0
Editorials |

Can We Predict Who Will Develop Chronic Sequelae of Acute Inhalational Injury?Chronic Sequelae of Acute Inhalational Injury FREE TO VIEW

John R. Balmes, MD, FCCP
Author and Funding Information

From the Division of Occupational and Environmental Medicine, University of California, San Francisco and School of Public Health, University of California, Berkeley.

Correspondence to: John R. Balmes, MD, FCCP, University of California, San Franscisco, Division of Occupational and Environmental Medicine, Box 0843, San Francisco, CA 94143; e-mail: john.balmes@ucsf.edu


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(2):278-279. doi:10.1378/chest.12-0126
Text Size: A A A
Published online

The determinants of risk of chronic sequelae of high-dose exposures to inhaled irritants are not well understood.1,2 One of the obstacles to the study of this issue is the lack of predictability about when such events (eg, accidental releases of irritant gases, vapors, dusts, and fumes) will occur. Although an unimaginably horrible incident, the World Trade Center (WTC) disaster has provided the opportunity to learn much about the risk of chronic respiratory disease after massive exposures to fire smoke and a highly alkaline dust.3 Because New York City firefighters had undergone routine medical surveillance with spirometry prior to September 11, 2001, it has been possible to document with continued serial spirometry in the subsequent years that firefighter responders sustained a substantial loss of ventilatory function as a consequence of these exposures.4,5 In addition, Fire Department City of New York (FDNY) investigators have demonstrated that subgroups of firefighters have developed persistent cough, airway hyperresponsiveness, and/or airways obstruction following their response to the WTC collapse.6-8

Although the acute responses to inhaled irritants are typically dose dependent for most exposed individuals, this is not necessarily true for the chronic effects. Typically, most people who survive acute irritant-induced bronchitis and/or pneumonitis recover without severe long-term respiratory impairment. Some individuals, however, go on to develop asthma or persistent airways obstruction consistent with COPD. Predicting who those individuals will be has been difficult. There is evidence that smoking and atopy are risk factors for chronic respiratory effects of inhalation injury,1,2,9 but clearly many smoking and/or allergic individuals who sustain such injury recover without sequelae. The ability to predict those individuals at greatest risk of developing respiratory impairment after acute airway and lung injury would allow targeting of resources for medical surveillance and early management of respiratory illness.

In this issue of CHEST (see page 412), Nolan and colleagues,10 from the FDNY, report interesting data suggesting that inflammatory biomarkers in blood may have potential for predicting risk of development of respiratory impairment after irritant inhalation injury. Using a case-control design, the investigators show that levels of two proinflammatory proteins, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-derived chemokine (MDC), obtained within 6 months of September 11, 2001, were relatively strongly associated with the development of reduced FEV1 in subsequent years. The risk of having an FEV1 below the lower limit of normal (case definition) was increased two- to threefold with an elevated level of either protein among the 100 nonsmoking firefighters with normal lung function prior to their response to the WTC disaster compared with a control group of firefighters who maintained an FEV1 above the lower limit of normal. Of particular interest, the mean baseline pre-September 11, 2001, FEV1 % predicted value of the case subjects was significantly lower than that of the control subjects, lending credence to the concept that the case subjects represent a subgroup susceptible to lung injury.

Although the findings reported indicate an association between systemic biomarkers and reduced lung function in WTC responders, they do not mean that measurement of GM-CSF and MDC is ready for use in medical surveillance of irritant-exposed populations. There are several limitations to the data reported. First, the results are from a case-control analysis of a relatively small sample size and need to be confirmed in a prospective study design with a larger population. Second, even if confirmed, the sensitivity and specificity of elevated GM-CSF and/or MDC for the prediction of subsequent reduced lung function will need to be determined. The authors used a definition for airways obstruction of FEV1 below the lower limit of normal. Although it is likely that the reduced FEV1 values observed were primarily due to airways obstruction, the report would have been stronger if the analysis included FEV1/FVC values as well. Finally, given that both GM-CSF and MDC are nonspecific biomarkers of inflammation, and specific pathways by which these proteins might cause reduced FEV1 have not been identified, the associations observed in this study should be interpreted with caution. This is especially true because 39 different proteins were measured in the blood of the subjects, giving rise to a multiple comparisons problem.

Limitations aside, this report adds to the impressive body of work that the FDNY research team and their colleagues have produced from their longitudinal follow-up of the WTC responder cohort.4-8 With vision and effort, they have wrought something of value from a tragedy.

References

White CW, Martin JG. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models. Proc Am Thorac Soc. 2010;7(4):257-263.
 
Palmieri TL. Long term outcomes after inhalation injury. J Burn Care Res. 2009;30(1):201-203.
 
Balmes JR. The World Trade Center collapse: a continuing tragedy for lung health?. Am J Respir Crit Care Med. 2006;174(3):235-236.
 
Banauch GI, Hall C, Weiden M, et al. Pulmonary function after exposure to the World Trade Center collapse in the New York City Fire Department. Am J Respir Crit Care Med. 2006;174(3):312-319.
 
Aldrich TK, Gustave J, Hall CB, et al. Lung function in rescue workers at the World Trade Center after 7 years. N Engl J Med. 2010;362(14):1263-1272.
 
Prezant DJ, Weiden M, Banauch GI, et al. Cough and bronchial responsiveness in firefighters at the World Trade Center site. N Engl J Med. 2002;347(11):806-815.
 
Banauch GI, Alleyne D, Sanchez R, et al. Persistent hyperreactivity and reactive airway dysfunction in firefighters at the World Trade Center. Am J Respir Crit Care Med. 2003;168(1):54-62.
 
Weiden MD, Ferrier N, Nolan A, et al. Obstructive airways disease with air trapping among firefighters exposed to World Trade Center dust. Chest. 2010;137(3):566-574.
 
Brooks SM, Bernstein IL. Irritant-induced airway disorders. Immunol Allergy Clin North Am. 2011;31(4):747-768.
 
Nolan A, Naveed B, Comfort AL, et al. Inflammatory biomarkers predict airflow obstruction after exposure to World Trade Center dust.. Chest. 2012;142(2):412-418.
 

Figures

Tables

References

White CW, Martin JG. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models. Proc Am Thorac Soc. 2010;7(4):257-263.
 
Palmieri TL. Long term outcomes after inhalation injury. J Burn Care Res. 2009;30(1):201-203.
 
Balmes JR. The World Trade Center collapse: a continuing tragedy for lung health?. Am J Respir Crit Care Med. 2006;174(3):235-236.
 
Banauch GI, Hall C, Weiden M, et al. Pulmonary function after exposure to the World Trade Center collapse in the New York City Fire Department. Am J Respir Crit Care Med. 2006;174(3):312-319.
 
Aldrich TK, Gustave J, Hall CB, et al. Lung function in rescue workers at the World Trade Center after 7 years. N Engl J Med. 2010;362(14):1263-1272.
 
Prezant DJ, Weiden M, Banauch GI, et al. Cough and bronchial responsiveness in firefighters at the World Trade Center site. N Engl J Med. 2002;347(11):806-815.
 
Banauch GI, Alleyne D, Sanchez R, et al. Persistent hyperreactivity and reactive airway dysfunction in firefighters at the World Trade Center. Am J Respir Crit Care Med. 2003;168(1):54-62.
 
Weiden MD, Ferrier N, Nolan A, et al. Obstructive airways disease with air trapping among firefighters exposed to World Trade Center dust. Chest. 2010;137(3):566-574.
 
Brooks SM, Bernstein IL. Irritant-induced airway disorders. Immunol Allergy Clin North Am. 2011;31(4):747-768.
 
Nolan A, Naveed B, Comfort AL, et al. Inflammatory biomarkers predict airflow obstruction after exposure to World Trade Center dust.. Chest. 2012;142(2):412-418.
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543