Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial.

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.

Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies.

Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo. St George's Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo. No safety signals were identified from adverse-event or other safety data. Once-daily olodaterol 5 µg and 10 µg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile.

Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a common lung disease leading to progressive decline in lung function. Inhibition of release of inflammatory mediators by p38 inhibitors may be a useful treatment for chronic inflammation of the airways thought to underlie the pathogenesis of the disease. OBJECTIVES: To evaluate the efficacy and safety of PH-797804, a potent and selective p38 inhibitor, in adults with moderate to severe COPD (Global Initiative for Chronic Obstructive Lung Disease stage II/III). METHODS: This was a randomised, adaptive design, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were initially randomised to placebo, 0.5, 3, 6 or 10 mg PH-797804 once daily and treated for 6 weeks following a 2-week run-in. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) compared with placebo after 6 weeks of treatment. Secondary endpoints included other spirometric parameters, transition dyspnoea index, rescue mediation use, high sensitivity C-reactive protein and symptoms. A total of 230 patients were assigned to treatment; placebo (n=45), 0.5 mg (n=20), 3 mg (n=47), 6 mg (n=70) and 10 mg (n=48). PH-797804 showed a statistically significant improvement in trough FEV1 at week 6 compared with placebo of 0.086 litre (95% Bayesian CI 0.008 to 0.164) and 0.093 litre (95% CI 0.018 to 0·166) at 3 and 6 mg PH-797804, respectively. PH-797804 3 mg and 6 mg showed an improvement in the baseline dyspnoea index/transition dyspnoea index total focal score at week 6. PH-797804 was well tolerated at all doses studied. CONCLUSIONS: PH-797804 demonstrated improvements over placebo in lung function parameters and dyspnoea in patients with moderate to severe COPD. TRIALREGNO: NCT00559910.

Traqueobroncopatía osteocondroplástica: presentación simulando asma / Tracheobronchopathia osteochondroplastica. Clinical presentation mimicking asthma

La traqueobroncopatía osteocondroplástica (TO) (o traqueopatía osteocondroplástica otraqueopatía osteoplástica)1 es una entidad rara de etiopatogenia desconocida caracterizada por múltiples nódulos de cartílago o hueso originados en el tejido cartilaginoso de la vía aérea, que se proyectan dentro de la luz traqueobronquial. Generalmente decurso crónico y benigno, es casi siempre un hallazgo; cuando presenta síntomas estos son inespecíficos y se deben al estrechamiento de la vía aérea, al engrosamiento de la pared traqueobronquial, o a alguna complicación. Al ser poco reconocida favorece los errores diagnósticos. Reportamos un caso sintomático de TO, confundida con asma, que además presentaba rinosinusitis crónica e infecciones recurrentes de la vía aérea alta y baja. Además de presentar este caso con gran afectación y progresión hasta bronquios distales, mostramos otros 2 presuntos casos sin confirmación endoscópica.

The tracheobronchopathia osteochondroplastica (TO) is a rare disease of unknown pathogenesis. It is characterized by multiple osteocartilaginous nodules protrudinginto the tracheobronchial airway lumen. Generally it is an incidental finding because its evolution is chronic and benign; when symptoms are present, they are non specific and result from the obstruction of the airway, the thickening of the tracheobronchial wall or some complication. Since it is an uncommon condition the diagnostic errors arefrequent. We report a symptomatic TO case, that was misdiagnosed as asthma, and in addition the patient had chronic sinusitis and recurrent upper and lower respiratory tract infections. This case had progressive invasion of distal bronchi. We also report two other suspected cases without endoscopic confirmation.

Traqueobroncopatía osteocondroplástica: presentación simulando asma / Tracheobronchopathia osteochondroplastica. Clinical presentation mimicking asthma

La traqueobroncopatía osteocondroplástica (TO) (o traqueopatía osteocondroplástica otraqueopatía osteoplástica)1 es una entidad rara de etiopatogenia desconocida caracterizada por múltiples nódulos de cartílago o hueso originados en el tejido cartilaginoso de la vía aérea, que se proyectan dentro de la luz traqueobronquial. Generalmente decurso crónico y benigno, es casi siempre un hallazgo; cuando presenta síntomas estos son inespecíficos y se deben al estrechamiento de la vía aérea, al engrosamiento de la pared traqueobronquial, o a alguna complicación. Al ser poco reconocida favorece los errores diagnósticos. Reportamos un caso sintomático de TO, confundida con asma, que además presentaba rinosinusitis crónica e infecciones recurrentes de la vía aérea alta y baja. Además de presentar este caso con gran afectación y progresión hasta bronquios distales, mostramos otros 2 presuntos casos sin confirmación endoscópica. (AU)

The tracheobronchopathia osteochondroplastica (TO) is a rare disease of unknown pathogenesis. It is characterized by multiple osteocartilaginous nodules protrudinginto the tracheobronchial airway lumen. Generally it is an incidental finding because its evolution is chronic and benign; when symptoms are present, they are non specific and result from the obstruction of the airway, the thickening of the tracheobronchial wall or some complication. Since it is an uncommon condition the diagnostic errors arefrequent. We report a symptomatic TO case, that was misdiagnosed as asthma, and in addition the patient had chronic sinusitis and recurrent upper and lower respiratory tract infections. This case had progressive invasion of distal bronchi. We also report two other suspected cases without endoscopic confirmation. (AU)

Ruptura bronquial: Manejo inicial con la colocación de un stent endobronquial / The bronchial rupture: Initial management with the placement of an endobronchial stent

La ruptura bronquial es una condición rara y grave, secundaria a un traumatismo severo del tórax. Presenta una alta morbimortalidad y la mayoría de las veces requiere resolución quirúrgica. Presentamos un caso que, no habiendo sido diagnosticado inicialmente como tal, padeció complicaciones que dilataron el tratamiento correspondiente. Se realizó la colocación de stent endobronquial y sucesivas fibrobroncoscopías de control y aspiración, además de kinesia respiratoria y drenaje postural, evolucionando favorablemente.

The bronchial rupture is a rare and serious condition, secondary to a severe thoracic trauma. It often requires surgical treatment and the case fatality is high. In the case presented here the treatment was delayed because of late diagnosis and complications. The therapeutic measures included endobronchial stenting, successive control and aspiration fiberbronchoscopies, kinetic respiratory assistance and postural drainage. The evolution was favorable.

Ruptura bronquial: Manejo inicial con la colocación de un stent endobronquial / The bronchial rupture: Initial management with the placement of an endobronchial stent

La ruptura bronquial es una condición rara y grave, secundaria a un traumatismo severo del tórax. Presenta una alta morbimortalidad y la mayoría de las veces requiere resolución quirúrgica. Presentamos un caso que, no habiendo sido diagnosticado inicialmente como tal, padeció complicaciones que dilataron el tratamiento correspondiente. Se realizó la colocación de stent endobronquial y sucesivas fibrobroncoscopías de control y aspiración, además de kinesia respiratoria y drenaje postural, evolucionando favorablemente. (AU)

The bronchial rupture is a rare and serious condition, secondary to a severe thoracic trauma. It often requires surgical treatment and the case fatality is high. In the case presented here the treatment was delayed because of late diagnosis and complications. The therapeutic measures included endobronchial stenting, successive control and aspiration fiberbronchoscopies, kinetic respiratory assistance and postural drainage. The evolution was favorable. (AU)

Efficacy of oral telithromycin in community-acquired pneumonia caused by resistant Streptococcus pneumoniae.

The efficacy of oral telithromycin 800mg once daily for 7 days was evaluated in a multicentre, multinational study in patients with community-acquired pneumonia caused by Streptococcus pneumoniae resistant to penicillin and/or erythromycin. Per-protocol clinical and bacteriological outcomes were assessed 10-17 days post-therapy. Of the 129 patients with S. pneumoniae infection, 16 were infected with strains resistant to penicillin and/or erythromycin. Fifteen of these 16 patients (93.8%) were assessed as clinically and bacteriologically cured at the post-therapy visit.