Body Composition and Pulmonary Diseases

aJohn Ochsner heart and vascular institute, Ochsner Clinical school, the university of Queensland school of medicine, new Orleans, la, usa; bDepartment of Physiology, faculty of medicine, university of valencia and inCliva biomedical research institute, valencia, spain; cuh Center for Cardiovascular Prevention and Center for integrated and novel approaches in vascular-metabolic Disease (Cinema), harrington heart and vascular institute. university hospitals Cleveland medical Center. Case Western reserve university school of medicine, Cleveland, Oh, usa

Obesity has clearly reached near epidemic levels in the United States and much of the Westernized world [1][2][3]. In fact, recent statistics suggest that 75% of the US population are now either overweight or obese, and 42% meet the current body mass index (BMI) criteria (BMI ≥ 30 kg/m 2 ) for obesity, and even more concerning is that now 9% of US adults meet criteria for severe, class III, or morbid obesity (BMI ≥ 40 kg/m 2 ) [1]. Obesity certainly places a "heavy" toll on overall health of the US and Westernized world population and our healthcare systems [2]. Obesity adversely impacts cardiovascular diseases (CVD) by worsening almost all the CVD risk factors, including increasing levels of arterial pressure, increasing plasma glucose levels, thus leading to metabolic syndrome (MetS) and diabetes mellitus (DM), worsening lipids, especially triglycerides, and increasing systemic inflammation. Not surprisingly, almost all CVD is increased with obesity, including hypertension, coronary heart disease (CHD), heart failure (HF), and atrial fibrillation (AF). As we reviewed elsewhere regarding the impact of obesity in COVID-19 [3], obesity is also associated with more renal diseases, increased risk of coagulation and musculoskeletal abnormalities and premature disabilities, venous thromboembolism and pulmonary embolism (PE), among other respiratory diseases [4]. Nevertheless, despite the increased health risks associated with obesity, we have focused considerably on the "obesity paradox" among patients with CVD, where generally overweight and obese with CVD have a better short-and medium-term prognosis than do leaner patients with the same CVD [2,3,5]. Understanding this in underweight who generally have a higher mortality in most diseases is not surprising, and this is certainly the case in most CVD. However, understanding why overweight and obese have a better prognosis than do the patients with "normal" BMI is more difficult, which has been demonstrated in numerous studies and large meta-analyses. Possible explanations for this paradox include heavier patients having higher muscle mass, fitness, and more metabolic reserves, among other mechanisms. This obesity paradox has also been noted in end-stage renal disease [6], as well as pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and PE, as well as complications from infections, including pulmonary infections [7,8].
In this issue of the COPD, Journal of Chronic Obstructive Pulmonary Disease, Zhang et al. [9] used the National Health and Nutrition Survey (NHANES) to assess the impact of BMI and abdominal obesity on pulmonary airflow obstruction in 12,865 Americans aged 20-80. Although overweight and obesity were associated with reduced risk of airflow obstruction, abdominal obesity was associated with a 41% increased risk of airflow obstruction in the fixed ratio method but not by the lower limit of the normal method. These results potentially suggest discordant effects of BMI and central obesity on airflow obstruction.
As mentioned above, other studies have also suggested an obesity paradox with COPD [7,10,11]. In a meta-analysis of 22 studies in 21,150 participants, overweight and obesity were associated with 53% and 41% reductions in mortality, respectively [10]. In a study of 744 Moroccan adults, obesity by BMI and central obesity, determined by waist circumference (WC), were associated with mortality reductions, especially in women [11]. Besides COPD, as mentioned above, an obesity paradox has been noted for PE and infections [8,12,13]. Although there seems to be a paradox in pulmonary diseases, these results underline how important regular exercise in underweight individuals is to counter the side effects of malnutrition and help maintain muscle tone and muscle strength, which may be particularly important for respiratory muscles. In effect, as with CVD, physical activity (PA) and cardiorespiratory fitness (CRF) may be a major reason for the "obesity paradox," and PA/CRF may markedly alter the relationship between adiposity and subsequent clinical outcomes [2,[14][15][16][17]. However, it should not be discounted that asthma may be a condition where obesity has adverse effects on lung volumes and disease severity, including airway hyperresponsiveness and reduced response to various treatments, [18] and the article in this issue [9] raises the possibility that this may be even more compromised with abdominal obesity.
Currently, we remain in the COVID-19 era, and considerable evidence suggests that obesity may adversely affect clinical outcomes [3,[19][20][21]. Although some of this may be due to the association of obesity with co-morbidities, such as MetS/DM, hypertension, HF, AF, CHD and renal disease, all of which are associated with worse COVID-19 outcomes (Figure 1), obesity may have some direct respiratory effects to worsen COVID-19 outcomes [3]. There are many reasons why respiratory abnormalities in obesity may worsen COVID-19 outcomes, including restrictive lung disease, reduced ventilation and lower oxygen saturation levels. Additionally, the site of the coronavirus entry into the cells is at the angiotensin-converting enzyme 2 receptor (ACE 2), and adipocytes have even more ACE 2 receptors than does the lung, so increased fat could serve as a reservoir for increased coronavirus in humans [3,19,22].
Not only general obesity, but specifically central or abdominal obesity, more so than MetS, seem to be associated with clinical deterioration, especially respiratory distress, in COVID-19 [23]. Increased abdominal obesity compromises pulmonary function in supine patients by decreased diaphragmatic excursion, while the base of the lung ventilation is also impaired, resulting in reduced oxygen saturated blood levels [24]. Thus, it has been reported that abdominal adiposity represents a more significant risk factor for respiratory distress in COVID-19 patients [23]. Likewise, obesity impairs immune function and provokes chronic inflammation by increasing B cells in visceral adipose tissue and producing autoreactive immunoglobulins [25].
It is essential to underline that the discordant relationship between high BMI and high WC and airflow obstruction needs to be further verified by large-scale prospective studies. Additionally, it would be informative to validate the article's findings using more detailed metrics of lung function, including lung volumes, DLCO, etc., with future studies. Finally, despite obesity paradoxes, in a perfect world all individuals would benefit from maintaining high PA and CRF and maintaining ideal body weight throughout the lifespan from childhood to old ages. This is not happening in our present society, when many gain weight and lose PA and CRF with aging [2]. Higher PA and CRF may be associated with increased immunity and better prognosis against lung diseases and COVID-19 [26][27][28][29]. Despite paradoxes in lung diseases, great efforts are needed to reverse these trends, especially for CVD and cancers.

Disclosure statement
The authors declare that they have no competing interests.