The following represent additions to UpToDate since the last version of What’s New that were considered by the authors and editors to be of particular interest.
ASTHMA
Anti-interleukin-5 antibody — The safety and efficacy of the monoclonal anti-interleukin (IL)-5 antibody was assessed in a randomized trial of 106 patients with poorly-controlled eosinophilic asthma. Subjects received intravenous infusions of reslizumab or placebo for 12 weeks [1]. The reslizumab group had a greater reduction in sputum eosinophils and improved airflow obstruction, but only a trend toward improved asthma control as measured by the Asthma Control Questionnaire (ACQ). (See "Alternative and experimental agents for the treatment of asthma", section on 'Anti-IL-5 antibodies'.)
Proton pump inhibitor therapy in poorly controlled asthma — In a randomized trial, 306 children with poorly controlled asthma, but without symptoms of gastroesophageal reflux (GER), were randomly assigned to lansoprazole (weight-based dosing) or placebo for 24 weeks [2]. No differences in the asthma control questionnaire (ACQ) scores or lung function were noted between treatment groups. In a subset of 115 children with pH probe monitoring results, 49 (43 percent) had evidence of acidic reflux. No difference in asthma outcomes was noted in this subgroup, although the number of patients was small. Proton pump inhibitor therapy does not improve asthma outcomes in patients with poorly controlled asthma who do not have symptoms of GER. (See "Gastroesophageal reflux and asthma", section on 'Asymptomatic patients'.)
Long-acting beta agonists — The safety of long-acting beta agonists (LABAs) in asthma was examined in the most extensive meta-analysis to date, performed by the US Food and Drug Administration. An increased risk of serious asthma events (hospitalization, intubation, or death) was associated with LABA therapy in the overall population (60,954 patients), particularly among the youngest patients aged 4 to 11 years [3]. However, this increased risk was not seen in children and adolescents who also received inhaled glucocorticoids as an assigned study treatment. Conclusions regarding the protective effect of inhaled glucocorticoids are limited by the small number of patient events in this subgroup. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Meta-analysis and clinical trial data'.)
BRONCHIECTASIS
Ivacaftor for cystic fibrosis — The G551D mutation, which is present in about 5 percent of individuals with cystic fibrosis (CF), interferes with activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Ivacaftor (VX-770) is the first approved CF therapy that restores the functioning of a mutant CF protein and was specifically developed to overcome the defect in CFTR function caused by the G551D mutation. In a phase 3 trial, subjects with a G551D mutation treated with ivacaftor experienced an improvement in FEV1 compared with subjects treated with placebo [4]. In addition, ivacaftor reduced the frequency of pulmonary exacerbations and pulmonary symptoms, and resulted in a significant weight gain of 2.7 kg.
We recommend ivacaftor for all individuals with CF who carry at least one copy of the G551D mutation and are six years of age or older. Ivacaftor is given at a dose of 150 mg by mouth every 12 hours with fat-containing foods. All individuals with CF should undergo genotyping to determine whether they carry the G551D mutation. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'CFTR modulators'.)
COPD
Vitamin D and COPD exacerbations — High dose vitamin D supplementation did not reduce the incidence of exacerbations in patients with moderate to very severe COPD who were randomly assigned to take vitamin D 100,000 IU or placebo orally every four weeks for a year [5]. The median time to first exacerbation did not differ between the groups, nor did exacerbation rates, forced expiratory volume in one second (FEV1), hospitalization, quality of life, or death. However, the rate of exacerbations was reduced in patients with severe vitamin D deficiency (serum 25-[OH] D levels <10 ng/mL) at baseline. Further research is needed to validate this latter observation. (See "Management of acute exacerbations of chronic obstructive pulmonary disease", section on 'Prevention'.)
Longitudinal assessment of BODE index — The course of COPD is variable and difficult to predict. The BODE index incorporates measures of weight, airway obstruction, dyspnea, and exercise capacity. A longitudinal study followed 751 patients with COPD for a median of 64 months; a statistically significant increase (worsening) in the BODE index was noted in 14 percent [6]. Worsening of the BODE index was more likely to occur in patients with more severe obstruction at baseline. Concordance between changes in the BODE index and FEV1 was low, suggesting that the BODE index provides different prognostic information. (See "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions", section on 'BODE index'.)
CRITICAL CARE
Extracorporeal membrane oxygenation and neurological injury — Neurologic injury is considered uncommon among adult extracorporeal membrane oxygenation (ECMO) survivors. However, contrary to this belief, a prospective cohort study of 87 patients who received ECMO for more than 12 hours detected a neurological injury in approximately 50 percent of patients [7]. The types of neurological injury included coma of uncertain cause, encephalopathy, anoxic brain injury, stroke, brain death, and myoclonus. These findings may have been a consequence of the conditions that prompted ECMO, rather than a complication of the ECMO process. (See "Extracorporeal membrane oxygenation (ECMO) in adults", section on 'Neurological'.)
Dopamine in septic shock — Patients who receive dopamine during septic shock have increased mortality compared with patients who receive norepinephrine. This was demonstrated by a meta-analysis of six randomized trials (1408 patients) that compared dopamine with norepinephrine in septic shock [8]. Patients who received dopamine had a higher 28-day mortality rate than patients who received norepinephrine. Although the causes of death in the two groups were not compared, arrhythmic events were two times more common with dopamine than norepinephrine. The results indicate that norepinephrine is preferable to dopamine as a vasopressor in the management of septic shock. (See "Use of vasopressors and inotropes", section on 'Choice of agent in septic shock'.)
Initiation of enteral nutrition — Two strategies have been used to initiate enteral nutrition: incrementally increasing the infusion rate until the target maintenance rate is achieved or initiating the infusion at the target maintenance rate. The EDEN trial was a multicenter open-labelled trial that compared these approaches by randomly assigning 1000 mechanically ventilated patients with acute lung injury to receive either full enteral feeding or low-volume enteral feeding for six days, after which both groups received full enteral feeding [9]. The trial found no differences in the number of ventilator-free days, 60-day mortality, or the frequency of infectious complications. However, the low-volume feeding group had less vomiting, smaller gastric residual volumes, lower mean plasma glucose levels, and less constipation. These data suggest that initial low-volume enteral feeding has fewer undesirable effects than initial feeding at the target rate. (See "Nutrition support in critically ill patients: Enteral nutrition", section on 'Amount and rate'.)
Vasopressin and terlipressin in vasodilatory shock — Vasopressin and terlipressin are vasopressors used to manage vasodilatory shock (eg, septic shock). These agents reduce the need for alternative vasopressors, but do not appear to improve mortality. This was demonstrated by a meta-analysis of six randomized trials (512 patients), which found less need for norepinephrine but no improvement in short-term mortality among patients who received either vasopressin or terlipressin compared with placebo or supportive care [10]. (See "Use of vasopressors and inotropes", section on 'Vasopressin and analogs'.)
Parenteral nutrition as an adjunct to enteral nutrition — The use of parenteral nutrition as an adjunct to enteral nutrition to improve provision of calories and protein may be harmful according to two studies. The first study was a multicenter trial that randomly assigned 4640 critically ill adults who were already receiving enteral nutrition to have supplemental parenteral nutrition initiated early (within 48 hours of ICU admission) or late (after the eighth day of ICU admission) [11]. Those who received early parenteral nutrition were more likely to develop a new infection and had a longer duration of mechanical ventilation, ICU stay, and hospitalization. The second study was an observational study that compared three groups: enteral nutrition alone, enteral nutrition plus early parenteral nutrition, and enteral nutrition plus late parenteral nutrition [12]. Enteral nutrition plus either early or late parenteral nutrition was associated with increased mortality compared to enteral nutrition alone. (See "Nutrition support in critically ill patients: An overview", section on 'Parenteral nutrition'.)
INTERSTITIAL LUNG DISEASE
Gastroesophageal reflux and idiopathic pulmonary fibrosis — The association of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) was assessed in a systematic review that included 14 studies. Based on studies of ambulatory pH probe monitoring, it was noted that 67 to 76 percent of patients with IPF had abnormal distal esophageal acid exposure, although a causal relationship could not be determined [13]. Classic symptoms of GERD (heartburn, acid regurgitation) were poor predictors of increased esophageal acid exposure among patients with moderate to severe IPF. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Gastroesophageal reflux and chronic microaspiration'.)
The effect of treatment for gastroesophageal reflux disease (GERD) on progression of idiopathic pulmonary fibrosis (IPF) has been examined in a retrospective study. Among 204 patients with IPF, reported use of anti-GERD medications was associated with decreased radiographic fibrosis scores on chest computed tomography and was an independent predictor of longer survival time [14]. Additional data are needed before anti-GERD therapy becomes a routine part of management of IPF. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Gastroesophageal reflux and chronic microaspiration'.)
Prednisone, azathioprine, and n-acetylcysteine in idiopathic pulmonary fibrosis — The multicenter PANTHER trial (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF) is a three-armed trial comparing combination therapy (prednisone-azathioprine-N-acetylcysteine), N-acetylcysteine alone, and placebo [15]. In an interim analysis, combination therapy was associated with greater mortality (11 versus 1 percent), more hospitalizations (29 versus 8 percent), and more serious adverse events (31 versus 9 percent) than placebo. Therefore, the combination therapy arm of the trial was stopped; the N-acetylcysteine and placebo arms are ongoing. We suggest not initiating combination therapy (azathioprine, prednisone, N-acetylcysteine) in patients with IPF. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Prednisone-Azathioprine-N-Acetylcysteine'.)
INTERVENTIONAL PULMONOLOGY
Endobronchial ultrasound-guided transbronchial needle aspiration — Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) appears to be a reasonable substitute for mediastinoscopy in the appropriate clinical setting (ie, general anesthetic, rapid on-site cytology, different needles for each lymph node station). This was demonstrated by a prospective cohort study of 190 patients with potentially resectable lung cancer and small mediastinal lymph nodes that found no significant differences in the pathological lymph node stage when EBUS-TBNA was compared with mediastinoscopy [16]. The sensitivity, specificity, positive predictive value, and negative predictive value for EBUS-TBNA and mediastinoscopy were nearly identical for the two approaches. (See "Endobronchial ultrasound: Indications, advantages, and complications", section on 'Regional lymph nodes'.)
LUNG TRANSPLANTATION
Alpha-1 antitrypsin deficiency — The effect of lung transplantation for advanced emphysema due to alpha-1 antitrypsin (AAT) deficiency was examined in a retrospective case-control study [17]. The median survival of 83 patients with advanced emphysema due to AAT deficiency (PI*ZZ) was compared with that of 70 nontransplanted AAT deficient individuals of similar age, gender, smoking history and lung function. The median survival times were significantly longer among transplanted (11 years, 95% CI 9 to 14) versus nontransplanted (5 years, 95% CI 4 to 6) patients. (See "Treatment of alpha-1 antitrypsin deficiency", section on 'Lung and liver transplantation'.)
Obesity and lung transplantation — The role of obesity in the development of primary graft dysfunction (PGD) was examined in a prospective cohort study of lung transplantation for COPD or idiopathic pulmonary fibrosis (IPF). Among 512 adult lung transplant recipients, obesity was associated with a twofold increase in grade 3 PGD developing within 72 hours of transplantation [18]. It is hypothesized that higher levels of proinflammatory adipokines (eg, leptin) may contribute to systemic inflammation and thus to PGD. (See "Lung transplantation: General guidelines for recipient selection", section on 'Nutritional status'.)
PULMONARY VASCULAR DISEASE
Treatment guidelines for acute pulmonary embolism — The ninth edition of the American College of Chest Physicians’ Clinical Practice Guidelines on Antithrombotic Therapy and Prevention of Thrombosis has been released. Key changes in the management of acute pulmonary embolism (PE) include stratification of the decision to initiate empiric anticoagulant therapy according to the degree of clinical suspicion, increased acceptance of subcutaneous fondaparinux as primary therapy, and stratification of the duration of anticoagulant therapy on the basis of bleeding risk [19]. (See "Anticoagulation in acute pulmonary embolism" and "Treatment of acute pulmonary embolism" and "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".)
Rivaroxaban for acute pulmonary embolism — Rivaroxaban is an oral factor Xa inhibitor that is administered as a fixed dose and does not require laboratory monitoring. A trial randomly assigned 4832 patients with symptomatic acute PE to receive either rivaroxaban or standard anticoagulant therapy [20]. There was no difference in the incidence of recurrent venous thromboembolism, but there was less major bleeding in the rivaroxaban group. These results indicate that rivaroxaban therapy may be beneficial in patients with acute PE; however, confirmation is needed before rivaroxaban becomes routine therapy. (See "Anticoagulation in acute pulmonary embolism", section on 'Rivaroxaban'.)
Catheter-directed thrombolysis of iliofemoral deep vein thrombosis — Thrombolytic therapy decreases the incidence of postthrombotic syndrome among patients with lower extremity deep vein thrombosis (DVT). This was illustrated by a trial that randomly assigned 209 patients with iliofemoral DVT to receive either thrombolytic therapy followed by anticoagulant therapy or anticoagulant therapy alone [21]. There was less postthrombotic syndrome at two years among patients who received thrombolytic therapy, but this came at a cost of increased bleeding. (See "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis", section on 'Lower extremity deep vein thrombosis'.)
Pulmonary hypertension and pulmonary Langerhans cell histiocytosis — Pulmonary hypertension (PH) complicating pulmonary Langerhans cell histiocytosis (PLCH) has a poor prognosis and the optimal treatment is not known. In a series of 12 patients with PH and PLCH, use of therapies for pulmonary arterial hypertension (ie, endothelin receptor antagonist, a phosphodiesterase 5 inhibitor, iloprost, or a combination) led to modest improvements in mean pulmonary arterial pressure and pulmonary vascular resistance between baseline and follow up evaluations [22]. No significant worsening of oxygenation was observed with treatment. (See "Pulmonary Langerhans cell histiocytosis", section on 'Treatment'.)
Prognosis of pulmonary hypertension — The one-year survival of patients newly diagnosed with pulmonary arterial hypertension (PAH) can be predicted using a risk score derived from the Registry to Evaluate Early and Long-term PAH Disease Management (the REVEAL registry). This risk score was validated by a prospective cohort study of 504 patients that found that a risk score of 1 to 7, 8, 9, 10 to 11, and ≥12 correlated with one-year survival of 95, 92, 89, 72, and 66 percent, respectively [23]. Calculation of the risk score is described separately. (See "Overview of pulmonary hypertension", section on 'Prognosis'.)
Saddle pulmonary embolism — A saddle PE is a PE that has lodged at the bifurcation of the main pulmonary artery. The hemodynamic consequences of saddle PE and their response to therapy are similar to other types of acute PE. This was demonstrated by a retrospective study of 680 patients with PE, which included 37 patients with saddle PE [24]. Among the patients with saddle PE, transient hypotension occurred in 14 percent, persistent shock occurred in 8 percent, and in-hospital mortality occurred in 5 percent. (See "Overview of acute pulmonary embolism", section on 'Definitions'.)
Sildenafil for pulmonary arterial hypertension — Sildenafil improves pulmonary hemodynamics and exercise capacity in patients with PAH. The long term effects of sildenafil were demonstrated by an uncontrolled, open-label, three-year extension of the SUPER-1 trial, called the SUPER-2 trial [25]. The SUPER-2 trial included 259 patients and found persistent improvement in the six-minute walk distance and World Health Organization (WHO) functional class in 46 and 29 percent of patients, respectively. The estimated three year survival rate was 79 percent. (See "Treatment of pulmonary hypertension", section on 'PDE5 inhibitors'.)
Endothelin receptor antagonists, gender, and race — There is some evidence that the magnitude of the response to endothelin receptor antagonists in PAH may vary according to gender and race. An observational study of 1130 patients that used data extracted from randomized trials found that women had significantly greater improvement in their six-minute walk test than men (+29.7 m) and white individuals had a trend toward greater improvement in their six-minute walk test than black individuals (+43.6 m) [26]. (See "Treatment of pulmonary hypertension", section on 'Endothelin receptor antagonists'.)
Pulmonary thromboendarterectomy and mortality — Perioperative mortality among patients undergoing pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH) has decreased. This was illustrated by an observational study from an international registry that reported an in-hospital postoperative mortality rate of 4.7 percent between 2007 and 2009 [27], which is a lower mortality rate than historical controls. (See "Chronic thromboembolic pulmonary hypertension: Surgical treatment", section on 'Outcomes following pulmonary thromboendarterectomy'.)
SLEEP MEDICINE
Continuous positive airway pressure and the metabolic syndrome — There is evidence that positive airway pressure therapy improves the metabolic syndrome associated with obstructive sleep apnea (OSA). This was demonstrated by a trial that randomly assigned 90 patients with OSA (mean apnea hypopnea index of 48 events per hour of sleep) and excessive daytime sleepiness to receive either therapeutic continuous positive airway pressure (CPAP) or sham CPAP for three months, followed by a one month washout period and then crossover to the other intervention [28]. Compared with patients who received sham CPAP, those who received therapeutic CPAP had a significantly greater decreases in their body mass index, subcutaneous fat, and mean serum total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and glycated hemoglobin. (See "Management of obstructive sleep apnea in adults", section on 'Outcomes'.)
Sleep-related breathing disorders and myocardial infarction — Myocardial infarction is associated with worsening sleep-related breathing disorders. This was demonstrated by a prospective cohort study of 2721 individuals without known cardiovascular disease who were followed for a mean of five years [29]. Fifty seven subjects (2 percent) had a myocardial infarction during the study. The adjusted apnea hypopnea index increased a mean of 6.4 respiratory events per hour of sleep among those who had a myocardial infarction, compared with only 2.7 respiratory events per hour of sleep among those who had not had a myocardial infarction. (See "Cardiovascular effects of obstructive sleep apnea", section on 'Coronary artery disease'.)
Adherence with continuous positive airway pressure — One night without CPAP is enough to mitigate the benefits of CPAP therapy in patients with OSA. The sensitivity of patients to discontinuation of CPAP was illustrated by a trial that included 41 patients with OSA who had been using CPAP successfully for at least one year [30]. After only four nights without CPAP, the frequency of oxyhemoglobin desaturation events increased during sleep, indicating recurrence of OSA. The patients were then randomly assigned to a CPAP withdrawal group (ie, subtherapeutic CPAP) or a CPAP group (ie, therapeutic CPAP) for two weeks. CPAP withdrawal led to recurrence of abnormal respiratory events within one night, increased morning and evening blood pressure within two weeks, and increased morning heart rate within two weeks. Subjective daytime sleepiness also increased within two weeks. CPAP withdrawal was not associated with deterioration of psychomotor performance. (See "Adherence with continuous positive airway pressure (CPAP)", section on 'Consequences'.)
Exercise for obstructive sleep apnea — Exercise may modestly improve OSA even in the absence of significant weight loss. This was suggested by a trial that randomly assigned 43 patients with OSA to undergo exercise training (intervention) or a stretching program (control) for 12 weeks [31]. The exercise program consisted of 150 minutes per week of moderate intensity aerobic exercise performed four days per week. The aerobic exercise was followed by resistance training two days per week. Patients in the exercise training group had a reduction in their apnea hypopnea index (from 32.2 to 24.6 events per hour of sleep) despite no change in body weight. In contrast, patients in the stretching group did not have any improvement in their apnea hypopnea index. (See "Management of obstructive sleep apnea in adults", section on 'Exercise'.)
Sleep-related breathing disorders and occupational errors — Although most research has focused on the impact of sleep-related breathing disorders on driving performance, occupational errors are also more common among individuals with sleep-related breathing disorders. This was illustrated by a prospective cohort study of 4957 police officers, of whom 40 percent screened positive for at least one sleep disorder (mostly OSA) [32]. Patients who screened positive for any sleep disorder were more likely to make an administrative error at work, to fall asleep while driving, to commit an error or safety violation due to fatigue, to exhibit uncontrolled anger toward suspects, to be absent from work, or to fall asleep during meetings. (See "Performance and safety risks of sleep deprivation and sleep disorders", section on 'Sleep related breathing disorders'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
Searching for
