Macrophage activation, age and sex effects of immunometabolism in obese asthma

Periyalil, Hashim A.; Wood, Lisa G.; Scott, Hayley A.; Jensen, Megan E.; Gibson, Peter G.

doi:10.1183/09031936.00080514

Cited by 42 publications

(26 citation statements)

References 39 publications

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“…COPD phenotypes and pathogenesis demonstrate sex variation[93, 94]; additionally, biomarker levels and activity may vary between males and females. ET-1 demonstrates sex differences in the cardiovascular system[95] and kidney[96] and sCD163 has been found to be higher in women[97, 98], with possible modulation by sex hormones[99]. These associations require confirmation in a cohort including female participants.…”

Section: Discussionmentioning

confidence: 99%

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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Objective Chronic obstructive pulmonary disease (COPD) is a common co-morbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other co-morbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. Design Longitudinal observational study Methods 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, TNF-α), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. Results In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse FEV1 percent-predicted, and higher sCD163 associated with worse FEV1/FVC. IL-6, TNF-α, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. Conclusions Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment, and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of COPD in HIV-infected persons.

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Section: Discussionmentioning

confidence: 99%

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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“…Although several studies have linked leptin, a pro-inflammatory adipokine, and its related cytokines IL-6 and TNF, with asthma burden in obese individuals, these inflammatory markers are not routinely used in clinical care. Studies have reported elevated CRP among obese asthmatics [43], which correlates with lower pulmonary function [41] and airway hyper-responsiveness [44]. CRP decreases with weight loss and is associated with improved asthma control and quality of life [45].…”

Section: Discussionmentioning

confidence: 99%

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults

Rastogi

Jung

Strizich

et al. 2017

Respiratory Medicine

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Rationale Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. Objective To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. Methods Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n=1,126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. Results Of the 1,126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (β −138ml (95%CI −27ml, −249ml)) and FEV1 (β −155ml (95% CI −38ml, −272ml). Low HDL was also associated with lower FVC (β −111ml (−22ml, −201ml) and FEV1 (β −100ml (−12ml, −188ml)). Results were similar in men and women. Conclusions Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

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“…43 Obesity is known to be associated with inflammatory phenotypes which vary developmentally and with gender. 44 Recently, the novel hypothesis that the airway may be the target of systemic inflammation has been proposed. 45 In a study of two adult cohorts comprising more than 600 patients, asthma outcomes were related to serum IL-6 (a marker of systemic inflammation).…”

Section: Obesitymentioning

confidence: 99%

Severe asthma in children

2017

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Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed. First, the diagnosis of asthma should be confirmed, then co-morbidities assessed. Next, a nurse-led assessment further characterizes the problem, conventionally categorizing the child as either having difficult asthma or severe therapy-resistant asthma. Here, we reassess in particular the interactions between, and management of, these two categories, highlighting that this dichotomous classification may need reconsideration. We use bronchoscopy and an intramuscular steroid injection to determine if the child has steroid-resistant asthma, using a novel, multidomain approach because the adult definition does not apply to around half the children we see. Finally, we highlight some mechanistic data which have emerged from this protocol such as the absence of T-helper 2 (TH2) cytokines even in eosinophilic severe asthma and the potential role of the innate epithelial cytokine IL-33, novel data on lineage negative innate lymphoid cells, which we can measure in induced sputum, and demonstrating that intraepithelial neutrophils are associated with better, not worse asthma outcomes. Severe paediatric asthma is very different from severe asthma in adults, and approaches must not be uncritically extrapolated from adult disease to children.

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Macrophage activation, age and sex effects of immunometabolism in obese asthma

Cited by 42 publications

References 39 publications

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults

Severe asthma in children

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