Asthma and obesity are two epidemics affecting the developed world. The relationship between obesity and both asthma and severe asthma appears to be weight-dependent, causal, partly genetic, and ...probably bidirectional. There are two distinct phenotypes: 1. Allergic asthma in children with obesity, which worsens a pre-existing asthma, and 2. An often non allergic, late-onset asthma developing as a consequence of obesity. In obesity, infiltration of adipose tissue by macrophages M1, together with an increased expression of multiple mediators that amplify and propagate inflammation, is considered as the culprit of obesity-related inflammation. Adipose tissue is an important source of adipokines, such as pro-inflammatory leptin, produced in excess in obesity, and adiponectin with anti-inflammatory effects with reduced synthesis. The inflammatory process also involves the synthesis of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and TGFβ, which also contribute to asthma pathogenesis. In contrast, asthma pro-inflammatory cytokines such as IL-4, IL-5, IL-13, and IL-33 contribute to maintain the lean state. The resulting regulatory effects of the immunomodulatory pathways underlying both diseases have been hypothesized to be one of the mechanisms by which obesity increases asthma risk and severity. Reduction of weight by diet, exercise, or bariatric surgery reduces inflammatory activity and improves asthma and lung function.
Obese Asthma Syndrome: Much Work to Do Arismendi, Ebymar; Bantulà, Marina; Picado, César
Archivos de Bronconeumología,
August 2023, 2023-08-00, 20230801, Letnik:
59, Številka:
8
Journal Article
Obesity increases the risk of developing asthma in children and adults. Obesity is associated with different effects on lung function in children and adults. In adults, obesity has been associated ...with reduced lung function resulting from a relatively small effect on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), with the FEV1/FVC ratio remaining unchanged or mildly increased (restrictive pattern). In contrast, in children, obesity is associated with normal or higher FEV1 and FVC but a lower FEV1/FVC ratio (obstructive pattern). This anomaly has recently been associated with a phenomenon known as dysanapsis which results from a disproportionate growth between lung parenchyma size and airway calibre. The mechanisms that promote disproportionate lung parenchyma growth compared with airways in obese children remain to be elucidated. Obesity and dysanapsis in asthma patients might contribute to asthma morbidity by increasing airway obstruction, airway hyper-reactivity and airway inflammation. Obesity and dysanapsis in asthma patients are associated with increased medication use, more emergency department visits, hospitalizations and systemic corticosteroid burst than patients with normal weight. Dysanapsis may explain the reduced response to asthma medications in obese children. Weight loss results in a significant improvement in lung function, airway reactivity and asthma control. Whether these improvements are associated with the changes in the dysanaptic alteration is as yet unclear.
Obesity and asthma are associated with systemic inflammation maintained by mediators released by adipose tissue and lung. This study investigated the inflammatory serum mediator profile in obese ...subjects (O) (n = 35), non-obese asthma (NOA) patients (n = 14), obese asthmatics (OA) (n = 21) and healthy controls (HC) (n = 33). The effect of weight loss after bariatric surgery (BS) was examined in 10 OA and 31 O subjects. We analyzed serum markers including leptin, adiponectin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, ST2, IL-5, IL-9, and IL-18. Compared with HC subjects, the O group showed increased levels of leptin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, and ST2; the OA group presented increased levels of MCP-1, ezrin, YKL-40, and IL-18, and the NOA group had increased levels of ezrin, YKL-40, IL-5, and IL-18. The higher adiponectin/leptin ratio in NOA with respect to OA subjects was the only significant difference between the two groups. IL-9 was the only cytokine with significantly higher levels in OA with respect to O subjects. TNFR2, ezrin, MCP-1, and IL-18 concentrations significantly decreased in O subjects after BS. O, OA, and NOA showed distinct patterns of systemic inflammation. Leptin and adiponectin are regulated in asthma by obesity-dependent and -independent mechanisms. Combination of asthma and obesity does not result in significant additive effects on circulating cytokine levels.
The Platelet-Activating Factor (PAF)/receptor (PAFR) system is involved in asthma and allergic rhinitis; however, its role in chronic rhinosinusitis (CRS) is still unclear. This study aimed to assess ...the expression of PAFR and the concentration of Lyso-PAF isoforms in the nasal polyps (NP) of patients suffering from CRS with/without comorbidities such as asthma and NSAID-exacerbated respiratory disease (N-ERD) compared to healthy nasal mucosa (NM) from control subjects.
NM (
= 8) and NP tissues were obtained from patients undergoing surgery for septal deviation/turbinate hypertrophy or endoscopic sinus surgery, respectively. Three phenotypes were studied: CRSwNP with no asthma (
= 6), CRSwNP with non-steroidal anti-inflammatory drug (NSAID)-tolerant asthma (
= 6), and CRSwNP with NSAID-exacerbated respiratory disease (
= 6). PAFR protein and mRNA were assessed via immunochemistry, immunofluorescence, Western blot, and real-time quantitative PCR. Lyso-PAF isoforms (C16, C18, and C18:1) were quantified via mass spectrometry.
PAFR protein was expressed in the NM and NP, concretely in epithelial cells and submucosal glands. Compared to NM, PAFR mRNA expression was higher in all NP phenotypes (
< 0.05) while all Lyso-PAF isoform concentrations were higher in the NP from asthmatic patients (
< 0.05). Lyso-PAF C16 and C18 concentrations were higher in the NP from asthmatic patients than in the NP from patients without asthma.
The PAF/PAFR system could play a pathophysiological role in CRSwNP pathogenesis.
Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The ...aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (
,
,
,
, and
) and underexpressed genes (
,
,
, and
) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of
and
and had no effects on
,
, and
. In underexpressed genes, obesity did not affect
,
, and
and significantly reduced
expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.
Obesity is known to impair the efficacy of glucocorticoid medications for asthma control. Glucocorticoid-induced gene expression studies may be useful to discriminate those obese asthmatic patients ...who present a poor response to glucocorticoids. The expression of genes of interest is normalized with respect to reference genes (RGs). Ideally, RGs have a stable expression in different samples and are not affected by experimental conditions. The objective of this work was to analyze suitable RGs to study the role of glucocorticoid-induced genes in obese asthmatic patients in further research. The gene expression of eight potential RGs (
,
,
,
,
,
,
, and
) was assessed with reverse transcription-quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from asthmatic, obese asthmatic, and healthy individuals. Their stability was analyzed using four different algorithms-BestKeeper, ΔCt, geNorm, and NormFinder. geNorm analysis recommended the use of a minimum of three genes for normalization. Moreover, intergroup variation due to the treatment was calculated by NormFinder, which found that
was the gene that was least affected by different treatments. Comprehensive rankings indicated
and
as the best RGs for qPCR in PBMCs from healthy and asthmatic subjects, while
and
were the best for obese asthmatic subjects. Finally, our results demonstrated that
and
were the most stable RGs among all groups, whereas
,
, and
were the worst shared ones.
Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to ...inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss.
The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 51-59 years), 14 nonobese asthma patients (NOA) (11 females; 53 43-60 years), 15 obese patients (OP) (13 females; 47 45-60 years), and 19 healthy controls (HC) (14 females; 43 34-56 years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2.
We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA.
The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.
The obese asthma syndrome (OAS) is characterized by increased airway inflammation and impaired lung function. Obesity-induced inflammation, characterized by elevated pro-inflammatory cytokines and ...reduced anti-inflammatory adipokines, contributes to airway inflammation and asthma symptoms. Asthmatic patients with obesity often have a poor response to inhaled corticosteroids (ICS), which are the mainstay of asthma treatment. They achieve less asthma control, more hospitalizations, and experience a poorer quality of life. The detrimental effects of obesity on lung function and the additive or synergistic effects of systemic inflammation contribute to this reduced response to glucocorticoids. Additionally, studies have suggested a potential association between vitamin D deficiency, obesity, and asthma exacerbations. Low vitamin D levels have also been linked to glucocorticoid resistance, while in vitro evidence suggests that vitamin D can enhance the effectiveness of glucocorticoids. Weight loss through bariatric surgery shows promising results in improving asthma control and reducing airway inflammation.
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