Rituximab for auto-immune alveolar proteinosis, a real life cohort study.

BACKGROUND: Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody. METHODS: We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed. RESULTS: Thirteen patients were included. No patients showed improvement 6 months after treatment, but, 4 patients (30%) presented a significant decrease of alveolar-arterial difference in oxygen after 1 year. One patient received lung transplantation and one patient was lost of follow-up within one year. Although a spontaneous improvement cannot be excluded in these 4 patients, improvement was more frequent in patients naïve to prior specific therapy and with higher level of anti-GM-CSF antibodies evaluated by ELISA. No serious adverse event was evidenced. CONCLUSIONS: These data do not support rituximab as a second line therapy for patients with refractory aPAP.

Unusual evolution in Wegener's granulomatosis: recovery of pulmonary involvement while renal disease progressed to end-stage.

A 54-year-old male patient was admitted for acute respiratory distress with fever. He was suffering from chronic sinusitis/rhinitis and had persistent otitis for the past 2 months before admission despite several antibiotics courses. He developed a complex pulmonary involvement (embolism and diffuse alveolar hemorrhage) with acute glomerular disease (proteinuria and hematuria but initially no renal failure). Clinical suspicion of Wegener's granulomatosis was confirmed by the positive high titer of antineutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and despite a negative nasal biopsy. Treatment including cyclophosphamide and methylprednisolone intravenous pulses permitted pulmonary recovery over 4 weeks contrasting with the development of rapidly progressive glomerulonephritis and polyneuropathy of lower limbs. Renal biopsy showed pauci-immune crescentic and necrotizing glomerulonephritis. However, despite additional plasma exchanges, acute kidney injury worsened and the patient ended up in dialysis. Such a dissociated evolution was unexpected in this case since pulmonary and renal involvements reflected the same pathological process (small vessels vasculitis/capillaritis) and the same pathogenic mechanism (antiproteinase 3 autoantibodies).

CPAP treatment supported by telemedicine does not improve blood pressure in high cardiovascular risk OSA patients: a randomized, controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with hypertension, which is one of the intermediary mechanisms leading to increased cardiovascular morbidity. This study aimed at evaluating the effects of a combination of continuous positive airway pressure (CPAP) and telemedicine support on blood pressure (BP) reduction in high cardiovascular risk OSA patients. DESIGN: A multi-center randomized controlled trial that compared standard CPAP care and CPAP care and a telemedicine intervention. SETTING: Sleep clinics in France. PATIENTS OR PARTICIPANTS: 107 adult (18-65 years old) OSA patients (AHI > 15 events/h) with a high cardiovascular risk (cardiovascular SCORE > 5% or secondary prevention). INTERVENTIONS: Patients were randomized to either standard care CPAP (n = 53) or CPAP and telemedicine (n = 54). Patients assigned to telemedicine were equipped with a smartphone for uploading BP measurements, CPAP adherence, sleepiness, and quality of life data; in return, they received pictograms containing health-related messages. MEASUREMENTS: The main outcome was home self-measured BP and secondary outcomes were cardiovascular risk evolution, objective physical activity, CPAP adherence, sleepiness and quality of life. RESULTS: Self-measured BP did not improve in either group (telemedicine or standard care). Patients in primary prevention showed greater BP reduction with CPAP treatment than those in secondary prevention. CONCLUSIONS: CPAP treatment supported by telemedicine alone did not improve blood pressure and cardiovascular risk in high cardiovascular risk OSA patients. This study emphasizes the need for diet and physical activity training programs in addition to CPAP when aiming at decreasing cardiometabolic risk factors in these patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01226641.

Low physical activity is a determinant for elevated blood pressure in high cardiovascular risk obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity, including hypertension. Beyond the severity of nocturnal hypoxia, other factors such as metabolic abnormalities but also sedentary behaviors and insufficient physical activity may contribute to elevated blood pressure (BP). To clarify the respective role of these factors as determinants of BP in OSA patients, we examined the relationship between BP and anthropometrics, severity of sleep apnea, and objectively measured physical activity and sedentary behaviors. METHODS: Ninety-five adults presenting with OSA (apnea-hypopnea index > 10 events/h) and high cardiovascular risk (63.3 ± 8.8 y; body mass index: 29.9 ± 4.9 kg/m(2); apnea-hypopnea index: 41.3 ± 17.5/h; cardiovascular risk score: 13.5 ± 3.7%) were included. Physical activity and sedentary behaviors were objectively assessed by actigraphy, and self-measured home BP monitoring was measured. Logistic regression models adjusted for sex, age, and body mass index were built to identify the predictors of self-measured morning and evening BP. RESULTS: Physical activity was significantly related to obesity but not to the severity of sleep apnea or sleepiness. Sedentary behaviors were associated with self-measured morning and evening systolic BP (r = 0.32, P = .002; r = 0.29, P = .004). Steps per day were inversely associated with evening BP (r = -0.27, P = .01). Univariate analysis identified steps/d and time spent in vigorous physical activity as determinants for evening self-measured BP. In multivariate analysis, only steps/d were identified as a significant determinant of evening BP. CONCLUSIONS: Physical activity is the major determinant for evening BP in adults with OSA presenting high cardiovascular risk. Our results emphasize the need for lifestyle counseling programs in combination with CPAP to encourage regular physical activity in OSA subjects to obtain better BP control. (ClinicalTrials.gov registration NCT01226641.)