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6
culated as described by Livak and Schmittgen.2 The
bars show mean values; T bars indicate standard de-
5 P<0.05 viations. Three independent experiments were per-
4
formed at each time point.
3
2
1 on the maintenance of cortical bone homeostasis
0
Day 0 Day 14 Day 28 than do antibodies to only sclerostin.
Francesca Gori, Ph.D.
B Dkk1 mRNA Expression in Bone Marrow–Derived Harvard School of Dental Medicine
Osteoblasts Boston, MA
10
Andrea Superti-Furga, M.D.
9
Lausanne University
8 Lausanne, Switzerland
P<0.05
7
Roland Baron, D.D.S., Ph.D.
Fold Difference
6
Harvard School of Dental Medicine
5 Boston, MA
4 P<0.05 roland_baron@hms.harvard.edu
3 Since publication of their article, the authors report no fur-
2
ther potential conflict of interest.
A B
Figure 1. High-Grade Airway Injury from Smoke and Sample of Bronchoalveolar-Lavage Fluid Recovered from Patients
with Smoke-Inhalation Injury.
Injury from smoke is shown in Panel A and bronchoalveolar-lavage fluid in Panel B.
also be viewed as a reason to refrain from hastily ratus worn during the knockdown phase. The
dismissing its use in the management of fire- finer particles may undergo diapedesis, thus ex-
related inhalation injury. We hope that further posing the systemic circulation to carcinogenic
studies and discussion will help to clarify this and other hazardous particulates2 as often as six
issue. times per month. Physicians and other health
Hugo G. de Oliveira, Ph.D. care providers who treat firefighters need to re-
Hospital de Clínicas de Porto Alegre mind firefighters and their managers of the in-
Porto Alegre, Brazil sidious risks associated with the failure to use
hugo@hugooliveira.org
a breathing apparatus during fire overhaul. Al-
Vinícius A. Guerra, M.D. though uncomfortable, the self-contained breath-
Marli M. Knorst, Ph.D. ing apparatus must be worn until overhaul has
Universidade Federal do Rio Grande do Sul
been completed.
Porto Alegre, Brazil
No potential conflict of interest relevant to this letter was re- Lawrence W. Raymond, M.D.
ported. Carolinas HealthCare System
Charlotte, NC
1. Sheridan RL. Fire-related inhalation injury. N Engl J Med larry.raymond@carolinashealthcare.org
2016;375:464-9. No potential conflict of interest relevant to this letter was re-
2. Albright JM, Davis CS, Bird MD, et al. The acute pulmonary ported.
inflammatory response to the graded severity of smoke inhala-
tion injury. Crit Care Med 2012;40:1113-21. 1. Baxter CS, Ross CS, Fabian T, et al. Ultrafine particle expo-
3. Hassan Z, Wong JK, Bush J, Bayat A, Dunn KW. Assessing the sure during fire suppression — is it an important contributory
severity of inhalation injuries in adults. Burns 2010;36:212-6. factor for coronary heart disease in firefighters? J Occup Environ
DOI: 10.1056/NEJMc1611256 Med 2010;52:791-6.
2. IARC monographs on the evaluation of carcinogenic risks to
humans. Lyon, France: International Agency for Research on
To the Editor: Sheridan provides an update on Cancer (http://monographs.iarc.fr/).
the pathophysiology and treatment of those who DOI: 10.1056/NEJMc1611256
inhale the hot gaseous and particulate products
of combustion, including thermal degradation To the Editor: We appreciated Sheridan’s dis-
products. Less dramatic but equally important to cussion of the strategies recommended for the
firefighters is the more insidious exposure dur- care of victims of smoke inhalation, but the issue
ing fireground “overhaul,” which follows the of concurrent cyanide toxicity needs more dis-
knockdown phase of firefighting. As described cussion. Although the epidemiology of cyanide
and illustrated by Baxter et al.,1 the air overlying toxicity from smoke inhalation is unknown, cya-
the overhaul site contains high concentrations of nide appears to be a major contributor to lethality
fine and ultrafine particulates, gases, and vapors in some fires.1,2 Unfortunately, laboratory confir-
that can gain ready access to the alveolar–capil- mation of cyanide toxicity cannot be accom-
lary networks of the lungs of firefighters who plished in a clinically meaningful time frame.
have removed the self-contained breathing appa- Hyperlactatemia is a useful surrogate marker of
cyanide toxicity because of its rapid turnaround cyanide exposure, the administration of nitrites
time. Research by Baud et al. showed that in vic- may cause clinical deterioration. If clinicians
tims of residential fires, a plasma lactate level of elect to treat a patient for cyanide toxicity, we
10 mmol per liter or more on hospital admission recommend using hydroxocobalamin, without
strongly correlated with a blood cyanide concen- the administration of nitrites. In addition, car-
tration that was higher than the accepted range boxyhemoglobin levels should be measured be-
in which it is fatal.3 fore antidote administration, since hydroxoco-
Clinicians must maintain a high index of sus- balamin can interfere with co-oximetry.2
picion for cyanide toxicity in patients with inha- Michael Levine, M.D.
lation injuries who present with hemodynamic Meghan Spyres, M.D.
instability, coma, seizures, severe acidemia, or University of Southern California
plasma lactate levels above 10 mmol per liter. Los Angeles, CA
mdlevine@usc.edu
These findings are indications for empirical ad-
No potential conflict of interest relevant to this letter was re-
ministration of hydroxocobalamin. Because hy- ported.
droxocobalamin may interfere with analytical
1. Moore SJ, Norris JC, Walsh DA, Hume AS. Antidotal use of
assays, including measures of carboxyhemoglo- methemoglobin forming cyanide antagonists in concurrent car-
bin, all necessary blood samples should be col- bon monoxide/cyanide intoxication. J Pharmacol Exp Ther 1987;
lected before this agent is administered.4 242:70-3.
2. Pace R, Bon Homme M, Hoffman RS, Lugassy D. Effects of
Morgan A.A. Riggan, M.D. hydroxocobalamin on carboxyhemoglobin measured under physi-
Robert S. Hoffman, M.D. ologic and pathologic conditions. Clin Toxicol (Phila) 2014;52:
New York University School of Medicine 647-50.
New York, NY DOI: 10.1056/NEJMc1611256
morgan.riggan@nyumc.org
Sophie Gosselin, M.D. The author replies: De Oliveira et al. note that
McGill University Health Centre
some data support the use of bronchoscopy in
Montreal, QC, Canada
No potential conflict of interest relevant to this letter was re-
the management of inhalation injury, particularly
ported. when clearing mucus and secretions from the
airway. However, the amount and quality of data
1. Silverman SH, Purdue GF, Hunt JL, Bost RO. Cyanide toxicity
in burned patients. J Trauma 1988;28:171-6.
supporting the routine use of this invasive proce-
2. Ferrari LA, Giannuzzi L. Assessment of carboxyhemoglobin, dure do not seem to allow for its recommenda-
hydrogen cyanide and methemoglobin in fire victims: a novel tion as a standard of care in all patients.
approach. Forensic Sci Int 2015;256:46-52.
3. Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide
Raymond reminds us of the dangers associat-
concentrations in victims of smoke inhalation. N Engl J Med ed with the inhalation of toxic substances, even
1991;325:1761-6. after fires have been extinguished. This is very
4. Livshits Z, Lugassy DM, Shawn LK, Hoffman RS. Falsely low
carboxyhemoglobin level after hydroxocobalamin therapy. N Engl
prudent advice, particularly for firefighters, as
J Med 2012;367:1270-1. Raymond notes.
DOI: 10.1056/NEJMc1611256 Riggan et al. comment that hydrogen cyanide
may contribute to the risk of death from burns.
To the Editor: Sheridan correctly acknowledges Although hydrogen cyanide may be a likely con-
the controversy surrounding the need to treat pa- tributor in some situations, as yet the data have
tients with smoke-inhalation injury for cyanide not supported the routine treatment of all pa-
toxicity. Table 1 of his article lists sodium nitrite tients with inhalation injury for cyanide intoxi-
and sodium thiosulfate, in addition to hydroxoco- cation. Levine and Spyres appropriately note that
balamin, as potential therapies for suspected cya- hydroxocobalamin may be a less toxic means of
nide toxicity. We believe that this approach is prob- treating cyanide poisoning than nitrites in pa-
lematic. Nitrites induce methemoglobinemia and tients for whom such treatment is believed to be
subsequently decrease oxygen-carrying capacity. necessary.
In patients with carbon monoxide poisoning, oxy- Robert L. Sheridan, M.D.
gen-carrying capacity is already impaired, and the Harvard Medical School
coadministration of nitrites may be detrimental.1 Boston, MA
rsheridan@mgh.harvard.edu
Thus, while we agree that it may be unclear
Since publication of his article, the author reports no further
whether a patient with smoke inhalation injury potential conflict of interest.
whose condition is stable should be treated for DOI: 10.1056/NEJMc1611256