The Brazilian Ministry of Health1 research shows that 54% of the Brazilian population over 18 years old are overweight, 57.3% of men and 51.2% of women. The World Health Organization2 shows that in 2016 more than 1.9 billion adults (39%) were overweight and more than 650 million (13%) were obese.

The adipose tissue, being an endocrine organ, secretes adipokines and influences the release of inflammatory mediators and such substances contribute to a low grade systemic inflammation state and can promote directly or systemically changes in pulmonary function.3–5 Increased adipose tissue may also influence the susceptibility to lung infections, increased lung inflammation with environmental exposure, and airway obstruction exacerbation in preexisting lung diseases.6

Beuther et al.7 observed in a meta-analysis that the obese individual is more likely to develop asthma in comparison to eutrophic, and in Melo et al.8 study, asthma prevalence in the obese population was 18.5% in a sample of 363 obese, and in Baltieri et al.9 study, asthma prevalence was 4.6% in a sample of 4791 obese.

In view of the vast metabolic and inflammatory changes that accompany the obese individual, altered pulmonary function is evident in many studies, both by inflammatory and mechanical origin. Studies have therefore shown lung function alteration in the obese individuals without associated prior disease, such as the mechanical changes caused by adipose tissue deposition around the thorax and abdomen, which include reduction of Expiratory Reserve Volume (ERV),10 and may cause areas of atelectasis, especially in the pulmonary bases.11,12 In addition to inflammatory alterations, inflammatory cytokines act on the lung which causes lung function impairment. Such changes are evidenced in the literature by the reduction of Forced Expiratory Volume in the First Second (FEV1), Functional Residual Capacity (FRC), Forced Expiratory Flow in 25–75% (FEF25–75%) and increase in FEV1/FVC (Forced Vital Capacity) ratio.5,13,14

Thus, the aim of the present study was to correlate adipokines levels and inflammatory mediators with lung function in individuals with obesity and bronchial asthma symptoms.

This is a cross-sectional study conducted at a training hospital, approved by the Research Ethics Committee, registered in the Brazil Platform and with Research Support from the Foundation for Research Support of the State of São Paulo (FAPESP).

We analyzed 80 women who entered the program and the patients who answered the ACT questionnaire to check asthma control 40% had a score greater than or equal to 18 and were classified as “controlled asthma”. The data of the characteristics of each group based on the ACT score are described in Table 1. Of the patients studied, 19.1% had grade II obesity and 80.9% had grade III obesity.

Fig. 1 characterizes the values obtained from the pulmonary function variables of the sample studied, described as a percentage of the predicted value in the literature of each group based on the ACT score. For the group classified as “controlled asthma” (ACT≥18) 56.25% of the patients obtained values above 80% of that predicted in FVC versus 50% of the group classified as “non-controlled asthma” (ACT<18). For FEV1, 53.1% vs. 37.5%; FEV1/FVC 87.5% vs. 72.9%, PEF 34.3% vs. 22.9% and FEF25–75% 56.2% vs. 29.12% respectively.

Figure 1.

Box plot of spirometric variables in percent of predicted of each group based on the ACT score.

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The data obtained from the Spearman correlation between adipokine levels and inflammatory blood and pulmonary sputum mediators with spirometric variables of group classified as “controlled asthma” (ACT≥18) are expressed in Table 2 and Fig. 2. And between adipokine levels and inflammatory blood and pulmonary sputum mediators with spirometric variables of group classified as “non-controlled asthma” (ACT<18) are expressed in Table 3 and Fig. 3.

Figure 2.

Group classified as “controlled asthma” (ACT≥18): Scatter plot between sputum IL-6×FVC (r=−0.425; p-value=0.027); sputum IL-6×FEV1 (r=−0.423; p-value=0.028); and between blood CRP×FEV1/FVC (r=0.400; p-value=0.039); blood IL-8×PEF (r=−0.497; p-value=0.008).

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Figure 3.

Group classified as “non-controlled asthma” (ACT<18): Scatter plot between sputum TNF-α×FVC (r=0.315; p-value=0.045); sputum IL-6×FEV1 (r=−0.358; p-value=0.034); sputum IL-6×FEF25–75% (r=−0.354; p-value=0.037).

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We observed that 60% of the patients did not have controlled asthma in relation to symptoms, medication use and impact on daily activities, directly reflecting on the pulmonary function measurements, with more than half of the patients in this group obtaining measures of FEV1, PEF and FEF25–75% below and 80% of predicted levels. Such measures represents the permeability of small pathways24 and the examination of lung function together with patient's symptomatology and a good clinical evaluation contributes to the pulmonary diseases diagnosis, such as asthma. Epidemiologically, about 300 million individuals are affected by asthma in the world. According to the World Health Organization,25 it is estimated that 235 million people worldwide suffer from asthma. It is a global public health problem, but more than 80% of deaths occur in low and middle-income countries.

The presence of asthma symptoms can cause quality of life impairments, mainly related to environmental stimuli and activity limitation and worse classifications of quality of life is associated with worse FEF25–75%.26

Since adipose tissue is an endocrine organ, the obese individual may present a low-grade systemic inflammatory condition that can affect several organs, including the lungs. Such inflammation may lead to narrowing, airflow obstruction, and premature closure of small airways,3–5,27 causing asthma symptoms.

Bronchial hyperresponsiveness to an inhaled antigen can lead to an inflammatory cascade of airways and degranulation of mast cells, activation of T cells and alveolar macrophages, cytokine production, and recruitment and activation of eosinophils in the airway, resulting in epithelial scaling.28 In view of this, all mechanical and inflammatory changes in the lungs of morbidly obese individuals may lead to changes in the permeability of the smaller airways, reflecting FEV1, PEF and FEF25–75%.13

Thus, the treatment of these patients should involve therapy for weight loss and symptomatic respiratory improvement. There is evidence that weight loss improves levels of inflammatory mediators and adipokines in individuals with grade II and III obesity culminating in better asthma control.9

Most of the studies evaluated by Gupta et al.29 study adipokines, such as adiponectin and leptin, as triggers of the inflammatory alterations found in obese individuals, and the proinflammatory action of leptin is structurally homologous to IL-6 and increases chemotaxis and phagocytosis, leads to cell proliferation T that modulates cytokines and favors the Th1 response rather than Th2. Leptin levels increase in proportion to the increase in BMI.30 On the other hand, adiponectin has anti-inflammatory action and inhibits the production of some inflammatory cytokines such as IL-6 and TNF-α.29

In the present study, there was a significant negative correlation between IL-6 in the sputum with FVC and FEF25-75% in the group ACT<18 and with FVC and FEV1 in the group ACT≥18. The higher the number of pulmonary IL-6, the worse the spirometric values were. The Peters et al.31 study suggests a role for plasma IL-6 in systemic inflammation as a measure of disease severity in an asthmatic patients, as well as an association between increased IL-6 and worse FEV1 in obese individuals.

There is evidence that IL-6 is also related to visceral obesity and adiponectin with subcutaneous obesity in asthmatic women. Visceral obesity is associated with poorly controlled asthma and poor lung function, as well as increased levels of IL-6.32

The present study also found a negative, significant correlation between the blood concentration of IL-8 with PEF in ACT≥18 group. Alveolar macrophages of obese subjects with asthma produce higher amounts of IL-8 and TNF-α after leptin stimulation than macrophages of non-asthmatic obese or eutrophic individuals.33 IL-8 stimulates inflammation by having a pro-inflammatory action and is related to the extent of neutrophilic inflammation due to chemotactic action for neutrophils.34 In addition, obesity alone can promote reduction of lung volumes such as FVC and expiratory reserve volume (EVR)10,35 due to the increase of adipose tissue in the abdominal and thoracic regions causing a restrictive disorder.

Finally, establishing a relationship between the inflammatory aspects of the individual with obesity and their pulmonary function is of great importance in clinical practice in the identification of the symptomatic cause and establishment of effective treatment, such as managing the asthma treatment in the obese in order to improve the profile especially related to interleukin-6 and weight loss as suggested recently.9

It was concluded that the lack of control of asthma symptoms, use of relief medication and interference in daily activities was related to worse lung function, in addition to the increase in pulmonary interleukin-6 being associated with worse lung function even in patients with controlled asthma, especially in the translate airway permeability measures. However, the lack of a control group and the cross-sectional design of this study limit the results extrapolation.