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IS OBESITY ASSOCIATED WITH ASTHMA?

'It is well recognized that both obesity and asthma are major public health concerns, and their prevalence have tremendously increased in many countries over the last decades (1, 2). Although obesity is a known risk factor for type II diabetes and cardiovascular diseases such as hypertension and atherosclerosis, the concurrent increase in the two conditions of obesity and asthma raises the possibility that the two might be linked to each other as suggested by an epidemiologic review of obesity and asthma (3) and by a recent clinical investigation (4).'' '''

Asthma is a complex multi-factorial disease characterized by chronic airway inflammation, bronchial remodeling, reversible airflow obstruction and increased airways responsiveness (5). It affects millions of people worldwide and its prevalence in the United States has doubled in the last twenty years (6) with the greatest increase seen in African American and Hispanics (7). According to Centers for Disease Control and Preventions (8), more than 17 millions of people are affected by asthma, which has increased most rapidly in children who also account for the highest rates of this disease among the population at large. The report also indicates that the prevalence of self-reported asthma for all ages has increased by 74% from 1980 through 1998. Although no national prevalence study on asthma exists in Tunisia, two local teams of Medical Doctors at the health region of Monastir (9) and at the military hospital of Tunis (10) have conducted retrospective investigations on the etiology of chronic diseases. Their data indicate that 31.5% of the observed cases were diagnosed with asthma and diabetes and 40% of the asthmatics were predominately children. Many countries have witnessed large increase in the prevalence of asthma during the last decades, including the United States and Tunisia. The reasons for these increases are not well understood, but may be the result of a complex interplay of genetic, environmental, behavioral and socio-economic factors. Likewise, obesity is suggested to be one factor that may play an import role in the induction, exacerbation or persistence of asthma.

The pathogenesis of obesity is far more complex than a simple imbalance between calorie intake and energy output, but it can be characterized by an excess storage of body fat. Obesity affects as many as a quarter of billion people worldwide, and approximately 100 million adults in the United States are at least overweight or obese (11). Like asthma, the prevalence of obesity has markedly increased in many countries, including the United States (12) and Tunisia (13). For instance, prevalence in US has changed from 13.4% in 1960 through 1962 to 27.6% in 1999 through 2002 among men, and from 15.8% to 33.2% among women (14); one-third of all 16-year-old children are overweight and 15% are obese (5), and prevalence is even greater in some minority groups (11). Data from Tunisia exhibit similar disturbing trends, with alarming obesity rates exceeding 22% in women but only 7% in men (15). The prevalence of obesity has been rising since 1980, and while the rate has increased significantly from 8.7% in 1980 to 22.7% in 1997 in women, it has remained low in men (15). Overweight is on the rise for both sexes attaining alarming levels of 50.9% and 30.3% in women and men, respectively (15, 16). Furthermore, overweight increases with age, and the risk of obesity among Tunisian adolescents is 9.5% in girls and 5.1% in boys (15). Ironically, one key factor that may explain the rise in obesity is the economic progress that Tunisia has been witnessing since its independence from France in 1956, and its rapid development over the last two decades. For example, economic indicators show that while the rate of poverty had dramatically dropped from 50% in 1956 to 3.9% in 2005, the individual annual revenue of a Tunisian had increased from 91 dinars to 3803 dinars, and there has been a ten-fold increase in the food supply during the same period of time (17). Although this economic prosperity allowed the population to afford more energetic food products, the consumption habits of individuals is certainly related to their socio-economic situation. For example, the consumption of processed foods and fast foods may have contributed to the increase of obesity and overweight in the United States and in Tunisia (and probably in many other countries).

Obesity and Asthma: Besides being a risk factor for type II diabetes, heart disease and some forms of cancer, obesity may also have adverse effects on airway hyper-responsiveness as well as on the onset of asthma. In addition to epidemiologic studies indicating an increased prevalence of asthma in the obese (18-21), some investigators have proposed immunological and inflammatory mechanisms (22, 23) as well as mechanical mechanisms (24, 25) by which obesity could interact with asthma. For instance, adipose tissue produces and releases two hormones, leptin and adiponectin, that exert pro-inflammatory (26) and anti-inflammatory roles (27), respectively. Interestingly, serum leptin is known to markedly increase in obesity (28, 29) and is found at higher levels in asthmatics than no-asthmatics (30) regardless of the extent of obesity. In contrast, serum adiponectin levels have the tendency to be reduced in obese subjects (31). Changes in airway structure and function have been also associated with obesity (23). For example, increased abdominal and chest wall mass in the obese individuals causes reduced functional residual capacity (FRC) (32), a major determinant of airway diameter (33). Consequently, it is likely that obesity-related changes in FRC unload the airway smooth muscle cells thereby allowing them to shorten excessively when activated.

Investigation of the Association: Collectively, there is mounting evidence that obesity is a major risk factor for asthma. Therefore, investigating the mechanism governing the relationship between obesity and asthma incidence and the role of weight management among patients with lung disease have important ramifications for the prevention and treatment of both conditions. To this end, a recent clinical investigation (4), supported by a Fulbright Award, has been conducted at the Medical School of Sousse (Tunisia) to determine whether obesity of women is associated with hyper-reactivity.

While several classifications and definitions exist for degrees of obesity, the most widely accepted international criteria are based on body mass index (BMI=body weight/height2). For adults, in particular, the World Health Organization (WHO) defines overweight as a BMI of 25-29 kg/m2, and obesity as a BMI of at least 30 kg/m2. Accordingly, subject population of this study consisted of adults who were grouped into three categories, with equal number of subjects, according to the following BMI ranges: BMI (normal weight) < 25 kg/m2; 25 kg/m2 ≤ BMI (overweight) < 30 kg/m2; BMI (obese) ≥ 30 kg/m2.

A total of 160 women (63 obese, 45 overweight and 52 lean subjects) were recruited from Sousse and its suburban small towns by word and mouth. Only females were included in this study because, unlike women, the large majority of men are heavy smokers. Before they were admitted in the study, all participating subjects had undergone health screening and medical examination as well as physiological measurements. Those who were included in the study were healthy (no high blood pressure, no medical history of asthma, no chronic respiratory, heart or any other diseases) and never smoked cigarettes. After the health screening, each subject underwent pulmonary function testing prior to inhaling aerosolized methacholine (MCH) (for baseline), and after administering this cholinergic agonist (challenge for bronchocontriction). The most important pulmonary function parameters were determined by spirometric measurements; they included forced expired volume in one second (FEV1), forced expired flow between 25% and 75% of the vital capacity (FEF25-75) and forced vital capacity (FVC).

The Data indicate that: 1) there were significant differences in all the pulmonary function parameters (FEV1, FVC and FEF25-75) between the obese and lean groups as well as between the overweight and the lean groups; 2) the mean maximum fall of FEV1 in response to MCH challenge was significantly higher for the obese group (12%) than for the overweight (10%) or the lean (6%); and 3) the efficacy of the MCH agonist promoting the maximal response (Emax) and its potency or effective dose (ED50) producing 50% of the maximal response were both associated with BMI (the higher the BMI, the higher the Emax and the lower the ED50).

In conclusion, the results of this investigation clearly show that obesity affects pulmonary function performance in Tunisian women by potentially promoting either bronchial hyper-reactivity or asthma.

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