Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the U.S. and a major cause of long-term disability. While cigarette smoking is the probable cause of COPD in the majority of cases, it has been estimated that about 15% of COPD in the overall population may be due to occupational exposures, and a much higher portion of COPD among non-smokers may be due to occupational exposures [Hnizdo et al., 2002]. Firefighters, both municipal (structural) and wildland are known to face respiratory hazards [Musk et al., 1979; Chia et al., 1990; Materna et al., 1992; Scannell and Balmes, 1995; Bergstrom et al., 1997; Burgess et al., 2001; Prezant et al., 2002; Greven et al., 2012]. Researchers have identified particulates and other exposures, heavy physical exertion and cardiovascular strain to be among the chief, nontraumatic health hazards associated with structural firefighting [Guidotti and Clough, 1992; Austin et al., 2001; Fahy, 2005].

Various studies have associated increased serum concentrations of C-reactive protein (CRP), a chemokine, primarily synthesized in the liver but also produced in the respiratory epithelium [Gould and Weiser, 2001], to reduced lung function in healthy populations [Mendall et al., 2000; Cirillo et al., 2002; Mannino et al., 2003; Aronson et al., 2004; Kony et al., 2004; Gan et al., 2005; Walter et al., 2008; Thorleifsson et al., 2009]. Kony and coworkers studied serum CRP levels, forced expiratory volume in 1s (FEV₁), and bronchial hyperresponsivesness (BHR) as measured by methacholine challenge, in 259 adults free of cardiovascular disease or respiratory infection. The authors observed that the mean FEV₁ (adjusted for potential confounders such as age, gender, height and smoking status) was lower in subjects with a high CRP level and BHR was more frequent (41.9% vs. 24.9%) in these individuals than in subjects with lower CRP levels [Kony et al., 2004]. Additionally, Aronson et al. [2004] also observed a strong inverse association between CRP levels and quartiles of FEV₁ as well as forced vital capacity (FVC).

Data collected in the Third National Health and Nutrition Examination Survey (NHANES III) also found associations between increased CRP level and reduced pulmonary function [Cirillo et al., 2002; Mannino et al., 2003; Gan et al., 2005]. Moreover, when Gan et al. [2005] focused on smoking status, the authors observed an additive effect of current smoking on the inverse relationship of CRP, FEV₁ observed previously in this cohort. Similar results were recently observed in a cohort of FDNY World Trade Center disaster first responders [Weiden et al., 2013]. The authors report that individuals with elevated CRP levels obtained within 6 months of 9/11/01 had a significantly increased risk of developing decreased lung function (FEV₁) at their subsequent pulmonary testing, independent of a history of CVD. Two case–control studies of both childhood and adult asthmatics also found increased CRP levels correlated with decreased pulmonary function in steroid-naive participants [Takemura et al., 2006; Deraz et al., 2012]. Takemura and coworkers additionally observed a strong correlation between sputum eosinophils and CRP levels in adult asthmatics, however this was not observed in children [Deraz et al., 2012], possible reflecting the differences in disease etiology.

Genetic studies to date of hsCRP polymorphisms or haplotypes have yielded inconclusive results [Yanbaeva et al., 2009; van Durme et al., 2009; Bolton et al., 2011]. Specifically, while both Bolton and van Durme observed strong inverse associations between CRP and lung function, neither study was able to identify a CRP polymorphism or haplotype associated with pulmonary dysfunction. Thus, while the association has been described in the literature, the mechanism remains unclear.

We hypothesized that hsCRP as a biomarker of systemic inflammation may indicate reduced lung function in structural firefighters.

Characteristics of the population are summarized in Table I. Complete data were available for 401 individuals. Participants had a median age of 36 years. Sixteen (4%) reported a history of pulmonary disease (e.g., asthma and or chronic bronchitis) and 16 (4%) reported active pulmonary disease. One participant reported a history of heart disease. We did not record information on race/ethnicity; however, we know that fire departments where our subjects work are 85–90% White, as previously documented [Poston et al., 2011].

Lung function declines, specifically FEV₁, are established risk factors for CVD, rivaling that of cholesterol [Sin et al., 2005]. Similar to other studies, we observed an inverse relationship between higher hsCRP and lung function as measured by FEV₁%-predicted and FVC%-predicted, after adjusting for established potential confounders. Unlike Gan et al. we did not observe an additive effect of current smoking onFEV₁%-predicted in our cohort. However, given the limited number of subjects currently smoking, we may not have had sufficient statistical power to observe such a difference.

While numerous studies have found a negative association between lung function reduction and increasing CRP, the mechanism remains unclear. Genetic studies to date of hsCRP polymorphisms or haplotypes have not helped elucidate the mechanism [Yanbaeva et al., 2009; van Durme et al., 2009; Bolton et al., 2011]. In the absence of definitive genetic studies some researchers have suggested reverse causality [Bolton et al., 2011] or an undefined mediator between lung function and CRP may be driving the association between the two outcomes. CRP has also been linked to the development of ischemic heart disease and stroke, the two primary causes of death in individuals with COPD. Higher levels of systemic inflammation may simply represent spill over from inflammation in the airways. Concurrent examination of systemic inflammation, eosinophilic and neutrophilic, from induced sputum, in this population may assist in answering this question.

As previously noted, CVD events are the leading cause of morbidity and mortality in structural firefighters affecting 1 in 1,000 structural firefighters annually [Fahy, 2005; Soteriades et al., 2011]. Higher BMI and lower cardiorespiratory fitness, as measured by achieved MaxMETs are among the factors associated with an elevated CVD risk profile in firefighters [Baur et al., 2011]. We observed a borderline significant association between higher cardiorespiratory fitness, as measured by achieved MaxMETs and higher FEV₁%-predicted values but not vital capacity. We observed an association between higher FEV₁%-predicted and higher BMI and an inverse relationship between higher FEV₁%predicted and resting systolic blood pressure after adjusting for hsCRP and MaxMETS.

There is evidence that particulate matter (PM) produced by fires may be more toxic than PM from ambient air due to chemical components found in the smoke [Wegesser et al., 2009]. Leonard et al. [2007] examined six sets of aerodynamically size-selected aerosol samples at a large fire. The authors found smoke particles in all size fractions, with highest overall mass fraction on filters in the fine range. Ultrafine particles (<0.1μm diameter) may produce greater inflammation than larger particles, simply due to a much larger total surface area to volume ratio of the former. Ultrafine particles may escape phagocytosis by alveolar macrophages, easily gaining access to the pulmonary interstitium. The severity of airways inflammation due to particulate exposures is correlated with particle surface area [Brown et al., 2001; Oberdorster, 2001].

Additionally, smoke particulate may be associated with adverse respiratory health outcomes as a result of the generation of toxic free radicals [Bankson et al., 1993; Jankovic et al., 1993; Leonard et al., 2000]. Leonard et al. [2007] used electron spin resonance to measure carbon-centered as well as hydroxyl radicals produced by a Fenton-like reaction with smoke. The authors observed that OH radical precursors were more prevalent (per unit mass) in the ultrafine-sized particles and caused a significant increase in cellular H₂O₂ production, DNA strand breaks, and reactive oxygen species (ROS)-induced lipid peroxidation as measured by malondialdehyde (MDA). Thus, exposure to chemicals and fine particulates routinely encountered during structural firefighters overhaul operations, where respiratory protection is generally not donned [Burgess et al., 2001] could generate ROS, potentially leading to oxidative damage and inflammation and may explain the increased risk of lower lung dysfunction in this healthy worker population comprising primarily non-current smokers. Moreover, Weiden et al., observed a significant inverse association between CRP and FEV₁ in firefighters exposed to PM generated by the World Trade Center Disaster [Weiden et al., 2013]. The authors hypothesized that the increased systemic CRP levels could reflect pulmonary vessel damage. It is of note, that some of the mean predicted values for lung function we observed were lower than the referent population. However, our study lacked a means to quantify this type of exposure Further research is needed to examine how our findings might relate to exposure.

We examined hsCRP which minimizes the biological variation in the samples. Only obtaining one measure of hsCRP, which varies by season [Sung, 2006], could have affected our results. However, the testing took place over the course of a few years year so any potential misclassification would be non-differential.

We did not observe a difference among individuals with a history of pulmonary or cardiovascular disease. However, given the small number of individuals with these outcomes, 16 and one respectively, we may have lacked sufficient statistical power to observe one if it did exist.

Our study has a number of limitations. We examined only one biomarker of inflammation. Future studies should examine sputum biomarkers of neutrophilic inflammation, such as myeloperoxidase, which has been linked to occupationally-related airways obstruction [Jung and Park, 1999]. We do not have exposure data on participants which limited our ability to examine dose–response relationships. Moreover, we lack lower respiratory symptom data such as wheeze and shortness of breath, which limits the interpretation of our objective findings as they relate to overall well-being and function. Finally, our study population (n = 401) with complete data that was analyzed constituted 98% of the male members of the fire department who consented to participate. While the possibility of selection bias does exist, we do know that our consented population has a very similar age, BMI, and expected ethnic composition to that found in a randomly sampled, population-based study of career firefighters [Poston et al., 2011].

hsCRP, a biomarker of systemic inflammation potentially generated from lifestyle and occupational exposures including smoke particulate, is associated with diminished exercise tolerance and oxidative stress. Damage reflected in elevated HsCRP may result in reduced lung function in structural firefighters. Our results corroborate the findings of an inverse relationship between CRP and lung function observed in both occupational settings and the general population. The long-term significance of these findings to the cardiopulmonary health of structural firefighters, including the relationship to exposure, should be investigated further.