Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

Idiopathic pulmonary fibrosis diagnosed concomitantly with diffuse squamous cell lung cancer on surgical lung biopsy: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is a disease with a poor prognosis and has been associated with increased lung cancer incidence. CASE PRESENTATION: We report the case of a Caucasian 75-year-old woman, a former smoker, hospitalized for breathlessness with a chest computed tomography scan showing an interstitial lung disease. A surgical lung biopsy was performed, confirming a pattern of usual interstitial pneumonia but also numerous disseminated foci of well-differentiated focally invasive squamous cell carcinoma without hypermetabolic lung nodule, mass, or enlarged lymph node visualized on chest computed tomography or positron emission tomography scan. Nintedanib was started for its antifibrotic and antitumor properties, without any other antineoplastic treatment. Three years after initiation of nintedanib, clinical, functional, and computed tomography scan evaluations were stable, and there was no evidence for evolution of the squamous cell carcinoma. CONCLUSIONS: Data are scarce regarding the benefit of nintedanib in patients with idiopathic pulmonary fibrosis-associated lung cancer, and it is unclear whether nintedanib could have a preventive role in lung carcinogenesis in idiopathic pulmonary fibrosis patients. This experience could help the scientific community in case of similar incidental findings.

[Ambulatory management of bilateral secondary spontaneous pneumothorax in palliative care]. / Prise en charge palliative ambulatoire d'un pneumothorax spontané secondaire bilatéral.

INTRODUCTION: Secondary spontaneous pneumothoraces account for 35% of all pneumothoraces after the age of 50. Their management is still debated and can be challenging due to the underlying respiratory condition. In our observation, the use of small-bore chest tubes allowed prolonged ambulatory care in a palliative setting. CASE REPORT: We report the case of a 54-year-old woman suffering from a leiomyosarcoma with multiple pulmonary metastases who had repeated episodes of pneumothorax, one of which was bilateral. Treatment involved the bilateral insertion of 8.5F pigtail catheters connected to Heimlich valves that allowed management as an outpatient. Recurrences were treated similarly, in association with oncological management, providing great additional benefits for patient comfort in this palliative context. CONCLUSION: Altogether, this case report confirms the applicability of outpatient management for drained spontaneous secondary pneumothoraces, even bilateral, especially in a palliative-care setting.

[Hypersensitivity Pneumonitis: An update]. / Mise au point : pneumopathies d'hypersensibilité.

Hypersensitivity Pneumonitis (HP) is a common immune-mediated interstitial lung disease (ILD) induced by repeated exposure to environmental antigens in susceptible individuals. The most commonly known forms are bird fancier's disease and farmer's lung. However, the antigens involved are widely diverse. Therefore, the list of causes of HP is frequently expanding. HP seems to be under-diagnosed owing to its highly heterogeneous presentation in both the non-fibrotic and fibrotic subtypes and could represent up to 15% of all ILDs encountered in clinical practice. However, the recognition of HP cases is essential to ensure appropriate therapy for the patient. Home health care workers' intervention is sometimes critical in this context. In case of confirmed exposure, the diagnosis could be considered with high confidence if the high-resolution computed tomography (HR-CT) shows a typical HP pattern associated with a lymphocytosis over 30% in the broncho-alveolar lavage (BAL). In all other situations, the patients should undergo further investigations and additional histopathological sampling should be considered and submitted to a multidisciplinary team discussion. After diagnosis, antigenic eviction is the rule whenever possible. Corticosteroid treatment is the first-line medical treatment for severe forms and aims to prevent the development of fibrosis. Anti-fibrotic therapy is now an option for patients with progressive ILD and failure of immunomodulatory/immunosuppressive therapies.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

Idiopathic pulmonary fibrosis: Significance of the usual interstitial pneumonia (UIP) CT-scan patterns defined in new international guidelines.

INTRODUCTION: The new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns: probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear. METHODS: We used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of≥10% in forced vital capacity (FVC), or hospitalization. RESULTS: Of the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] =3.12 [1.24; 7.83], P=0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI]=2.85[1.00; 8.10], P=0.049). CONCLUSION: The majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF.

[Lung metastases of pancreatic adenocarcinoma: Watch for the second train!] / Adénocarcinome pancréatique métastatique aux poumons : un train peut en cacher un autre !

Pulmonary metastases due to a pancreatic cancer are difficult to diagnose and demonstrate a wide range of radiological patterns. We report the case of a 37-year-old female patient, without past medical history, with multicystic lung disease in a context of chronic abdominal pain, fatigue and weight loss. After several months of diagnostic delay, pathological examination of surgical lung biopsies led to the diagnosis of secondary deposits of pancreatic cancer. The clinical and radiogical situation deteriorated quickly with the development of alveolar consolidation and Aspergillus superinfection was then diagnosed. This case illustrates the value of an early decision to undertake surgical lung biopsy in the work-up of multicystic lung disease when cancer is suspected. In addition, in the specific context of cancer, faced with clinical and/or radiological deterioration, it is essential to look for infection, particularly aspergillosis.

[Hypersensitivity pneumonitis presenting as acute respiratory distress syndrome]. / Pneumopathie d'hypersensibilité révélée par un syndrome de détresse respiratoire aiguë.

INTRODUCTION: Hypersensitivity pneumonitis (HP) are typically subacute in their presentation and the diagnosis may be difficult. METHOD: We report a case of a hypersensitivity pneumonitis in a 27-years-old woman, caused by exposure to mould in an insalubrious mobile home. The initial presentation was with acute respiratory distress syndrome complicating RSV pneumonia, treated with ribavirin and corticosteroids in winter 2013-2014. The diagnosis of hypersensitivity pneumonitis was based on clinical and radiological relapse occurring during winter 2014-2015 with confirmed exposure to antigen with fungal sampling at home, respiratory deterioration with antigen rechallenge and a compatible chest CT-scan. CONCLUSION: The diagnosis of hypersensitivity pneumonitis should be considered in similar cases. Treatment is based mainly on removing exposure to the causative antigen.

[Spontaneous lung volume reduction following pneumonia in a patient with emphysema]. / Normalisation ventilatoire après réduction de volume pulmonaire naturelle consécutive à une infection pulmonaire.

INTRODUCTION: Lung volume reduction can be effective in appropriately selected patients with severe emphysema and is associated with reduced breathlessness and improved survival. Spontaneous resolution of emphysematous bullae can also sometimes occur. CASE REPORT: We report a case of severe smoking-related emphysema in a 60-year-old patient, who presented in October 2013 with a right upper lobe acute community-acquired pneumonia on the background of previously undocumented emphysema. The patient improved following treatment with co-amoxiclav and serial radiology showed progressive cicatricial retraction. Nine months later there had been a major functional improvement characterized by a complete normalization of the patient's ventilatory parameters, specifically a 45% improvement in FEV1. In the literature, the average FEV1 improvement obtained by surgical or endoscopic lung volume reduction techniques does not exceed 28%. CONCLUSION: Rarely, emphysematous bullae resolve following infections. Further studies of the mechanisms involved in these natural regressions may be of interest in the development of new therapeutics.

[Features distinguishing ornithosis from avian acute hypersensitivity pneumonitis - a retrospective analysis]. / Pneumopathies et exposition aux oiseaux : ornithose ou pneumopathie d'hypersensibilité aiguë aviaire ?

INTRODUCTION: The aim of our study was to compare the features at diagnosis in patients with ornithosis to patients with avian acute hypersensitivity pneumonitis (HP). Clinical, biological and radiological differences could potentially help clinicians to distinguish these diseases. METHODS: We conducted a retrospective study on patients admitted from 2000 to 2016 in three hospitals. Ornithosis was diagnosed based on a positive polymerase chain reaction for Chlamydophila psittaci on respiratory samples and/or a seroconversion while HP was diagnosed on the basis of at least one positive serum precipitin. RESULTS: Twelve patients with HP and 13 patients with ornithosis were identified. Compared to HP, ornithosis occurred more frequently in males (P=0.047), with less previous respiratory diseases (P=0.01), shorter symptom duration (P=0.03), less frequently bilateral crackles (P=0.004), more severe disease requiring more frequently intensive care admission (P=0.005), higher CRP values (P=0.005) and more profound lymphopenia (P=0.02). Ground glass shadowing on CT scan (P=0.001) or bronchiectasis (P=0.03) were more frequently noted in patients with HP. CONCLUSIONS: Our results suggest that patients with ornithosis and HP have important differences in their clinical, biological, and radiological presentation.

[Interstitial lung disease and pancreatic cancer: Series of two cases]. / Pneumopathie infiltrante diffuse et cancer du pancréas : présentation de deux cas.

INTRODUCTION: Pancreatic cancer is often not diagnosed until at a metastatic stage at which point the prognosis is very poor. Pulmonary metastases are pleomorphic, often present at the time of diagnosis and can lead to the discovery of an asymptomatic primary disease. CASE REPORT: We describe two cases aged 60 and 74 years, where imaging identified what was thought to be an interstitial lung disease but which was actually metastasis from pancreatic cancer. In the first case, CT showed multiple excavated pulmonary nodules but the presentation with medullary compression led rapidly to pathological diagnosis on bone lesions. In the second patient, a history of rheumatoid arthritis and the lack of abdominal symptoms led to an initial search for disease related to the rheumatoid disease. Histopathology, from lung and bone biopsies, enabled a correct diagnosis to be achieved. CONCLUSION: Where atypical interstitial lung disease occurs, biopsy should be considered in order not to delay a diagnosis of cancer, especially pancreatic cancer.

[Pulmonary nocardiosis with cerebral abscesses mimicking metastatic lung cancer: Three cases and a review of literature]. / Nocardiose pulmonaire avec abcès cérébraux mimant un cancer bronchique métastatique : trois cas et revue de la littérature.

Nocardiosis is an infectious disease with wide range of clinical features, which can eventually lead to death. The agent responsible belongs to the genus Nocardia that includes about fifty different species. Nocardiosis occurs mainly in immunocompromised hosts. We report here three cases of disseminated nocardiosis misdiagnosed initially as cerebral metastatic lung cancer. These patients, including two immunocompetent hosts, presented with both pulmonary and cerebral lesions. In all three patients, the diagnosis was based on magnetic resonance imaging with diffusion sequence, apparent diffusion coefficient reconstruction and neurosurgical cerebral biopsies. Treatment with an appropriate antibiotic regimen was prolonged for several months. Progress was favorable with full resolution of the neurological symptoms and the radiological abnormalities. These three cases emphasize the diagnostic challenge of nocardiosis, especially in disseminated disease.

[Plasmapheresis failure in the treatment of auto-immune pulmonary alveolar proteinosis]. / Échec de plasmaphérèse dans une protéinose alvéolaire pulmonaire auto-immune.

INTRODUCTION: Auto-immune pulmonary alveolar proteinosis is a rare disorder characterized by the accumulation of surfactant proteins in the alveoli. CASE REPORT: We report a case of a 41-year-old smoker, presenting initially with acute respiratory failure. Whole lung lavages were effective initially but only for a few weeks. GM-CSF subcutaneous injections were not effective, and then plasmapheresis were tried. CONCLUSION: This is the fifth report of the use of this treatment in auto-immune pulmonary alveolar proteinosis. Plasmapheresis was not effective in our patient.

[The management of complicated parapneumonic effusions in France]. / Prise en charge des épanchements parapneumoniques compliqués : état des lieux des pratiques en France.

INTRODUCTION: There are no French guidelines for the management of complicated parapneumonic effusions. A national observational study was carried out to assess the main features of current clinical practice for this condition. MATERIAL AND METHODS: A questionnaire was sent by email to the 1500 members of the Société de Pneumologie de Langue Française (SPLF) between 15th November and 15th December 2012. RESULTS: There were 92 responders, i.e. a response rate of 6%. Of these, 87 physicians mentioned that they were involved in the management of patients with complicated parapneumonic effusions with a median number of cases of 10 per year (IQR: 5-20). Chest tube drainage was the main approach used for pleural fluid aspiration (n=51/87), followed by repeated thoracentesis (n=29/87) and early surgery (1/87). Five physicians answered both chest tube drainage or repeated thoracentesis and one physician either chest tube drainage or early surgery. Pleural fibrinolytics were never used by 20% of physicians, only in case of loculations by 70% and by 10% of respondents in all cases. Only 3 physicians combined fibrinolytics with DNAse. A double antibiotic dose was used by one third of physicians. All the physicians used respiratory physiotherapy during hospitalization and to aid recovery. Follow-up practices were heterogeneous. CONCLUSIONS: The management of complicated parapneumonic effusions varies significantly in France. National guidelines may be helpful to define best practice and aid in its implementation.

[Parapneumonic pleural effusions: Epidemiology, diagnosis, classification and management]. / Les épanchements pleuraux parapneumoniques: épidémiologie, diagnostic, classification, traitement.

Parapneumonic pleural effusions represent the main cause of pleural infections. Their incidence is constantly increasing. Although by definition they are considered to be a "parapneumonic" phenomenon, the microbial epidemiology of these effusions differs from pneumonia with a higher prevalence of anaerobic bacteria. The first thoracentesis is the most important diagnostic stage because it allows for a distinction between complicated and non-complicated parapneumonic effusions. Only complicated parapneumonic effusions need to be drained. Therapeutic evacuation modalities include repeated therapeutic thoracentesis, chest tube drainage or thoracic surgery. The choice of the first-line evacuation treatment is still controversial and there are few prospective controlled studies. The effectiveness of fibrinolytic agents is not established except when they are combined with DNase. Antibiotics are mandatory; they should be initiated as quickly as possible and should be active against anaerobic bacteria except for in the context of pneumococcal infections. There are few data on the use of chest physiotherapy, which remains widely used. Mortality is still high and is influenced by underlying comorbidities.

[Pulmonary alveolar proteinosis]. / La protéinose alvéolaire pulmonaire.

Alveolar proteinosis (AP) is a rare disease characterized by alveolar accumulation of surfactant components, which impairs gas exchange. AP is classified into three groups: auto-immune AP defined by the presence of plasma autoantibodies anti-GM-CSF, the most frequent form (90% of all AP); secondary AP, mainly occurring as a consequence of haematological diseases, or following on from toxic inhalation or infections, and genetic AP, which affects almost exclusively children. AP diagnosis is suspected where chest CT-scan demonstrates interstitial lung disease with a crazy paving aspect; and confirmed by bronchoalveolar lavage, which has a milky appearance and contains periodic acid Schiff positive proteinaceous alveolar deposits. The use of surgical lung biopsy to confirm AP is less frequent nowadays. In this context, positive antibodies against GM-CSF indicates an auto-immune etiology of the AP. Concerning management, whole lung lavage is the gold standard therapy. In refractory AP, new treatments are available such as subcutaneous or inhaled GM-CSF supplementation, or rituximab infusions. The clinical course is unpredictable. Spontaneous improvement or even cure can occur, and the 5-year actuarial survival is 95%. The most frequent complications are infectious etiology.