Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking. RESEARCH QUESTION: Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections. METHODS: We conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data. RESULTS: We included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7-6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardia spp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316-1591) vs 580 (200-1190), p=0.01). Nine patients had died (9%), but only one death was related to infection. INTERPRETATION: Patients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.

Evolution and Predictive Factors of Improvement of Obstructive Sleep Apnea in an Obese Population After Bariatric Surgery.

STUDY OBJECTIVES: Our objectives were to determine in an obese population (body mass index > 35 kg/m²) the number of patients, after gastric bypass (GBP), who no longer met French Ministry of Health criteria for utilizing positive airway pressure (PAP), and the predictive factors of obstructive sleep apnea (OSA) improvement. METHODS: Between June 2012 and August 2014 we diagnosed OSA in 129 incident patients requiring PAP therapy before GBP. A postoperative sleep recording was undertaken for 44 of these patients after a weight loss of at least 10%. RESULTS: Most of the patients showed severe OSA with a mean [standard deviation] apnea-hypopnea index (AHI) of 52.8 [23.8] events/h. The body mass index was 46.1 [5.1] kg/m². All the patients were treated via PAP and most of them via auto-titrating PAP with a range of 4-16 cmH2O. Following the GBP, in 31 patients (70.5%) OSA was improved, allowing PAP to be stopped (AHI < 15 events/h). The Epworth Sleepiness Scale score, the modified Medical Research Council dyspnea scale, the loudness of snoring, and sleep structure were improved. AHI was decreased by a mean of 40.9 [22.4] events/h (P < .001). In a multivariate logistic regression model, age (P = .018) and sleep oxygen desaturation index (P = .049) appeared to predict improvement of OSA. CONCLUSIONS: After GBP, 70.5% of the patients no longer met French Ministry of Health criteria for utilizing PAP, allowing discontinuation of this treatment. At diagnosis, a younger age and a less severe sleep oxygen desaturation were predictive factors of this improvement.

[Impact of COPD: from disability to exacerbations]. / Impact de la BPCO: du handicap aux exacerbations.

COPD is a common disease characterized by health status impairment and disability that is usually progressive. Exacerbations of COPD, an acute event in the course of the disease, have effects on symptoms and patient's quality of life. Assessment of symptoms and risk of exacerbations is useful to guide strategy management of the disease. COPD disability includes different aspects. Its assessment needs to consider the classification of severity of airflow limitation, symptoms, comorbidities and impairment of patient's health-related quality of life. The rate at which exacerbations occur varies between patients. History of previous exacerbations and severity of airflow limitation are the best predictors of the frequency and severity of exacerbations. Severity of the symptoms is associated with an increased risk of exacerbations. Exacerbations increase deterioration in health status and leads to severe disability, inducing a vicious circle from disability to exacerbations. At an individual patient level, an understanding of the impact of COPD requires to assess the patient's disability, the risk of future exacerbations, and the identification of comorbidities.

Better outcome of patients undergoing enteral tube feeding after myeloablative conditioning for allogeneic stem cell transplantation.

BACKGROUND: Parenteral nutrition (PN) is still widely preferred to enteral nutrition (EN) in malnourished patients undergoing allogeneic stem-cell transplantation (allo-SCT) after myeloablative conditioning (MAC). The purpose was to determine whether EN improves early outcome after MAC allo-SCT. METHODS: Early outcome was prospectively assessed in patients undergoing MAC allo-SCT. A total of 121 consecutive patients undergoing a first MAC allo-SCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative syndrome were included. Patients who received cord blood were excluded. Enteral nutrition was systematically offered, although PN was provided when EN had been refused or was poorly tolerated. Among the patients, 94 received EN (EN group) and 27 did not (non-EN group). Overall survival (OS), cumulative incidence of engraftment and acute graft-versus-host disease (aGVHD) within the first 100 days after transplantation were studied. Because EN and PN treatment assignments were not random, propensity score adjustments were performed on patient outcomes. RESULTS: Outcome was better in the EN group than in the non-EN group for OS (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04-0.42; P=0.0008), neutrophil (HR, 2.07; 95% CI, 1.26-3.39; P=0.004), and platelet (HR, 1.93; 95% CI, 1.004-3.70; P=0.049) engraftments and aGVHD development (HR, 0.12; 95% CI, 0.04-0.39; P=0.0004). In Cox model analysis, EN demonstrated a protective effect (HR, 0.20; 95% CI, 0.05-0.77; P=0.019) on OS, whereas demonstrated a detrimental impact (HR, 4.18; 95% CI, 1.02-17.12; P=0.047). Enteral nutrition was found to be an independent factor in neutrophil engraftment (HR, 2.17; 95% CI, 1.24-3.81; P=0.007), whereas PN delayed platelet engraftment (HR, 0.57; 95% CI, 0.33-0.99; P=0.046). Enteral nutrition was the only factor that was protective against grades 3 to 4 aGVHD development (HR, 0.19; 95% CI, 0.05-0.72; P=0.01). CONCLUSIONS: Routine use of EN is preferable to upfront PN in these patients.

[From COPD to chronic respiratory failure]. / De la BPCO a l'insuffisance respiratoire chronique.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow obstruction, leading to an airflow limitation that is not fully reversible, with extrapulmonary effects or comorbidities that may contribute to the severity of the disease. The most important cause is tobacco smoking that is associated with an abnormal inflammatory pulmonary and systemic response. Chronic airflow obstruction is defined by postbronchodilator FEV1/FVC ratio < 0.7. A spirometric classification of the COPD severity is recommended into four stages. COPD has a variable natural history. Usually, COPD is a progressive disease with an increase in airways obstruction. Airflow limitation leads to hyperinflation, the most important cause of dyspnea in COPD patients. Assessment of the prognosis is based on the severity of the spirometric abnormality (FEV1) and includes other factors such as body mass index (BMI), dyspnea and exercise impairment. The underlying disease process in COPD leads to gas exchange abnormalities, chronic respiratory insufficiency and pulmonary hypertension. The more frequent causes of death are respiratory insufficiency, cardiovascular comorbidities and lung cancer.

[Acute exacerbations of chronic obstructive pulmonary disease]. / Exacerbations de bronchopneumopathie chronique obstructive.

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is defined by modification of the usual COPD symptoms, dyspnea, coughing and sputum, beyond daily variations, with a sudden onset, and requiring modification of the usual treatment. Exacerbations stud the course of COPD. Their frequency is variable, averaging 1-2 per year. Their frequency generally increases with COPD severity. Exacerbations impair patients' quality of life and aggravate disease prognosis by accelerating the decline in FEV1, the primary indicator of respiratory function. The most frequent causes of exacerbations are viral and bacterial respiratory infections and pollution. No cause is identified for nearly one third of all exacerbations. Most exacerbations can be treated at home, if a careful search for signs of clinical severity is negative. Treatment combines inhaled bronchodilator agents (beta-2 agonists, combined if necessary with anticholinergics) and oral corticosteroid therapy (prednisone: 0.5 mg/kg/d for 1 week) when the COPD is severe or signs of severity accompany the exacerbation. Antibiotic therapy is justified when the sputum appears purulent. Severe exacerbation may require oxygen therapy in cases of severe hypoxemia (PaO(2)<60 mm Hg) or mechanically assisted ventilation, essentially by noninvasive ventilation in cases of respiratory acidosis (pH<7.35). Noninvasive ventilation improves dyspnea and respiratory acidosis, diminishes respiratory frequency, intubation, duration of hospitalization, nosocomial infections, and mortality. Pulmonary follow-up is necessary after an exacerbation, especially to prevent the recurrence of exacerbations by measures that have been demonstrated to be effective, including help in smoking cessation, adaptation of COPD treatment, vaccination against influenza and pneumonia (pneumococci), and respiratory rehabilitation. Early diagnosis and rapid treatment of exacerbations can limit their impact, improve quality of life, and reduce the risk of hospitalization.