Assessing Inflammatory and Behavioral Pathways Linking PTSD to Increased Asthma Morbidity in WTC Workers

SIGINIFICANCE: Importance of the Problem: Multiple studies have shown a high prevalence of asthma in WTC rescue and recovery workers, local residents, and passersby. Using data from the National Health Interview Survey (NHIS), the researchers found that WTC workers have twice the risk of asthma compared to the general United States (US) population. Data from the WTCHP shows a 28% cumulative incidence of asthma 9 years after September 11, 2001 among WTC workers. These studies show that asthma is the most prevalent respiratory condition among WTC rescue and recovery workers.

WTC workers with asthma include individuals with prior history of the disease and new cases of irritant-induced asthma. Many workers with preexistent asthma developed worsening symptoms after WTC-related exposures (WTC-exacerbated asthma). Other workers developed new asthma symptoms without latency during or after WTC exposure and were diagnosed with irritant-induced asthma. Multiple cases of new onset asthma among WTC workers have been reported in the years following exposure to the WTC site; characterization of these cases has been more difficult. Despite this potential heterogeneity, these conditions are frequently grouped in clinical practice as WTC-related asthma and managed similarly.

Studies found substantial burden of asthma morbidity in WTC workers and exposed community members, with reports of poorly-controlled in 34% and very poorly-controlled symptoms in 35% of exposed individuals. Increased risk of emergency department (ED) visits and hospitalizations as well as poor quality of life in WTC workers with asthma have been reported, showing a major impact on health.

Scientific Premise of Project: PTSD is Associated with Increased Asthma Morbidity in WTC Workers: Prevalence of psychological symptoms in WTC-exposed populations is high; with PTSD reported as the most common (~30%) mental health condition. Studies have also found high rates (25-35%) of PTSD comorbidity in WTC workers with asthma. Mental health conditions and PTSD in particular, have been associated with increased asthma morbidity. The researchers found that WTC workers with PTSD had worse asthma control, increased healthcare use, and poorer quality of life (see preliminary data). Similarly, a study of WTC workers indicated that severity of PTSD symptoms predicted new onset and worsening of asthma. Data from studies in the general population have also shown that PTSD is associated with higher asthma morbidity. In summary, studies have documented a high level of overlap between asthma and PTSD in WTC workers and other exposed populations and have documented that PTSD is a major contributor to increased asthma morbidity. However, the underlying mechanisms explaining this relationship remain unknown.

Potential Biological Pathways Linking PTSD and Asthma Morbidity: The impact of PTSD extends to multiple organ systems as a consequence of changes in the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system.These PTSD-associated systemic alterations may impact asthma morbidity. PTSD is associated with a basal low-grade systemic inflammation, in particular, increased plasma levels of pro-inflammatory cytokines such as interleukin (IL)-1α, IL-2, IL-6, tumor necrosis factor-alpha (TNF-α and decreased IL-4, IL-5 ("Th2-cytokines"). Airway inflammation, a central feature of asthma, may be modulated by enhanced systemic inflammation as that observed in PTSD. Major asthma endotypes, which describe asthma subtypes based on inflammatory mechanisms, include allergic, intrinsic (non-atopic), and noneosinophilic asthma. Allergic asthma is characterized by airway eosinophilia driven by TH2-dominant inflammation. Noneosinophilic asthma is characterized by airway neutrophilia has been associated with refractory disease, severe exacerbations, and increased risk of intubation. Key cytokines driving neutrophilic asthma include IL-1β, IL-6 and IL-17, which are elevated in patients with PTSD.51 IL-6 directs and stabilized T-cells towards a Th17 subset, which can then recruit and activate of neutrophils. Therefore, systemic inflammatory changes associated with PTSD, may worsen asthma outcomes by driving a neutrophilic asthma phenotype. Identification of the biological pathways underlying worse asthma in patients with comorbid PTSD has important implications for disease management including indications for inhaled corticosteroids (ICS) and new biological drugs and may offer new alternative targets for therapy.