Find Print
0 Find synonyms

Find synonyms Find exact match

What's new in pulmonary and critical care medicine
Official reprint from UpToDate® ©2016 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
What's new in pulmonary and critical care medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2016. | This topic last updated: Oct 18, 2016.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Safety of inhaled glucocorticoid-LABA combination therapy in asthma (September 2016)

In early studies, a small increase in asthma-related deaths associated with salmeterol led the US Food and Drug Administration to place a boxed warning on the use of long-acting beta agonists (LABAs) in asthma. While concerning, the number of events was small, and it could not be determined if the potential risk of salmeterol could be mitigated by combining LABAs with inhaled glucocorticoids. Three large randomized trials including 30,000 children and adults found no increase in asthma-related adverse events or deaths among patients who used combination inhalers with salmeterol or formoterol plus an inhaled glucocorticoid versus glucocorticoid monotherapy [1-3]. These studies support the safety of these fixed-dose combination inhalers in patients with moderate-to-severe asthma. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Potential risk mitigation'.)

Farm animals, asthma, and the innate immune response (September 2016)

Exposure to farm animals, particularly early in life, is negatively associated with the development of allergic disease. A recent study compared 60 children from Amish and Hutterite communities, two genetically similar, reproductively isolated farming populations in the United States [4]. The Amish have traditional, single-family farms with exposure to horses and dairy cows, whereas the Hutterites live and work on large farms that are highly industrialized. Amish children have significantly lower rates of asthma and allergic sensitization than their Hutterite counterparts. Endotoxin levels were significantly higher in the Amish homes, and dust extracts from the Amish homes, but not the Hutterite homes, significantly blocked airway hyperresponsiveness and eosinophilia in a mouse model. In addition, in vitro studies showed an enhanced innate immune response in Amish, but not Hutterite, children. These findings suggest that the closer contact with farm animals in the Amish lifestyle may help prevent the development of asthma by altering the innate immune response. (See "Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors", section on 'Farms, villages, worms, and other parasites'.)

Lack of association between acetaminophen and asthma in children (September 2016)

More frequent use of acetaminophen was associated with increased asthma-related complications in children in observational studies, leading to the recommendation by some for children with asthma to avoid acetaminophen. However, these findings were not replicated in a prospective, randomized trial comparing acetaminophen and ibuprofen use [5]. In this trial, 300 children with mild persistent asthma were randomly assigned to as-needed treatment with acetaminophen or ibuprofen for fever or pain over a 48-week period. All children received standard controller therapy for asthma. There was no significant difference between the two groups in the number of asthma exacerbations requiring treatment with systemic glucocorticoids or in the number of asthma exacerbations. Thus, we do not advise restricting the use of acetaminophen in children with asthma. (See "Virus-induced wheezing and asthma: An overview", section on 'Acetaminophen use for febrile illnesses'.)

Evaluation of recurrent wheezing in children <2 years of age (August 2016)

The American Thoracic Society has developed guidelines for evaluation of children <2 years of age who have recurrent wheezing that is unresponsive to bronchodilators or inhaled or systemic glucocorticoids [6]. Suggested evaluation includes one or more of the following: videofluoroscopic swallowing study (modified barium swallow) for possible swallowing dysfunction; 24-hour esophageal pH monitoring for assessment of gastroesophageal reflux; and/or flexible fiberoptic bronchoscopy bronchoalveolar lavage (BAL) to assess for lower airway bacterial infection. Our approach is consistent with these guidelines. (See "Approach to wheezing in infants and children", section on 'Radiography' and "Approach to wheezing in infants and children", section on 'Endoscopy' and "Approach to wheezing in infants and children", section on 'Evaluation for gastroesophageal reflux'.)

Omalizumab for allergic asthma in children 6 to 11 years of age (July 2016)

Omalizumab, a monoclonal antibody to immunoglobulin E (IgE), is an option for patients with moderate to severe persistent asthma and sensitization to perennial aeroallergens who are inadequately controlled on inhaled glucocorticoids. The US Food and Drug Administration (FDA) has now lowered the approved age range from 12 to 6 years of age, expanding the therapeutic options in step 5 asthma management in children [7]. (See "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Step-up therapy' and "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications", section on 'Anti-IgE therapy' and "Anti-IgE therapy", section on 'Omalizumab therapy in asthma'.)

House dust mite sublingual immunotherapy for allergic asthma (May 2016)

Injection allergen immunotherapy with house dust mite extract has demonstrated benefit in patients with asthma and house dust mite allergy, but is inconvenient and carries a small risk of serious allergic reactions. Sublingual immunotherapy tablets (SLIT-tablets) are a safer form of allergen immunotherapy with proven efficacy in allergic rhinoconjunctivitis, but studies in patients with allergic asthma are limited. In a randomized trial of over 800 house dust mite-sensitive adults with asthma not controlled by inhaled budesonide and short-acting beta-agonists, subjects were treated with house dust mite SLIT-tablets or placebo for 7 to 12 months, after which inhaled budesonide was gradually withdrawn and then stopped [8]. House dust mite SLIT significantly prolonged the time to first moderate or severe asthma exacerbation, reducing the absolute risk of an exacerbation during budesonide withdrawal from 32 to 25 percent with placebo and SLIT, respectively. However, clinically meaningful improvements in other measures of asthma symptoms were not clearly demonstrated. Thus, further study is needed to assess the effectiveness of SLIT-tablets in patients with allergic asthma. HDM SLIT-tablets are not yet available in the United States, but are available in Australia, Japan, and parts of Europe. (See "Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma", section on 'Moderate-persistent asthma'.)


Glycopyrronium-indacaterol versus fluticasone-salmeterol for moderate-to-severe COPD (June 2016)

Current guidelines suggest use of an inhaled glucocorticoid (ICS)-long-acting beta agonist (LABA) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at increased risk of exacerbations. New data suggest that long-acting anticholinergic (LAMA)-LABA combinations, which improve pulmonary function and variably reduce symptoms in patients with COPD at low risk of exacerbations, may also benefit patients at increased risk of exacerbation. In a multicenter trial, glycopyrronium-indacaterol once daily was compared with fluticasone-salmeterol twice daily in over 3000 patients with moderate-to-severe COPD and at least one moderate-severe exacerbation in the previous year [9]. Over the 52-week trial, glycopyrronium-indacaterol reduced exacerbations by 11 percent and was associated with slightly fewer episodes of pneumonia compared with fluticasone-salmeterol. The use of LAMA-LABA combinations in these patients, in preference to an ICS-LABA combination, requires further study to determine the generalizability and durability of these findings. (See "Management of stable chronic obstructive pulmonary disease", section on 'Comparison with LAMA-LABA'.)

Combination inhaled glucocorticoid/long-acting beta agonists in patients with COPD and cardiovascular risk factors or disease (May 2016)

While the evidence has been generally reassuring about the safety of combination inhaled glucocorticoid plus long-acting beta agonist (ICS-LABA) inhalers in patients with chronic obstructive pulmonary disease (COPD), patients with known cardiovascular disease (CVD) were excluded from previous clinical trials. In the three-year randomized trial, Study to Understand Mortality and MorbidITy (SUMMIT), the effect of the fluticasone furoate-vilanterol combination inhaler was compared with the individual components and placebo in almost 17,000 patients with moderate COPD (FEV1 between 50 and 70 percent of predicted) and known or increased risk of CVD [10]. Relative to placebo, the combination inhaler did not affect all-cause mortality or composite cardiovascular events. Thus, the presence of CVD should not affect the role of ICS-LABA inhalers in COPD. (See "Management of the patient with severe COPD and cardiovascular disease", section on 'Combination inhaled bronchodilator plus glucocorticoid'.)


Corticosteroids not beneficial in severe sepsis without shock (October 2016)

The administration of corticosteroids to patients with sepsis is generally reserved for those with septic shock. A recent randomized trial of nearly 400 adults examined the efficacy of corticosteroids in patients with severe sepsis who did not have shock [11]. Compared with placebo, an infusion of hydrocortisone (200 mg daily for five days followed by tapering until day 11) had no effect on mortality or progression to shock. This trial supports our current recommendation that corticosteroids not be routinely administered to septic patients without shock. (See "Glucocorticoid therapy in septic shock", section on 'HYPRESS'.)

Oxygenation goals in critically ill patients (October 2016)

The optimal level of oxygenation in mechanically ventilated patients is unknown. A recent randomized trial reported that, compared with a conventional approach to oxygenation (partial arterial pressure of oxygen [PaO2] up to 150 mmHg or peripheral arterial oxygen saturation [SpO2] 97 to 100 percent), a conservative approach (PaO2 70 to 100 mmHg or SpO2 94 to 98 percent) resulted in lower mortality and fewer episodes of shock, liver failure, and bacteremia [12]. However, these preliminary results should be confirmed by a larger multicenter trial before a conservative approach to oxygenation should be routinely adopted for mechanically ventilated patients. (See "Overview of mechanical ventilation", section on 'Fraction of inspired oxygen'.)

Early mobilization in critically ill patients (July 2016, Modified October 2016)

Two recent trials on the role of physical therapy for early mobilization of critically ill patients report conflicting outcomes:

One trial of mechanically ventilated surgical intensive care unit (ICU) patients reported that compared with usual care, implementation of a rigid goal-directed early mobilization strategy resulted in improved mobilization scores, decreased ICU length of stay, improved functional mobility at hospital discharge, and possibly improved mortality [13].

A single-center trial of 300 critically ill ventilated patients reported no benefit for an intensive daily physical rehabilitation regimen initiated in the ICU and continued until hospital discharge, when compared with usual care (ie, intervention as needed when requested by the health care team) [14].

Findings from the trial reporting benefit may be more reliable, because the communication loop that was in place ensured that patients actually received the physical therapy intervention. Nonetheless, these findings need to be replicated before early mobilization can be routinely recommended. (See "Post-intensive care syndrome (PICS)", section on 'Prevention'.)

IDSA/ATS guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia (August 2016)

The Infectious Diseases Society of America and the American Thoracic Society have released updated guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) [15]. Empiric therapy for HAP (algorithm 1) and VAP (algorithm 2) should include agents with activity against Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli. Choice of a specific regimen for empiric therapy should be based upon knowledge of the prevailing pathogens (and susceptibility patterns) within the healthcare setting as well as risk factors for multidrug resistance in the individual patient. The guidelines emphasize that a seven-day course of antimicrobial therapy is appropriate for most patients rather than a longer duration. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Treatment'.)

Palliative care consultation for families of patients in the intensive care unit (August 2016)

Post-intensive care syndrome-family (PICS-F) is a term given to family members who have been affected physically and psychologically during the intensive care unit (ICU) stay of critically ill patients. Therapeutic measures for PICS-F are poorly studied. One multicenter randomized trial examined the impact of a palliative care-led consultation for surrogate decision-makers of critically ill patients in the ICU who were unlikely to wean from mechanical ventilation [16]. Compared with routine family meetings conducted by the ICU team, palliative care-led consultation did not reduce symptoms of anxiety or depression of family members and may have increased symptoms of posttraumatic stress disorder. However, limitations of this study include possible inadequate "dosing" of the intervention (on average, 1.4 encounters per family and physician presence at only 9 percent of meetings), leaving the possibility that more aggressive and supportive interventions may have different outcomes. (See "Post-intensive care syndrome (PICS)", section on 'Post-intensive care syndrome-family'.)

Aspirin does not prevent acute respiratory distress syndrome in adults (July 2016)

Preclinical and clinical observational studies have suggested a potential role for aspirin in the prevention of acute respiratory distress syndrome (ARDS). The ability of aspirin to prevent ARDS was tested in a randomized trial of 390 patients who were assessed upon presentation to an emergency department to be at risk of developing ARDS [17]. Aspirin, administered at 325 mg orally followed by 81 mg daily for seven days, had no effect on the incidence of ARDS at one week (approximately 10 percent in each group). However, the lower than expected rate of ARDS in this study may have limited the potential to detect a study drug effect. (See "Acute respiratory distress syndrome: Novel therapies in adults", section on 'Aspirin'.)

Outbreak of Burkholderia cepacia infection associated with contaminated oral liquid docusate (June 2016)

In June 2016, a multistate outbreak of Burkholderia cepacia infection was reported in the United States [18]. B. cepacia typically causes lung colonization and infection in patients with cystic fibrosis (CF), but most cases in this outbreak have involved mechanically ventilated intensive care unit patients without CF. The types of infections involved have not yet been reported. Because cases in one state have been associated with contaminated oral liquid docusate, the United States Centers for Disease Control and Prevention (CDC) recommends that facilities not use liquid docusate products for any patient. PharmaTech LLC, the manufacturer of the contaminated product, Diocto Liquid, has voluntarily recalled all non-expired lots [19]. Updated information about the outbreak and public health reporting can be found on the CDC’s website. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Outbreak of Burkholderia cepacia infection'.)

Apneic oxygenation in adults undergoing rapid sequence intubation in the emergency department (June 2016)

A number of techniques are used to prevent oxygen desaturation during rapid sequence intubation (RSI). One such technique involves giving oxygen passively via nasal cannula during the apneic phase of RSI. The results of a recent observational study of 635 patients being intubated in the emergency department suggest that this technique may have benefits beyond simply preventing hypoxia [20]. According to this study, the rate of first pass successful intubation without hypoxia was greater in patients managed with apneic oxygenation (82 percent) compared with patients managed without this intervention (69 percent). The improvement was due to both an increase in the rate of first pass successful intubation and a decrease in the incidence of hypoxia. While further studies are needed to confirm this finding, apneic oxygenation is a simple, beneficial intervention that should be used whenever RSI is performed in the emergency department. (See "Rapid sequence intubation for adults outside the operating room", section on 'Preoxygenation'.)

Dosing of direct oral anticoagulants in obese patients (June 2016)

Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject [21]. The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)

Early initiation of renal replacement therapy (June 2016)

It is unclear if the early initiation of renal replacement therapy (RRT) (ie, without an obvious indication such as severe hyperkalemia, metabolic acidosis, pulmonary edema or advanced uremic symptoms) provides any benefit to critically ill patients with acute kidney injury (AKI) compared with later initiations of RRT. Two new randomized trials have evaluated this in somewhat different patient populations. In the larger trial, 620 critically ill patients with severe AKI were randomized to early or delayed RRT [22]. There was no difference in 60-day mortality, and nearly one-half of patients in the delayed RRT group recovered without requiring RRT. In contrast, a second trial of 231 critically ill patients with more moderate AKI showed reduced 90-day mortality with earlier RRT [23]. In the delayed initiation group, only 11 patients ended up not requiring RRT, and early RRT reduced the duration of AKI and length of stay. However, we have lower confidence in the results of the smaller trial, because it is possible that the relatively small size of the trial resulted in an overestimate of the treatment benefit. It is otherwise difficult to understand how minor differences in the protocols and patient populations could achieve such dramatically different outcomes. Until further data are available, UpToDate suggests that RRT not be initiated in the absence of obvious clinical indications. (See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Timing of elective initiation'.)

Helmet-delivered noninvasive ventilation in acute respiratory distress syndrome (May 2016)

In patients with acute respiratory distress syndrome (ARDS), noninvasive ventilation (NIV) delivered with a face mask is often not sufficient to prevent intubation. Problems include patient discomfort and air leaks. Delivery of NIV using a helmet (ie, a transparent hood that covers the entire head, sealed with a rubber collar at the neck) may circumvent some of these issues. A preliminary trial compared the two approaches by randomly assigning patients with ARDS who required NIV to continue face mask NIV or switch to helmet–delivered NIV [24]. Helmet-delivered NIV reduced the need for intubation (18 versus 62 percent) and increased ventilator-free days. It also reduced length of stay and 90-day mortality without additional adverse effects. While encouraging, early trial termination may have exaggerated the efficacy. In addition, general concerns regarding limited physician experience and unclear guidelines regarding patient selection, optimal ventilator settings, and monitoring need to be addressed before helmet-delivered NIV can be applied as a therapy for patients with ARDS. (See "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Invasive versus noninvasive'.)

Simplified approach to acetylcysteine infusion for acetaminophen poisoning (April 2016)

The treatment of acetaminophen poisoning with acetylcysteine is sometimes complicated by nonallergic anaphylactic reactions (NAARs). The results of a large retrospective study, in addition to recent clinical experience, suggest that these reactions can be reduced by using a two-bag regimen instead of the traditional three-bag regimen described in the manufacturer’s package insert and most dosing references. In the study, NAARs occurred in 10 percent of the 389 patients treated with the standard regimen versus 4.3 percent of the 210 patients treated with a modified two-bag regimen [25]. In both regimens, acetylcysteine was infused over 20 hours. While further study is needed to ensure the safety and effectiveness of this regimen, we believe this is a reasonable approach to treatment in adults and older adolescents with acetaminophen poisoning. (See "Acetaminophen (paracetamol) poisoning in adults: Treatment", section on 'Simplified 20 hour IV protocol'.)


Revised criteria for acute exacerbations of idiopathic pulmonary fibrosis (August 2016)

An international working group has published a comprehensive review of acute exacerbations of idiopathic pulmonary fibrosis (IPF) that includes a revised definition and diagnostic criteria. The report defines an acute exacerbation of IPF as, "an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality" [26]. The following diagnostic criteria are suggested: a previous or concurrent diagnosis of IPF; acute worsening or development of dyspnea typically within one month of presentation; high-resolution computed tomography with new bilateral ground-glass abnormality and/or consolidation superimposed on usual interstitial pneumonia (eg, bibasilar reticular opacities associated with honeycomb changes and traction bronchiectasis); deterioration not fully explained by cardiac failure or fluid overload. Previous criteria required exclusion of other causes of acute deterioration, such as infection or pulmonary embolism. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Definition'.)

Screening for bleomycin-induced lung disease (June 2016)

There has been no consensus as to the utility of serial pulmonary function tests (PFTs, including the diffusing capacity for carbon monoxide [DLCO]) to detect early signs of bleomycin-induced lung disease, and practice is variable. Data reported from the contemporary Danish Testicular Cancer database suggest that a systematic approach to assessing PFTs before and during therapy, with early discontinuation of bleomycin for those with a drop in the DLCO of 25 percent or more, resulted in very low rates of both acute and chronic lung disease, and no adverse effect on oncologic outcomes [27]. We suggest assessment of PFTs, including DLCO, at baseline prior to treatment and at intervals during therapy for most adults receiving a bleomycin-containing chemotherapy regimen for any malignancy. The optimal frequency of testing is not established. We suggest discontinuation of bleomycin if there is a decrease in the DLCO of 25 percent or more, even if asymptomatic. (See "Bleomycin-induced lung injury", section on 'Screening for lung toxicity'.)

Danazol in telomere disorders (May 2016)

Telomeres are regions at the ends of chromosomes that maintain chromosomal integrity. Telomeres shorten with normal aging, but inherited disorders of premature telomere shortening can cause aplastic anemia (AA), pulmonary fibrosis, and certain malignancies. To date, no therapies have been developed to reverse premature telomere shortening. In the first prospective study to evaluate androgen therapy for telomere disorders, the androgen danazol was administered to 27 individuals with mutations that affect telomere length (most with AA) [28]. Danazol was associated with improved hematologic parameters in those with cytopenias, stabilization of pulmonary status in those with pulmonary fibrosis, and reduced telomere shortening in all evaluable participants. Androgens are an attractive candidate for treating telomere disorders, although further study is needed. (See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis", section on 'Telomerase mutations and telomere length' and "Pathogenesis of idiopathic pulmonary fibrosis", section on 'Genetic predisposition'.)

Possible delayed response to pirfenidone therapy in idiopathic pulmonary fibrosis (May 2016)

In patients with idiopathic pulmonary fibrosis (IPF), serial measurement of forced vital capacity (FVC) demonstrates substantial variability over time, making it difficult to analyze treatment responses and select subsequent treatment. In a follow-up to the original trials of pirfenidone in IPF, 34 subjects on pirfenidone and 68 subjects on placebo who experienced a ≥10 percent decline in FVC in the first three or six months were reassessed six months later [29]. Fewer subjects in the pirfenidone group experienced a further ≥10 percent decline in FVC or death in the following six months compared with the placebo group (2/34 versus 19/68, respectively). While the numbers are small, this study suggests that continuing pirfenidone may be of benefit despite initial evidence of disease progression. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Pirfenidone'.)


CPAP in obstructive sleep apnea does not reduce cardiovascular events (August 2016)

Whether continuous positive airway pressure (CPAP) therapy can reduce the increased risk of cardiovascular morbidity and mortality associated with obstructive sleep apnea (OSA) is unknown. The largest trial to address this issue randomized 2717 patients with moderate to severe OSA and established cardiovascular disease to CPAP therapy plus usual care or usual care alone (eg, education, risk factor modification) and followed patients for 3.7 years [30]. Despite adequate control of OSA, there was no difference in cardiovascular events (eg, cardiovascular deaths, myocardial infarction, or stroke). However, the exclusion of patients who are among the most likely to benefit from CPAP (eg, patients with “sleepy” OSA) and a low adherence rate to therapy (mean was 3.3 hours per night) may have limited the potential benefit from this therapy. While the cardiovascular benefits are unproven, CPAP should be administered for the associated noncardiovascular benefits (eg, improvement in symptoms and quality of life) and should remain the mainstay of therapy for patients with moderate to severe OSA. (See "Obstructive sleep apnea and cardiovascular disease", section on 'Cardiovascular events'.)

Chronic sleep-wake disturbances after traumatic brain injury (July 2016)

Sleep-wake disturbances are very common in the weeks to months following traumatic brain injury (TBI), and a new study suggests that many of these symptoms persist long term. In a prospective case-control study in which 31 patients with TBI of any severity were evaluated at 18 months after injury, 67 percent of patients had evidence of excessive daytime sleepiness on objective testing, compared with only 19 percent of healthy controls [31]. Patients also had persistent pleiosomnia (increased need for sleep), requiring an average of one more hour of sleep per 24 hours than controls. As in earlier studies, patients tended to underestimate their symptoms, emphasizing the importance of both subjective and objective sleep testing in patients with sleep-wake complaints after TBI. (See "Sleep-wake disorders in patients with traumatic brain injury", section on 'Natural history'.)

Prevalence of central sleep apnea in the community (July 2016)

Central sleep apnea (CSA) occurs with increased frequency in patients with heart failure and other comorbid cardiovascular diseases, but the prevalence in the general population has not been well established. In a population-based study of over 5000 community-dwelling adults age 40 years and older who underwent polysomnography, the prevalence of CSA was 0.9 percent [32]. By comparison, obstructive sleep apnea was present in 48 percent of patients. Risks factors for CSA included age older than 65 years, male gender, and self-reported heart failure. Cheyne-Stokes breathing was present in approximately half of patients with CSA. (See "Central sleep apnea: Risk factors, clinical presentation, and diagnosis", section on 'Epidemiology'.)

Clinical practice guideline for chronic insomnia in adults (May 2016)

The American College of Physicians has released a new clinical practice guideline for the management of chronic insomnia in adults [33]. The guideline recommends that all patients receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder. The guideline suggests that clinicians use a shared decision-making approach, including discussion of benefits, harms, and costs of short-term use of medications, to decide whether to add medication to CBT-I in patients with persistent symptoms. This approach is consistent with our preference for behavioral therapy over medication in most patients with chronic insomnia, particularly in older adults and patients with organ dysfunction, who are at increased risk for side effects from sedative-hypnotic drugs. (See "Treatment of insomnia", section on 'General approach'.)


IDSA guidelines on the management of aspergillosis (July 2016)

The Infectious Diseases Society of America released updated guidelines for the treatment of aspergillosis [34,35]. Voriconazole remains the mainstay of therapy for invasive aspergillosis. In contrast with the previous version of the guidelines, the updated version suggests consideration of combination therapy with voriconazole plus an echinocandin for initial therapy of severe invasive aspergillosis, particularly in patients with hematologic malignancy and/or in those with profound and persistent neutropenia. We generally agree with these guidelines and suggest combination therapy with voriconazole plus an echinocandin for patients with severe, microbiologically documented invasive aspergillosis, but we also consider combination therapy for all patients with an immunocompromising condition that led to disease. (See "Treatment and prevention of invasive aspergillosis", section on 'Guidelines'.)

Restriction of fluoroquinolone use in uncomplicated infections (May 2016)

The US Food and Drug Administration (FDA) has stated that the serious adverse effects associated with fluoroquinolones generally outweigh the benefits for patients with uncomplicated acute sinusitis, acute bronchitis, and urinary tract infections who have other treatment options [36]. For patients with these infections, fluoroquinolones should be reserved for those who have no alternative treatment options. This announcement was based on an FDA safety review showing that systemic fluoroquinolone use is associated with disabling and potentially permanent serious side effects, including those involving the tendons, muscles, joints, nerves, and central nervous system. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)

Use of UpToDate is subject to the Subscription and License Agreement.


  1. Stempel DA, Raphiou IH, Kral KM, et al. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. N Engl J Med 2016; 374:1822.
  2. Stempel DA, Szefler SJ, Pedersen S, et al. Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma. N Engl J Med 2016; 375:840.
  3. Peters SP, Bleecker ER, Canonica GW, et al. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N Engl J Med 2016; 375:850.
  4. Stein MM, Hrusch CL, Gozdz J, et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med 2016; 375:411.
  5. Sheehan WJ, Mauger DT, Paul IM, et al. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med 2016; 375:619.
  6. Official American Thoracic Society Clinical Practice Guidelines: Diagnostic Evaluation of Infants with Recurrent or Persistent Wheezing.
  7. Omalizumab. (Accessed on July 13, 2016).
  8. Virchow JC, Backer V, Kuna P, et al. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial. JAMA 2016; 315:1715.
  9. Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med 2016; 374:2222.
  10. Vestbo J, Anderson JA, Brook RD, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 2016; 387:1817.
  11. Keh D, Trips E, Marx G, et al. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA 2016.
  12. Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA 2016.
  13. Schaller SJ, Anstey M, Blobner M, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016; 388:1377.
  14. Morris PE, Berry MJ, Files DC, et al. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2016; 315:2694.
  15. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63:e61.
  16. Carson SS, Cox CE, Wallenstein S, et al. Effect of Palliative Care-Led Meetings for Families of Patients With Chronic Critical Illness: A Randomized Clinical Trial. JAMA 2016; 316:51.
  17. Kor DJ, Carter RE, Park PK, et al. Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial. JAMA 2016; 315:2406.
  18. Centers for Disease Control and Prevention. Healthcare-assocated infection. Multistate outbreak of Burkholderia cepacia infections. (Accessed on July 14, 2016).
  19. US Food and Drug Administration. Oral liquid docusate sodium by PharmaTech: Recall - contaminated with B. cepacia. (Accessed on July 19, 2016).
  20. Sakles JC, Mosier JM, Patanwala AE, et al. First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department. Acad Emerg Med 2016; 23:703.
  21. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14:1308.
  22. Gaudry S, Hajage D, Schortgen F, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med 2016; 375:122.
  23. Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA 2016; 315:2190.
  24. Patel BK, Wolfe KS, Pohlman AS, et al. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2016; 315:2435.
  25. Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54:115.
  26. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med 2016; 194:265.
  27. Lauritsen J, Kier MG, Bandak M, et al. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin. J Clin Oncol 2016; 34:1492.
  28. Townsley DM, Dumitriu B, Liu D, et al. Danazol Treatment for Telomere Diseases. N Engl J Med 2016; 374:1922.
  29. Nathan SD, Albera C, Bradford WZ, et al. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax 2016; 71:429.
  30. McEvoy RD, Antic NA, Heeley E, et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med 2016; 375:919.
  31. Imbach LL, Büchele F, Valko PO, et al. Sleep-wake disorders persist 18 months after traumatic brain injury but remain underrecognized. Neurology 2016; 86:1945.
  32. Donovan LM, Kapur VK. Prevalence and Characteristics of Central Compared to Obstructive Sleep Apnea: Analyses from the Sleep Heart Health Study Cohort. Sleep 2016; 39:1353.
  33. Qaseem A, Kansagara D, Forciea MA, et al. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2016; 165:125.
  34. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46:327.
  35. Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183:96.
  36. FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. (Accessed on May 26, 2016).
Topic 8355 Version 6816.0

Topic Outline



All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.