Asthma diagnosis and treatment
Does obesity weigh heavily on the health of the human airway?

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Strength of association

A strong association, such as a 5- to 10-fold increase in risk, as is seen between cigarette smoking and lung cancer, is more likely to be causal than a weak association. A weak association is more likely to be spurious, arising from bias, confounding, or chance, although it does not rule out causality. The association between asthma and obesity is modest, with measures of relative risk described ranging from 1.5 to 3.0 in most studies, which raises concerns that it might not be causal.

Consistency of association

If the association is repeatedly observed in different populations in different settings, it is more likely to be causal than an isolated observation. The obesity-asthma association has been observed in both children and adults, in various races and ethnic groups, as well as in different parts of the world. In most studies asthma was clinically defined as a physician diagnosis of asthma, presence of asthma symptoms, use of asthma medications and hospitalizations, or emergency department visits

Specificity of association

This relates to a single cause leading to a single effect. This might be a holdover from infectious disease thinking and does not necessarily apply to complex disease traits, such as asthma (which more often than not have multifactorial causation). Such effect specificity is clearly lacking in this association because obesity has also been shown to cause various diseases other than asthma, such as Type II diabetes mellitus and coronary heart disease.

Temporality of association

This postulates that a cause must precede an effect in time. It was previously argued that asthma leads to physical inactivity and subsequent weight gain and obesity. Several prospective studies have now found a positive association between weight gain and subsequent development of (incident) asthma, thereby providing considerable support for the thesis that obesity in fact antecedes the development of asthma.7

Biologic gradient

The presence of a dose-response gradient (ie, more of a dose leads to more of an effect) supports the idea of causality. A modest dose-response relationship has in fact been described in various studies whereby the risk of asthma increases with the severity of overweight-obese status. However, several studies have also described another interesting observation that the association between BMI category and asthma risk might have a U- or J-shaped curve whereby the underweight category (or those

Plausibility of association

According to this postulate, the idea of causation must be biologically plausible. A host of mechanistic pathways have been suggested to explain this association, and these are summarized in Fig 1.8, 9, 10 However, these pathways might not be mutually exclusive, and the dominant mechanism among them is yet to be singled out.10 Some believe that asthma-like symptoms in obese patients might be due to reasons other than BHR, such as increased work of breathing associated with thoracic restriction,

Coherence of association

The idea of causation must accord with other relevant observations. For instance, there is at least one article examining data from the National Health and Nutrition Examination Survey that suggests that unadjusted prevalence of atopy increases significantly with increasing obesity.11

Experimental evidence for association

Supporting data for this association from animal experiments are limited. Fredberg and Shore,10 in their review in this journal, have quite rightly commented that “the majority of studies published on this topic are epidemiological investigations; the paucity of basic research on the possible role of adipose tissue in modulating asthma susceptibility and symptoms is quite striking.” It has now been shown that ozone-induced BHR and airway inflammation in mice that are obese (ob/ob) is higher

Analogy

Like obesity, other environmental factors are also associated with asthma. An example of such a factor is the popular hygiene hypothesis that has been described in the rostrum by Platts-Mills.15 This hypothesis proposes that decreased exposure to infections, decreased exposure to farm animals-endotoxin, or increased antibiotic use in early life results in dominance of TH2 responses, which might also partly explain the increase in asthma prevalence.

So is the association between obesity and

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Disclosure of potential conflict of interest: A Sood has consultant arrangements with Wyeth-Ayerst and GlaxoSmithKline; has received grants–research support from the American Lung Association; and is on the speakers' bureau for Actelion Pharmaceuticals.

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