BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)

Objective. To assess the clinical effects of rituximab therapy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods. The study group comprised 11 patients who had active AAV despite receiving maximally tolerated doses of cyclophosphamide or had contraindications for cyclophosphamide use. All patients had ANCA reactive against proteinase 3. The patients received rituximab infusions and glucocorticoids to induce remission. Three patients also received plasma exchange. No other immunosuppressive agents were used. Glucocorticoids were tapered as soon as control of disease activity was achieved. Disease activity was monitored using the Birmingham Vasculitis Activity Score, modified for Wegener's granulomatosis.Results. Rituximab therapy was well tolerated by all patients, and adverse events were rare. Following the rituximab infusions, circulating B lymphocytes became undetectable, and ANCA titers decreased significantly. Remission was achieved in all patients and was maintained while B lymphocytes were absent.Conclusion. The ability to achieve stable remissions with rituximab in patients with AAV refractory to conventional therapy suggests that B lymphocyte depletion may be a safe, effective, mechanism-based treatment modality for treatment of patients with these conditions.

Although the quality of evidence was low, the published literature since 2006 suggests that CHEST's 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017.

Objective. This study was conducted to evaluate the efficacy and safety of repeated and prolonged B cell depletion with rituximab (RTX) for the maintenance of long-term remission in patients with chronic relapsing granulomatosis with polyangiitis (Wegener's) (GPA).Methods. We conducted a single-center observational study of all patients with chronic relapsing GPA treated with at least 2 courses of RTX between Janu- Conclusion. RTX appeared to be effective and safe for the induction and maintenance of remission in patients with chronic relapsing GPA. Repeated depletion of B lymphocytes seems to be associated with a low risk of infections. Preemptive re-treatment decisions can be individualized based on serial B lymphocyte and PR3 ANCA monitoring. The use of RTX for the maintenance of long-term remission merits further formal investigation.

The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Miles Weinberger , MD ; and Richard S. Irwin , MD, Master FCCP ; on behalf of the CHEST Expert Cough Panel BACKGROUND:We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

on behalf of the CHEST Expert Cough PanelBronchopulmonary C-fi bers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human. [ Evidence-Based Medicine ]