Obesity is an increasingly frequent condition associated with increased adipose, systemic and pulmonary inflammation. There is an emerging and unexpected finding that obese individuals may not be at a greater risk for ARDS and, indeed, may even be partially protected against ARDS. This finding is known as the Obesity-ARDS Paradox. In this review we discuss the observations regarding this intriguing phenomenon and begin to elaborate on the theoretical rationale that obesity-triggered low-grade inflammatory processes may constitute pre-conditioning insults or trigger anti-inflammatory adaptive mechanisms that confer protection against ARDS. The Obesity-ARDS ParadoxObesity is an increasing global epidemic that increases cardiovascular abnormalities, diabetes, sleep apnea and mortality [1][2][3]. The Acute Respiratory Distress Syndrome (ARDS) is a highly fatal respiratory failure disorder [4,5]. Because both obesity and ARDS are characterized by increased inflammation and oxidative stress [6][7][8][9][10][11][12], obesity might reasonably be considered a risk factor for ARDS. However, the opposite seems to be the case. Although obese patients manifest a greater incidence of certain pro-inflammatory respiratory diseases, such as sleep apnea and asthma [13,14], they actually have a lower than expected incidence and/or severity of ARDS in a number of studies (Table 1) [15][16][17][18][19][20][21]. This unexplained finding is termed the "Obesity-ARDS Paradox. " Some of these studies are retrospective in nature or do not allow the investigation of the concept that has been termed "Metabolically Healthy Obesity" (MHO) [22,23] terminology that refers to obese individuals with no associated metabolic comorbidities (insulin resistance, atherosclerosis, liver dysfunction). Interestingly, this MHO concept has been linked to lower adiposerelated inflammatory profiles and a lower mortality risk compared to individuals with metabolically unhealthy obesity [24]. How obesity may affect systemic and even pulmonary inflammatory responses is the key focus of this review. The differences in the metabolic and inflammatory backgrounds of patients in studies that do not fully support the Obesity ARDS Paradox phenomenon may explain their different conclusions. However, the finding of multiple studies showing a lower-than-expected mortality (including lower mortality [15,19,20] or similar mortality [17,18,21] than normal weight patients) in obese individuals after ARDS is provocative. Elucidating the causes of this observation should increase understanding of the causes of ARDS and, perhaps, lead to new and needed therapeutic approaches. Pre-Conditioning as a Mechanism Contributing to the Obesity-ARDS ParadoxThe underlying mechanism responsible for the Obesity-ARDS Paradox is unknown. Confronted with trying to elucidate a reason, we hypothesized earlier [25] that obesity-induces a low-grade inflammation that generates a process that subsequently protects the lung against later insults. We termed this protective response the "pre-co...
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