To the Editors:
The study by Scott et al. [1] investigated the known association between asthma and obesity with the aim of better understanding the mechanism that drives airways inflammation in these conditions. They enrolled obese and nonobese subjects with asthma and obese and nonobese healthy controls, supposing that obese asthmatics could have a different airway inflammation phenotype compared with nonobese asthmatics. They described an increase in sputum neutrophils in obese asthmatics attributed to the innate immune pathways, while the sputum eosinophils were unaffected by obesity. Furthermore, they reported the highest concentrations of plasma interleukin (IL)-6, C-reactive protein and leptin in obese asthmatic subjects, which confirms that airway inflammation coexists with systemic inflammation in these subjects. Another important finding of this study was the greater percentage of neutrophils, which was especially observed in obese asthmatic females compared with nonobese subjects.
In this regard, although the excess fat remains a potential cause of systemic and local inflammation in asthma, it is now largely known that obesity is one of the main risk factors for obstructive sleep apnoea syndrome (OSAS), a condition that has a similar increase in neutrophilic airways inflammation in its pathogenesis [2]. In their article, Scott et al. [1] found an increase in neutrophilic inflammation mainly in females, a group where the prevalence of OSAS is lower. However, females of perimenopausal age, such as those enrolled by Scott et al. [1], are more susceptible to developing OSAS [3].
The authors of this study completely ignored the possibility that the obese subjects enrolled could also have obstructive sleep apnoea and that it could justify the development of the airways inflammation observed.
Several studies have investigated the association between airway inflammation and OSAS, describing an increase in neutrophils in sputum [2], and high concentrations of exhaled nitric oxide, exhaled carbon monoxide, and other inflammatory markers in the exhaled breath condensate (EBC), such as pH [4], leukotriene B4, tumour necrosis factor-α, IL-6 and IL-8, in subjects with OSAS, especially when obese [4, 5].
Most of these markers correlated with the severity of OSAS and decreased after continuous positive airway pressure therapy, confirming that they are related more to sleep apnoea than to obesity [2]. Our group further showed an increase in intercellular adhesion molecule-1 in the EBC of OSAS patients, attributing the leukocyte migration and sustainment of local inflammation in their airways to this cell adhesion molecule [5].
Furthermore, in support of their hypotheses, Scott et al. [1] showed that body fat may drive airway inflammation in obese asthmatic females, involving an increase in plasmatic leptin in obese asthmatic females. However, as they acknowledge, airway leptin levels might be important to link this obesity to the airway inflammation, but they did not perform these measurements. An increase in leptin in the plasma of obese patients with OSAS compared to obese subjects without OSAS was recently described; this constitutes further proof that the airway inflammation found in obese asthmatics could be due to an overlap in these patients with OSAS rather than to the obesity itself [6]. Although in this study, as in a previous one [7], the percentage of neutrophils was higher than in the control group, they were still in the normal range. These data suggest that the presence of neutrophils is only one aspect of airway inflammation.
Moreover, even if there are not, to our knowledge, any studies that have investigated the relationship between hyperlipidaemia and airway inflammation, we cannot exclude that this could represent another potential factor linking obesity and airway inflammation in asthmatic females.
Another limitation, also recognised by the authors of this study, was that they did not measure the body fat distribution but only considered the body mass index (BMI). As is widely known, obese subjects often present an increase in neck circumference that becomes a high-risk factor for sleep apnoea, and should perhaps always be investigated in obese subjects.
In this regard, the fact that the enrolled population (obese subjects with asthma and also without asthma) was age-, sex- and BMI-matched does not mean that they have the same nocturnal characteristics in terms of respiratory disorders or that these variables are simply the consequence of asthma. Indeed, it is also necessary to consider the conformational alterations of facial skeletons and, particularly, the evaluation of fat distribution, neither of which were assessed in the study by Scott et al. [1]; it is known that the neck circumference, more than weight, is important in causing nocturnal respiratory alterations [8].
In conclusion, we would underline that, although the neutrophilic asthma reported by Scott et al. [1] could be a particular phenotype observed in females with high BMI, as previously suggested both by the European Network for Understanding Mechanisms of Severe Asthma study [7] and Holguin et al. [9], possible clinical consequences of OSAS should also be investigated, especially when the asthma is not well-controlled.
Footnotes
Statement of Interest
None declared.
- ©ERS 2012
