderly. Nevertheless, the management of severe asthma can be complex, due to an increased risk of uncontrolled disease in patients over 65 years old and partly to the inherent characteristics of old age: comorbidities, underestimation of the role of allergies, poor adherence, difficulties with inhalation devices, etc. CASE REPORTS: We report two cases of women over 75 with severe persistent allergic asthma not controlled by high doses of inhaled corticosteroids and long-acting beta-2-agonists in whom treatment with omalizumab was initiated. Following treatment with omalizumab a decrease in the number and severity of exacerbations, improved asthma control and dose reduction or discontinuation of systemic corticosteroids were observed. The tolerance of omalizumab was good in both cases. CONCLUSIONS: Omalizumab is to be considered an effective and well-tolerated therapeutic option for elderly patients with inadequately controlled severe allergic asthma.

Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus.

Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.

Management of voriconazole hepatotoxicity in a lung transplant patient.

Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46-year-old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known dose-dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively.

Multiple aggressive squamous cell carcinomas associated with prolonged voriconazole therapy in four immunocompromised patients.

Rare squamous cell carcinoma (SCC) cases associated with voriconazole therapy have been reported, but this risk may not receive enough consideration from clinicians. We describe four patients presenting with multiple SCC while receiving prolonged (two to three years) voriconazole therapy. Three patients had underwent lung transplantation. SCC were preceded by photosensitization lesions, and predominated in photoexposed area, particularly the face. Therapy associated surgery, chemotherapy in one case, and voriconazole discontinuation; replacement by posaconazole or itraconazole did not trigger other photosensitive lesions. Once voriconazole withdrawn, preneoplastic lesions regressed. In conclusion, prolonged voriconazole therapy may enhance the risk of photoinduced SCC in immunocompromised patients, and skin monitoring is mandatory.

[Non-fatal disseminated mucormycosis in a solid organ transplant]. / Mucormycose disséminée d'évolution favorable chez une greffée pulmonaire.

BACKGROUND: Mucormycosis is a rare fungal infection occurring most frequently in immunocompromised patients. The pathogens are filamentous fungi, order of Mucorales. Disseminated mucormycosis is a severe, life treating disease. Early diagnosis is a major determinant for prognosis, however, it remains difficult. The management consists in an early antifungal therapy using lipid formulation of amphotericin B associated with an extensive surgical debridement. Despite this therapeutic of choice, the mortality of disseminated mucormycosis remains high. OBSERVATION: We report the case of disseminated mucormycosis in a 25 years old woman 9 months after a pulmonary transplantation. The clinical presentation included pulmonary and thyroid localization and the pathogen was Absidia corymbifera. The patient survived thanks to a large surgical debridement, and an early antifungal bitherapy by lipid formulation of amphotericin B and posaconazole. CONCLUSION: The re-emergence and the high mortality of mucormycosis in solid organ transplant receiver show the necessity to find new therapeutic approaches. Posaconazole associated with liposomal amphotericin B could be an interesting option to treat disseminated mucormycosis and improve their outcome.

[Management of central sleep apnea]. / Conduite à tenir devant un syndrome d'apnées du sommeil central.

Central sleep apnea is highly prevalent in association with heart failure, some neurological diseases and chronic opioids use. There are two main categories of central sleep apnea respectively related with different underlying conditions. Some hypocapnic patients exhibit respiratory control system instability and central apnea occurs when PaCO(2) falls below the threshold for apnea during sleep. The other group are patients with chronic hypercapnia mainly in the context of neuromuscular disorders or obesity hypoventilation syndrome. All these patients should be assessed by recording blood gases, polysomnography and ventilatory responses to CO(2). Cardiologic assessment should include pro-brain natriuretic factor (pro-BNP) and cardiac echography whereas neurological examination requires brain imaging and/or electromyography. Ventilatory supports used for treating central sleep apnea are non-invasive ventilation and servo-assisted ventilation in hypercapnic and hypocapnic patients respectively.