American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2020
Randomized Controlled TrialOmalizumab for Aspirin-Hypersensitivity and Leukotriene Overproduction in Aspirin-Exacerbated Respiratory Disease: A Randomized Trial.
Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. ⋯ The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001). Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
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The stepwise approach to pharmacological treatment in adult asthma mandates that asthma treatment is progressively stepped up to achieve symptom control and reduce the risk of exacerbations and stepped down after a period of prolonged control. This review proposes that in adults without good asthma control, well-controlled asthma can only be achieved in approximately 70% of patients across the strata of severity, and only if there is a progressive increase in inhaled corticosteroid/long-acting β2 agonist therapy to a maintenance inhaled corticosteroid dose that causes the same magnitude of systemic side effects as oral prednisone at a 5-mg daily dose. ⋯ Finally, it is widely assumed that asthma symptom control equates to elimination of risk of asthma attacks, an assumption that may not apply to many patients, particularly those with more severe asthma. We propose that further research be undertaken to determine the optimal levels of asthma control and the potential value of different treatment targets, such as control of type-2 airway inflammation, that can be achieved with currently available treatment, based on efficacy, side effects, and cost.
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Am. J. Respir. Crit. Care Med. · Jun 2020
Observational StudyPleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions.
Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery. ⋯ Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76). Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.
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Am. J. Respir. Crit. Care Med. · Jun 2020
Randomized Controlled TrialReduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in COPD Patients.
Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information. Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data. ⋯ For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient's COPD. Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.