What's new in pulmonary and critical care medicine

Official reprint from UpToDate® www.uptodate.com

©2018 UpToDate®
What's new in pulmonary and critical care medicine
Authors: Helen Hollingsworth, MD, April F Eichler, MD, MPH, Geraldine Finlay, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Nov 2018. | This topic last updated: Dec
14, 2018.

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.

ASTHMA

Low-allergenicity landscaping plants (November 2018)

Patients with allergic rhinoconjunctivitis or asthma and landscapers sometimes

ask about modifying outdoor environments to favor plants that are less likely to
cause symptoms. The first listing of plants of low allergenic potential, as well as
general guidance on producing a low-allergenic landscape, has been created
by the Landscape Allergen Working Group of the American Academy of Allergy,
Asthma and Immunology [1]. In general, trees, shrubs, and flowering plants
with heavier versus lighter pollen are less allergenic, because heavier pollen is
transported by insects rather than traveling through the air. (See "Allergen
avoidance in the treatment of asthma and allergic rhinitis", section on 'Outdoor
allergens'.)

Omalizumab and rhinovirus-associated asthma exacerbations (August

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2018)

The anti-IgE monoclonal antibody omalizumab reduces the rate of asthma

exacerbations, including those associated with rhinoviral infections. The
mechanism by which this occurs has been a focus of several recent studies
and appears to be related to the impaired ability of plasmacytoid dendritic cells
(pDCs) in patients with atopy to produce interferon-alpha (IFN-alpha) in
response to viral infection [2]. In patients with allergic asthma, cross-linking of
IgE on the surface of these cells suppresses IFN-alpha production, and serum
IgE levels correlate with the level of impairment. Omalizumab therapy
ameliorates this by binding free IgE and downregulating IgE receptors on the
surface of pDCs, thus normalizing interferon production. (See "Anti-IgE
therapy", section on 'Reduction of exacerbations related to viral infections'.)

Long-term risk of respiratory and allergic illnesses following

tonsillectomy and adenoidectomy in childhood (July 2018)

It is unclear if children undergoing tonsillectomy and/or adenoidectomy are at

increased risk of developing respiratory or allergic illnesses later in life. In the
largest study addressing this question to date, which involved >1 million
children followed for 10 to 30 years, rates of respiratory and allergic illnesses
(eg, asthma, eczema, upper respiratory illness, pneumonia) were higher among
children who underwent tonsillectomy and/or adenoidectomy than those who
did not undergo surgery [3]. Whether the surgery itself increased the risk for
these conditions remains uncertain. The observed association may be
explained by underlying factor(s) that predispose both to conditions commonly
treated with tonsillectomy and adenoidectomy (eg, obstructive sleep apnea,
recurrent otitis media) and other respiratory and allergic illnesses. (See
"Tonsillectomy (with or without adenoidectomy) in children: Postoperative care
and complications", section on 'Potential long-term effects'.)

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Intermittent versus daily controller medication for mild asthma (June

2018)

Two 52-week randomized trials with over 8000 total participants (≥12 years)
have addressed the question whether adults and adolescents with mild
persistent asthma can be managed with an "as needed" controller strategy to
reduce the total exposure to inhaled glucocorticoids. In both trials, formoterol,
which has both a rapid onset and a long duration of action, was paired with
budesonide for as-needed therapy.

● The larger trial compared three strategies: twice-daily placebo plus inhaled
terbutaline as needed, twice-daily placebo plus budesonide-formoterol as
needed, or budesonide twice daily plus terbutaline as needed [4]. The
annual rate of severe exacerbations was similar in both budesonide arms
and lower than with terbutaline alone. Symptom control in those taking as-
needed budesonide-formoterol was inferior to budesonide maintenance,
but superior to terbutaline as needed.

● Another trial compared budesonide-formoterol taken as needed with

budesonide taken twice daily [5]. Budesonide-formoterol was noninferior to
budesonide maintenance for the rate of severe exacerbations. The time to
first exacerbation was similar between the groups. As with the previous
trial, symptom control in those taking as-needed budesonide-formoterol
was inferior to budesonide maintenance.

Prescribing controller medications on an as-needed basis is considered

experimental and has not been incorporated into asthma treatment guidelines.
(See "Treatment of intermittent and mild persistent asthma in adolescents and
adults", section on 'Combination budesonide plus formoterol or SABA as
needed'.)

Dupilumab for severe asthma (June 2018)

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Dupilumab is a monoclonal antibody directed against the alpha subunit of the

interleukin 4 (IL-4) receptor that is approved in the United States for use in
atopic dermatitis and, more recently, moderate-to-severe eosinophilic asthma.
In a multicenter trial, over 1900 patients ≥12 years of age with poorly controlled
asthma were randomly assigned to one of two doses of dupilumab or placebo,
injected subcutaneously, every two weeks for 52 weeks [6]. The annualized
rates of severe exacerbations were decreased by approximately one-half in the
dupilumab groups compared with placebo, and lung function was improved.
The treatment effect appeared greater among participants with a baseline blood
eosinophil count ≥300/microL or with an elevated fraction of exhaled nitric oxide
(FENO). Transient peripheral blood eosinophilia was noted in 4 percent of those
taking dupilumab. (See "Treatment of severe asthma in adolescents and
adults", section on 'Anti-lL-4 receptor alpha subunit antibody'.)

COPD

Prophylactic antibiotics in patients with COPD (November 2018)

Prophylactic antibiotics are a proposed strategy to improve outcomes in

patients with chronic obstructive pulmonary disease (COPD), although the risk-
benefit trade-off is unclear. In a systematic review of 14 randomized trials
evaluating almost 4000 patients, prophylactic antibiotic use of any kind reduced
the proportion of patients with acute exacerbations (47 versus 61 percent with
placebo) [7]. Prophylaxis also resulted in small trends toward improvement in
the number of hospital admissions, serious adverse events, and all-cause
mortality, but none were statistically significant. Furthermore, the potential risks
associated with antibiotic use (eg, development of antibiotic resistance) were
not adequately evaluated. We reserve prophylactic antibiotics for selected
patients with frequent COPD exacerbations, weighing the risks and benefits in
each individual. (See "Management of infection in exacerbations of chronic
obstructive pulmonary disease", section on 'Prophylactic antibiotics'.)
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Procalcitonin levels in the management of COPD exacerbations (October

2018)

Procalcitonin levels can help distinguish bacterial infection from other causes of
infection or inflammation, but the role of this test in guiding treatment for acute
exacerbation of chronic obstructive pulmonary disease (AECOPD) is
controversial. In a trial of 302 patients admitted to the intensive care unit with
severe AECOPD and suspected lower respiratory tract infection, short-term
mortality rates were higher with procalcitonin-guided care versus guideline-
concordant care (20 versus 14 percent) [8]. The mortality difference was
highest among patients who did not receive antibiotics at initial presentation (31
versus 12 percent). This study highlights the importance of early antibiotic
administration in severely ill patients with suspected infection, regardless of
procalcitonin levels, and suggests that the promise of procalcitonin likely lies in
guiding antibiotic discontinuation rather than initiation in patients with AECOPD.
(See "Procalcitonin use in lower respiratory tract infections", section on 'Acute
exacerbations of chronic obstructive pulmonary disease'.)

Endobronchial valve placement for severe emphysema (August 2018)

Endobronchial valves (EBVs) are placed bronchoscopically in a lung region

with severe emphysema, so air can exit but not re-enter the bronchus. This
promotes atelectasis of the distal emphysematous lung and thereby improves
ventilation of less diseased areas. Previously published randomized trials in
patients with severe emphysema have reported modest improvements in
symptoms and lung function after placement of EBVs [9,10]. Based on these
trials, the US Food and Drug Administration (FDA) has approved use of the
Zephyr EBV [11]. Thus, for patients with hyperinflation due to severe
emphysema who remain symptomatic despite optimal medical therapy and
pulmonary rehabilitation, we suggest placement of EBVs in the lung region with
the most emphysematous destruction and little to no collateral ventilation.
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Placement of EBVs requires specialized training and equipment and carries a

high risk of pneumothorax, and thus continuing current therapy is a reasonable
alternative. (See "Management of refractory chronic obstructive pulmonary
disease", section on 'Endobronchial valves'.)

CRITICAL CARE

Extubation to noninvasive ventilation (November 2018)

The ideal way to achieve successful and early liberation from mechanical
ventilation is unclear. A recent randomized, open-label trial of critically ill
patients who were ready to be weaned compared early extubation to
noninvasive ventilation (NIV) with the current standard (extubation only after a
successful spontaneous breathing trial [SBT]) [12]. Patients in the extubate to
NIV group received fewer days of mechanical ventilation and had a shorter
intensive care unit (ICU) length of stay, but there was no impact on mortality or
on rates of reintubation and tracheostomy. The rigorous selection process for
trial entry and aggressive care given to patients receiving NIV may not be
generalizable to usual care environments. Further trials are needed before
early extubation to NIV can be routinely applied to patients who are ready to be
weaned from mechanical ventilation. (See "Methods of weaning from
mechanical ventilation", section on 'Weaning failure'.)

Guidelines on oxygenation goals for hospitalized patients (November

2018)

It is well known that hyperoxia is harmful, but oxygenation goals in hospitalized

patients with acute illness are unclear. A recent meta-analysis of 25 trials that
included a heterogenous group of hospitalized patients requiring supplemental
oxygen reported increased mortality in patients supplemented to a peripheral
oxygen saturation (SpO2) ≥96 percent [13]. Guidelines were generated based
on these data, identifying oxygen strategies targeting specific patient
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populations, including those with myocardial infarction and stroke. We believe

the generalizability of these data is limited due to the heterogeneous nature of
the patient populations studied. Nonetheless, we support a general strategy
that individualizes oxygenation goals and generally avoids raising the SpO2 >96
percent, unless higher goals are specifically indicated. (See "Overview of
mechanical ventilation", section on 'Fraction of inspired oxygen'.)

No benefit of oral and digestive tract decontamination when antibiotic

resistance is prevalent (November 2018)

Modest mortality benefits have been demonstrated among intensive care unit
(ICU) patients treated with orally applied or ingested non-absorbable
antimicrobials (selective oropharyngeal and digestive decontamination [SOD
and SDD]) in trials from the Netherlands, a region with low baseline
antimicrobial resistance. However, in a trial among European ICUs with a
moderate to high prevalence of antibiotic resistance, chlorhexidine mouthwash,
SOD, and SDD were not associated with reductions in mortality or in ICU-
acquired multidrug-resistant gram-negative bacteremia compared with baseline
care [14]. These findings support the current practice of ICUs with a moderate
to high prevalence of antibiotic resistance to forgo SOD and SDD. (See
"Infections and antimicrobial resistance in the intensive care unit: Epidemiology
and prevention", section on 'Digestive and oropharyngeal decontamination'.)

Timing of renal replacement therapy in patients with acute kidney injury

and septic shock (November 2018)

The optimal timing of initiating renal replacement therapy (RRT) for patients
with sepsis and severe acute kidney injury (AKI) is unclear. A randomized trial
of nearly 500 patients compared earlier (within 12 hours of AKI diagnosis)
versus delayed (development of an emergent indication for RRT or at 48 hours
after AKI diagnosis) initiation of RRT in patients with early septic shock and

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severe AKI [15]. There was no difference in mortality at 90 days between the
groups, although the trial was stopped early for futility. These findings support
our recommendation not to electively initiate RRT in patients with severe AKI
without an urgent indication, such as clinically significant uremic symptoms,
severe electrolyte abnormalities, or volume overload. (See "Renal replacement
therapy (dialysis) in acute kidney injury in adults: Indications, timing, and
dialysis dose", section on 'Timing of elective initiation'.)

Cricoid pressure for rapid sequence induction and intubation (October

2018)

The literature on the benefits and risks of cricoid pressure during rapid
sequence induction and intubation (RSII) is inconclusive. The first large
multicenter randomized trial, which included nearly 3500 patients who required
RSII for general anesthesia, reported no difference in the incidence of
aspiration with and without cricoid pressure (0.6 versus 0.5 percent) [16].
Median intubation time was longer in patients who had cricoid pressure applied
(27 versus 23 seconds), and there was higher incidence of Cormack Lehane
grade 3 or 4 laryngeal views with cricoid pressure (10 versus 5 percent).
Practice varies, and some UpToDate contributors routinely use cricoid pressure
for RSII, while others do not. If used, cricoid pressure may have to be released
if intubation proves difficult. (See "Rapid sequence induction and intubation
(RSII) for anesthesia", section on 'Cricoid pressure controversies'.)

Bedside ultrasonography in patients with undifferentiated hypotension

(September 2018)

Observational evidence supports point-of-care (POC) ultrasonography for the

bedside assessment of patients with undifferentiated hypotension. However, a
recent randomized trial in over 250 patients seen in an emergency department
with undifferentiated hypotension found that POC ultrasonography did not alter

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the 30-day survival, CT scanning rate, inotrope or intravenous fluid use, or

length of stay [17]. A large number of exclusion criteria and a relatively small
study population may have limited the ability of the trial to detect an impact of
bedside ultrasonography. We reserve POC ultrasonography for patients with
undifferentiated hypotension in whom a diagnosis has not been suggested by
standard clinical and laboratory testing, or for those in whom definitive imaging
is unsafe. (See "Evaluation of and initial approach to the adult patient with
undifferentiated hypotension and shock", section on 'Point-of-care
ultrasonography'.)

Society guidelines on sedation for agitated adults in the ICU (September

2018)

The Society of Critical Care Medicine (SCCM) recently issued guidelines on

sedation of agitated patients in the intensive care unit (ICU) [18]. Compared
with 2013 guidelines, the new recommendations focus on minimizing sedation,
regular use of protocols and daily awakening strategies, screening for delirium,
and early mobilization in the ICU. They continue to endorse the avoidance of
benzodiazepines when feasible, treatment of pain when present, and promote
use of propofol or dexmedetomidine for select subgroups. UpToDate authors
agree with the SCCM strategies. (See "Sedative-analgesic medications in
critically ill adults: Selection, initiation, maintenance, and withdrawal" and "Post-
intensive care syndrome (PICS)".)

Glucocorticoid therapy for sepsis (September 2018)

Two new meta-analyses summarize the effect of glucocorticoids in patients with

sepsis and septic shock [19,20]. Both analyses, in agreement with previous
studies, found that glucocorticoid administration (typically hydrocortisone)
resulted in faster resolution of shock with no or minimal effect on mortality.
Glucocorticoids also appear to reduce the duration of mechanical ventilation

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and length of intensive care unit or hospital stay but increase the risk of
adverse effects including hypernatremia, hyperglycemia, and neuromuscular
weakness. These results support our recommendation to evaluate the use of
glucocorticoid therapy on a case-by-case basis and, in general, to reserve
administration of glucocorticoid therapy for those with refractory septic shock.
(See "Glucocorticoid therapy in septic shock", section on 'Meta-analyses'.)

Infectious Diseases Society of America position paper regarding 2016

sepsis guidelines (September 2018)

A position paper issued by the Infectious Diseases Society of America (IDSA)

does not endorse the Society of Critical Care Medicine/European Society of
Intensive Care Medicine (SCCM/ESICM) 2016 Surviving Sepsis Campaign
guidelines for the management of sepsis and septic shock [21]. In particular,
while the IDSA agrees that the SCCM/ESICM recommendations are life-saving
for patients with septic shock, they may lead to overtreatment for those with
milder variants of sepsis and sepsis syndromes. The IDSA does not endorse
routine initiation of antibiotic therapy within one hour of suspecting sepsis, nor
administration of combination antibiotic therapy and a 7 to 10 day course of
antibiotic therapy for all patients, regardless of presentation factors. The IDSA
also notes unclear recommendations for removal of catheters when considered
as the source of sepsis, and for the role of calcitonin when following the
therapeutic response. UpToDate agrees with the IDSA on many of these
issues, as outlined in our topic on management of sepsis and septic shock.
(See "Evaluation and management of suspected sepsis and septic shock in
adults", section on 'Introduction'.)

Guidelines for prevention and management of pain in critically ill patients

(September 2018)

Opioids remain a mainstay for pain management in many critically ill patients,

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as noted in the 2018 Pain, Agitation/sedation, Delirium, Immobility

(rehabilitation/mobilization), and Sleep (PADIS) guidelines of the Society of
Critical Care Medicine [18]. Compared with the 2013 guidelines, the current
guidelines suggest using the lowest effective doses of opioids and a multimodal
approach for pain management. This approach may include opioid analgesics,
nonopioid agents such as intravenous acetaminophen, ketamine, neuropathic
pain medications (eg, gabapentin, pregabalin, carbamazepine), nonsteroidal
antiinflammatory drugs (NSAIDs), or nefopam, as well as regional anesthesia,
and other adjunct therapies (eg, massage, music, relaxation techniques). (See
"Pain control in the critically ill adult patient", section on 'Multimodal analgesia'.)

Use of ECMO for postcardiotomy cardiogenic shock (July 2018)

In a meta-analysis of 31 studies (nearly 3000 patients) receiving venoarterial

extracorporeal membrane oxygenation (ECMO) for postcardiotomy cardiogenic
shock unresponsive to high-dose inotropic support, approximately one-third
survived to hospital discharge [22]. A subsequently published single-center
study reported similar results [23]. Factors associated with survival in both
studies included younger age, lower baseline blood lactate levels, and use of
ECMO as a bridge to cardiac transplantation. Prediction of outcome after
ECMO insertion in this setting is challenging due to heterogeneity of specific
patient- and procedure-related reasons for failure to wean from
cardiopulmonary bypass. (See "Management of intraoperative problems after
cardiopulmonary bypass", section on 'Extracorporeal membrane oxygenation'.)

Incidence of and risk factors for overly rapid correction of hyponatremia

(July 2018)

In patients with severe hyponatremia (serum sodium <120 mEq/L), overly rapid
correction of the serum sodium (defined as an increase of more than 8 mEq/L
in a 24-hour period) may produce serious neurologic manifestations referred to

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as the osmotic demyelination syndrome. In a large retrospective cohort study of

hospitalized patients admitted with serum sodium <120 mEq/L, overly rapid
correction at 24 hours was identified in 41 percent [24]. A lower initial serum
sodium was an independent risk factor for overly rapid correction, as were
schizophrenia and a lower baseline urine sodium concentration (factors which
often correspond to an etiology of hyponatremia that is quickly reversible). Of
the patients with overly rapid correction, 1 percent developed osmotic
demyelination syndrome, of whom most had hypovolemia, hypokalemia, and a
history of alcohol use and/or malnutrition. Overly rapid correction is common
among patients with severe hyponatremia and may produce devastating
neurologic consequences. (See "Osmotic demyelination syndrome (ODS) and
overly rapid correction of hyponatremia", section on 'Causes of overly rapid
correction'.)

Risks of hydroxyethyl starch 130/0.4 colloid solution in elective surgical

patients (July 2018)

Concern has been raised about risks associated with the use of hydroxyethyl
starch (HES) solutions in critically ill patients due to association with increased
risk of acute kidney injury (AKI) and possibly increased mortality. In a 2018
observational study of over 2000 patients undergoing elective major or minor
surgery, there was no association between administration of a low substituted
HES 130/0.4 solution, compared with a balanced crystalloid solution, and
postoperative AKI requiring renal replacement therapy (RRT) [25]. Previous
meta-analyses of randomized trials in surgical patients have also noted no
differences in the incidence of AKI or RRT after administration of low
substituted HES solutions compared with other types of fluid therapy, although
data are inconsistent and some large randomized trials and systematic reviews
in critically ill or mixed surgical and nonsurgical patient populations have
reported a higher incidence of AKI requiring RRT after administration of HES
solutions. We typically select a balanced electrolyte crystalloid solution for
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routine perioperative fluid administration, and we generally avoid administration

of HES solutions. (See "Intraoperative fluid management", section on
'Hydroxyethyl starches'.)

Outcomes after restrictive versus liberal transfusion strategies in cardiac

surgical patients (July 2018)

The optimal Hgb level during and after cardiac surgery is not known. In a
multicenter randomized trial conducted in more than 5000 cardiac surgical
patients, the primary composite outcome that included death, myocardial
infarction, renal failure, and stroke was similar with use of a restrictive
transfusion strategy (Hgb trigger set at <7.5 g/dL) compared with use of a
liberal transfusion strategy (Hgb trigger set at <9.5 g/dL) during the
intraoperative and postoperative periods [26]. In the restrictive group, patients
received fewer blood transfusions. At follow-up six months later, the primary
composite outcome did not differ between the two groups, nor did mortality [27].
Most other randomized trials in cardiac surgical patients have noted similar
results, with fewer RBC transfusions and similar postoperative outcomes for
restrictive versus liberal transfusion strategies. We employ a restrictive
transfusion approach, with a Hgb trigger of 7 to 8 g/dL, for most cardiac surgical
patients. (See "Management of intraoperative problems after cardiopulmonary
bypass", section on 'Anemia'.)

Bicarbonate therapy for critically ill patients with metabolic acidosis

(June 2018)

While indications for bicarbonate therapy in metabolic acidosis are

controversial, most experts treat patients who have acute metabolic acidosis
and severe acidemia (ie, arterial pH <7.1) with bicarbonate therapy. There is
less consensus about treatment of patients with less severe acidemia (eg, pH
7.1 to 7.2). A randomized trial assigned 389 critically ill patients with metabolic

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acidosis (mean serum bicarbonate, 13 mmol/L, and most with elevated lactate
levels) and acidemia (arterial pH ≤7.2, mean 7.15) to either intravenous
infusions of sodium bicarbonate to maintain a pH >7.3 or to no sodium
bicarbonate [28]. Bicarbonate therapy had no overall effect on mortality at 28
days or organ failure at seven days, although there was a trend toward
improved outcomes in the bicarbonate group. However, among the subgroup of
patients with severe acute kidney injury (defined as a twofold or greater
increase in serum creatinine or oliguria), bicarbonate therapy reduced 28-day
mortality (46 versus 63 percent) and the need for dialysis (51 versus 73
percent). For patients with acute metabolic acidosis and an arterial pH 7.1 to
7.2, UpToDate suggests bicarbonate therapy when severe acute kidney injury
is also present. (See "Bicarbonate therapy in lactic acidosis", section on 'Which
patients should receive bicarbonate therapy'.)

INTERSTITIAL LUNG DISEASE

Addition of sildenafil of no benefit in advanced idiopathic pulmonary

fibrosis (November 2018)

A substantial portion of patients with advanced idiopathic pulmonary fibrosis

(IPF) develop secondary pulmonary hypertension (PH). This has led to the
hypothesis that, as in pulmonary arterial hypertension, a phosphodiesterase
inhibitor might improve exercise tolerance or quality of life for such patients. In
a multicenter trial, almost 300 patients with advanced IPF were assigned to
nintedanib plus either sildenafil or placebo for 24 weeks [29]. Sildenafil
provided no significant benefit in quality of life or dyspnea. In concert with
current guidelines, sildenafil is not advised for routine use in IPF. (See
"Treatment of idiopathic pulmonary fibrosis", section on 'Phosphodiesterase
inhibitors'.)

LUNG CANCER

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Smoking and lung cancer mortality (October 2018)

In the United States, lung cancer occurs in approximately 250,000 people

annually and is frequently smoking-related. However, efforts have been made
to curb tobacco use over the past 50 years. A modeling study based on
smoking and lung cancer mortality data in the United States since the 1960s
projected a decrease in age-adjusted smoking-related lung cancer mortality by
79 percent between 2015 and 2065 [30]. We continue to encourage tobacco
cessation to decrease the risk of lung cancer, among other health benefits.
(See "Cigarette smoking and other possible risk factors for lung cancer",
section on 'Epidemiology'.)

Bioengineered tracheobronchial reconstruction using stented aortic

matrices (June 2018)

Large proximal tumors of the trachea or proximal bronchus are generally

considered inoperable, and treatment is mostly palliative. A recent study
described the outcomes of 13 patients with tracheobronchial lesions who
underwent radical resection followed by airway reconstruction with a novel
technique that used cryopreserved aortic allografts and stenting to generate a
new airway [31]. At 90 days, there were no deaths and no adverse events
related to the surgery. Stents were removed at about 18 months and at four
years, 79 percent of patients remained alive, the majority of whom were able to
breathe through their newly formed airway. This technique remains
investigational but offers future promise to those with inoperable
tracheobronchial lesions. (See "Clinical presentation, diagnostic evaluation, and
management of central airway obstruction in adults", section on
'Investigational'.)

PLEURAL DISEASE

Guidelines for management of malignant pleural effusions (October 2018)

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The American Thoracic Society (ATS), Society of Thoracic Surgeons (STS),

and Society of Thoracic Radiology (STR) issued guidelines regarding the
management of malignant pleural effusions (MPEs) [32]. Emphasis is placed on
the use of ultrasound for guidance of pleural interventions, treatment only for
symptomatic effusions, and use of manometry during large-volume
thoracentesis. Other recommendations include indwelling catheter (IPC)
placement or chemical pleurodesis for long-term management of those with
expandable lung, while pleurodesis is not suggested as an option for patients
with unexpandable lung. UpToDate topics are in general agreement with these
guidelines. (See "Management of malignant pleural effusions", section on
'Indications for treatment'.)

PULMONARY VASCULAR DISEASE

Endothelin receptor antagonist for Eisenmenger syndrome (December

2018)

Advanced therapy including endothelin receptor antagonists (eg, bosentan or

macitentan) is widely accepted for select patients with pulmonary arterial
hypertension (PAH), but consensus is lacking for those with PAH and
congenital heart disease, including Eisenmenger syndrome. In the MAESTRO
trial, including over 200 patients with Eisenmenger syndrome with World Health
Organization (WHO) functional class II to IV, macitentan versus placebo
resulted in a similar mean change in six-minute walk distance (6MWD), but
reduced pulmonary vascular resistance [33]. In the smaller prior BREATHE-5
trial, bosentan improved both of these measures relative to placebo. We
continue to use endothelin receptor antagonists for patients with PAH and
congenital heart disease given improvement in hemodynamic parameters,
although an effect on clinical outcomes has not been established. (See
"Management and prognosis of pulmonary hypertension in adults with
congenital heart disease", section on 'Endothelin receptor antagonist'.)
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CTPA protocol for suspected pulmonary embolism in pregnancy

(November 2018)

Protocols involving pretest probability assessment (PTP), D-dimer testing, and

computed tomographic pulmonary angiography (CTPA) are typically used in
nonpregnant patients with a suspected pulmonary embolism (PE) but avoided
during pregnancy. The value of such a protocol, which also included
compression ultrasonography, was studied in a prospective trial of 395
pregnant women with suspected PE [34]. PE was excluded in patients with a
low or intermediate clinical PTP and a negative D-dimer or in those with a
negative CTPA. Among those in whom PE was excluded, no patient developed
symptomatic venous thromboembolism. However, the significant proportion of
protocol deviations and low proportion of women having a negative D-dimer
with increasing gestational age may limit the value of this protocol. (See
"Pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and
diagnosis", section on 'Investigational algorithm (CTPA)'.)

Rivaroxaban prophylaxis for venous thromboembolism following

discharge not indicated (September 2018)

A recent trial studied the efficacy of the direct oral anticoagulant, rivaroxaban, in
medical patients at risk of venous thromboembolism (VTE) following hospital
discharge [35]. Compared with placebo, 45 days of rivaroxaban had a marginal
effect on reducing the rates of nonfatal symptomatic VTE but had no effect on
VTE-related death. Although rates of major bleeding were higher with
rivaroxaban, the overall incidence was low in both groups (<0.3 percent). This
study is consistent with previous data in medical patients that do not support a
recommendation for VTE prophylaxis in the extended setting. (See "Prevention
of venous thromboembolic disease in acutely ill hospitalized medical adults",
section on 'Duration of prophylaxis'.)

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SLEEP MEDICINE

Poor sleep quality and quantity in hospitalized patients (September 2018)

Two recent studies highlight sleep disturbances in hospitalized patients as a

common and potentially modifiable problem that could improve outcomes. In a
cross-sectional survey study involving 39 hospitals in the Netherlands and
nearly 1500 patients, subjectively reported total sleep time was approximately
80 minutes shorter among inpatients compared with their habitual sleep times
at home over the prior month, and 70 percent of patients reported being
awakened by external causes [36]. In a separate study, a multimodal
intervention targeting sleep (eg, reduced nighttime noise, delayed morning
phlebotomy) plus access to daily health information via a patient portal led to an
improvement in factors impacting sleep duration and quality, as well as length
of stay and readmission rates, over a 2.5-year period [37]. (See "Poor sleep in
the hospital: Contributing factors and interventions", section on 'Reduced total
sleep time'.)

Arousal-based criteria for hypopneas reaffirmed (September 2018)

Based upon an increasing body of data demonstrating that respiratory event-

related arousals from sleep are associated with morbidity, even in the absence
of related oxygen desaturations, the American Academy of Sleep Medicine
(AASM) has issued a statement confirming the recommended definition of
hypopnea, which includes diminished airflow accompanied by either ≥3 percent
oxygen desaturation or an arousal from sleep [38]. Use of an alternative
definition of hypopnea, which does not include arousal as a criterion (and which
is sometimes mandated by insurers), should be performed alongside, not in
place of, the recommended criteria. (See "Polysomnography in the evaluation
of sleep-disordered breathing in adults", section on 'Hypopneas'.)

OTHER PULMONARY MEDICINE

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Oral versus parenteral agents for multidrug-resistant tuberculosis (MDR-

TB) (October 2018)

Treatment of multidrug-resistant tuberculosis (MDR-TB) usually includes a

parenteral agent for the initial phase of therapy. In a meta-analysis including
more than 12,000 adults with MDR-TB, a significant association was observed
between reduced mortality and use of linezolid, levofloxacin, moxifloxacin, or
bedaquiline, as well as use of regimens containing no injectable drug [39]. In
August 2018, the World Health Organization (WHO) issued an advisory
statement regarding anticipated modifications to their recommended treatment
approach for adults with MDR-TB; the statement prioritizes use of oral agents
over injectable agents [40]. Pending finalization of the WHO guidelines, we
favor substitution of bedaquiline for the injectable agent; expert consultation is
essential. (See "Treatment of drug-resistant pulmonary tuberculosis in adults",
section on 'Conventional regimen'.)

Mortality due to community-acquired pneumonia in the United States

(October 2018)

Community-acquired pneumonia (CAP) is a leading cause of morbidity and

mortality worldwide. In a retrospective review of 2320 adults hospitalized with
CAP at five tertiary care centers in the United States, 52 (2.2 percent) died
during hospitalization [41]. Approximately half of those deaths were directly
attributable to CAP, and more than 60 percent occurred in patients ≥65 years
old and those with multiple comorbidities. A lapse in the quality of care (eg,
delayed or inappropriate antibiotic use) that could have contributed to death
was identified in four patients. While mortality in this study was low, it highlights
that early recognition of those at risk for poor outcomes and prompt treatment is
critical to care. (See "Prognosis of community-acquired pneumonia in adults",
section on 'In-hospital and postdischarge mortality'.)

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Phrenic neuropathy in patients with neuralgic amyotrophy (August 2018)

Unilateral or bilateral phrenic neuropathy causing diaphragm dysfunction can

occur in patients with neuralgic amyotrophy, a common cause of nontraumatic
brachial plexopathy, but it is not well studied and may be overlooked clinically. A
recent study identified over 100 patients with clinical diaphragm dysfunction,
representing approximately 7 percent of a larger cohort of patients with
neuralgic amyotrophy [42]. The most common symptoms were exertional
dyspnea, sleep disturbance, and orthopnea. Supine and sitting spirometry
should be performed in patients suspected of having phrenic neuropathy, as
chest radiograph has suboptimal sensitivity, particularly when involvement is
bilateral. Many patients improve spontaneously within two years, although
others have persistent symptoms. (See "Brachial plexus syndromes", section
on 'Clinical variability'.)

Advisory Committee on Immunization Practices recommendations for

influenza vaccination for the 2018 to 2019 season (August 2018)

The United States Advisory Committee on Immunization Practices

recommendations for the 2018 to 2019 influenza season include live attenuated
influenza vaccine (LAIV) as an option for appropriate patients [43,44]. This is a
change from the previous two influenza seasons, during which LAIV was not
recommended because it had low effectiveness against H1N1 influenza in
children [44]. The manufacturer subsequently changed the H1N1 strain used to
produce the vaccine to one with better replicative fitness and immunogenicity,
comparable to the one used to make the vaccine in prior seasons in which LAIV
was effective against H1N1 viruses. (See "Seasonal influenza vaccination in
adults", section on 'Live attenuated vaccine' and "Seasonal influenza in
children: Prevention with vaccines", section on 'Choice of vaccine'.)

Rifampin for latent tuberculosis infection (August 2018)

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Regimen preference for treatment of latent tuberculosis infection (LTBI) is

based largely on the likelihood of adherence and the potential for adverse
effects; thus far, no regimen has been shown to be of superior efficacy. In two
randomized trials including more than 6800 adults and 800 children with LTBI,
rifampin daily for four months (4R) resulted in similar efficacy for prevention of
active tuberculosis but better adherence rates compared with isoniazid daily for
nine months (9H) [45,46]. Among adults, the rate of adverse events was lower
with 4R than 9H; among children, the rates of adverse events were comparable
with the two regimens. The trial findings support our preference for 4R in adults;
given the findings in children, we now suggest 4R as one of our preferred
options for treatment of children with LTBI. (See "Treatment of latent
tuberculosis infection in HIV-uninfected nonpregnant adults", section on
'Rifampin' and "Latent tuberculosis infection in children", section on 'Rifampin'.)

FDA advises against prophylactic azithromycin after hematopoietic cell

transplantation (August 2018)

A previously published randomized trial in almost 500 patients found that long-
term azithromycin to prevent bronchiolitis obliterans syndrome (BOS) following
hematopoietic cell transplantation (HCT) increased the rate of hematologic
relapse compared with placebo [47]. The cause of the increased relapse rate is
not known. Additionally, azithromycin did not protect against development of
airflow limitation. Based on these data, the US Food and Drug Administration
(FDA) issued a safety alert recommending that long-term azithromycin not be
administered for prophylaxis after HCT for cancers of the blood or lymph nodes
[48]. (See "Pulmonary complications after allogeneic hematopoietic cell
transplantation", section on 'Airflow obstruction and bronchiolitis obliterans'.)

American Thoracic Society guidelines for the diagnosis of primary ciliary

dysfunction (July 2018)

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What's new in pulmonary and critical care medicine

The 2018 American Thoracic Society has published new guidelines for the
diagnosis of primary ciliary dysfunction (PCD) [49]. The guidelines suggest use
of extended panel genetic testing (assessing >12 genes for pathogenic
variants) for PCD diagnosis, where available, as a less labor intensive
alternative to transmission electron microscopy (TEM) (algorithm 1). The
previous standard panel genetic tests (≤12 genes) have a high false negative
rate. However, even the extended panel can miss some cases of PCD. (See
"Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Genetic
testing'.)

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