Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

Abstract

Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesityinduced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

Risk factors for chronic lung disease and asthma differ among children born extremely preterm

“…Our findings are consistent with a meta‐analysis of 31 European cohort studies that identified that a higher infant weight gain in premature infants was associated with preschool wheezing and childhood asthma . Obesity during puberty has been linked to increased growth velocity in the first years of life and obesity is associated with childhood asthma . A proposed mechanism for this association is the release of immunomodulatory cytokines from adipose tissue leading to airway hyper‐responsiveness or through mechanical restriction of the chest wall; however, the association between asthma and obesity is often confounded by deconditioning …”

“…36 Obesity during puberty has been linked to increased growth velocity in the first years of life 37 and obesity is associated with childhood asthma. [38][39][40] A proposed mechanism for this association is the release of immunomodulatory cytokines from adipose tissue leading to airway hyper-responsiveness or through mechanical restriction of the chest wall; however, the association between asthma and obesity is often confounded by deconditioning. 39 We found that tracheal colonization in the neonatal period was associated with a decreased risk of asthma.…”

“…[38][39][40] A proposed mechanism for this association is the release of immunomodulatory cytokines from adipose tissue leading to airway hyper-responsiveness or through mechanical restriction of the chest wall; however, the association between asthma and obesity is often confounded by deconditioning. 39 We found that tracheal colonization in the neonatal period was associated with a decreased risk of asthma. The relationship between lung and gut microbiota and childhood asthma appears to be complex.…”

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

“…49 Atopic asthma is characterized by high eosinophil, mast cell, and T-lymphocyte counts, whereas nonatopic asthma displays high neutrophil and mast cell counts. 49 Muc et al 50 reported that the main change in obese asthmatic patients was the shift of immune response from T H 2 (a typical atopic immunologic profile) to T H 1. Thus the type of airway inflammation driven mainly by neutrophils 51 in obese subjects might partially explain the stronger relationship of obesity with later-onset and nonatopic asthma.…”

Animal models of obesity and diabetes mellitus

“…Comorbidities directly associated with excess body fat include T2DM, certain cancers and cardiovascular diseases including hypertension, coronary artery disease and stroke 9 . More severe cases of obesity are associated with an increased incidence of sleep apnea 10,11 , asthma [12][13][14] , gallstones 15 , steatohepatitis 16 , glomerulosclerosis 17 , dyslipidaemia and endothelial dysfunction 18,19 . The metabolic complications linked to obesity are often attributed to systemic processes such as metabolic inflammation or cellular pathologies such as mitochondrial dysfunction 20 and/or stress of the endoplasmic reticulum due to lipotoxicity 19,21 .…”