Adiposity influences airway wall thickness and the asthma phenotype of HIV-associated obstructive lung disease: a cross-sectional study

Barton et al. BMC Pulmonary Medicine (2016) 16:111 DOI 10.1186/s12890-016-0274-5 RESEARCH ARTICLE Open Access Adiposity influences airway wall thickness and the asthma phenotype of HIVassociated obstructive lung disease: a cross-sectional study Julia H. Barton1, Alex Ireland1, Meghan Fitzpatrick1, Cathy Kessinger1, Danielle Camp1, Renee Weinman1, Deborah McMahon1, Joseph K. Leader1, Fernando Holguin1,3, Sally E. Wenzel1, Alison Morris1,2 and Matthew R. Gingo1,4* Abstract Background: Airflow obstruction, which encompasses several phenotypes, is common among HIV-infected individuals. Obesity and adipose-related inflammation are associated with both COPD (fixed airflow obstruction) and asthma (reversible airflow obstruction) in HIV-uninfected persons, but the relationship to airway inflammation and airflow obstruction in HIV-infected persons is unknown. The objective of this study was to determine if adiposity and adipose-associated inflammation are associated with airway obstruction phenotypes in HIV-infected persons. Methods: We performed a cross-sectional analysis of 121 HIV-infected individuals assessed with pulmonary function testing, chest CT scans for measures of airway wall thickness (wall area percent [WA%]) and adipose tissue volumes (mediastinal and subcutaneous), as well as HIV- and adipose-related inflammatory markers. Participants were defined as COPD phenotype (post-bronchodilator FEV1/FVC < lower limit of normal) or asthma phenotype (doctordiagnosed asthma or bronchodilator response). Pearson correlation coefficients were calculated between adipose measurements, WA%, and pulmonary function. Multivariable logistic and linear regression models were used to determine associations of airflow obstruction and airway remodeling (WA%) with adipose measurements and participant characteristics. Results: Twenty-three (19 %) participants were classified as the COPD phenotype and 33 (27 %) were classified as the asthma phenotype. Body mass index (BMI) was similar between those with and without COPD, but higher in those with asthma compared to those without (mean [SD] 30.7 kg/m2 [8.1] vs. 26.5 kg/m2 [5.3], p = 0.008). WA% correlated with greater BMI (r = 0.55, p < 0.001) and volume of adipose tissue (subcutaneous, r = 0.40; p < 0.001; mediastinal, r = 0.25; p = 0.005). Multivariable regression found the COPD phenotype associated with greater age and pack-years smoking; the asthma phenotype with younger age, female gender, smoking history, and lower adiponectin levels; and greater WA% with greater BMI, younger age, higher soluble CD163, and higher CD4 counts. Conclusions: Adiposity and adipose-related inflammation are associated with an asthma phenotype, but not a COPD phenotype, of obstructive lung disease in HIV-infected persons. Airway wall thickness is associated with adiposity and inflammation. Adipose-related inflammation may play a role in HIV-associated asthma. Keywords: HIV, Asthma, COPD, Obstructive lung disease, Obesity, Lipodystrophy, Adiponectin * Correspondence: 1 Department of Medicine, University of Pittsburgh, Pittsburgh, USA 4 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, 3459 Fifth Avenue, 628 NW, Pittsburgh, PA 15213, USA Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Barton et al. BMC Pulmonary Medicine (2016) 16:111 Background Obstructive lung disease, encompassing many phenotypes of both fixed and reversible airflow obstruction, is common in HIV-infected persons [1–6]. Chronic obstructive pulmonary disease (COPD) in the HIV-infected population is accelerated in smokers and those with poor control of the viral load [1, 3, 7, 8]. Asthma is another commonly diagnosed chronic pulmonary disease in HIV-infected persons [9, 10]. Despite the prevalence of COPD and asthma in HIV-infected persons, little is known about their pathogenesis in this population. Obesity influences the development of both COPD and asthma in the HIV-uninfected population. Obesity is more prevalent in individuals with mild COPD compared to the general population, however, the causal nature of the relationship between obesity and COPD is unclear [11, 12]. Obesity, central adiposity, and aspects of the metabolic syndrome have been implicated in the pathogenesis of the adult-onset phenotype of asthma [13–17]. Inflammation related to visceral adipose tissue is thought to drive this association [18]. We have previously shown that doctor-diagnosed asthma in HIV is frequently adult-onset, associated with inflammatory markers common in chronic HIV infection, and 2.5 times more likely in obese compared to normal weight HIV-infected persons [9]. Metabolic effects of HIV and highly-active antiretroviral therapy (HAART) that lead to central adiposity and alterations in inflammation may be relevant to the pathogenesis of airway obstruction in HIV [19, 20]. Long-term HIV infection is associated with chronic inflammation and macrophage activation, measured by high-sensitivity Creactive protein (CRP) and soluble CD163 (sCD163), respectively [21–26]. Increased central adiposity is associated with the alteration of systemic adipokine profiles, including higher leptin (a pro-inflammatory cytokine) and lower adiponectin (an anti-inflammatory cytokine). Adiponectin is lower in HIV-infected persons and in chronic inflammation [27]; and reduced levels of adiponectin have been implicated in several HIV-associated co-morbidities such as cardiovascular disease and neurocognitive dysfunction [28–30]. In the HIV-uninfected population, levels of adiponectin are lower in asthma and paradoxically higher in COPD [31]. The relationship of adiponectin in HIV-associated obstructive lung disease is unknown. Obstructive lung disease can manifest subjectively as pulmonary symptoms or objectively as pulmonary function changes or airway remodeling detectable on computed tomography (CT) scan [32–34]. Asthma is often diagnosed by doctors based on episodic, recurrent pulmonary symptoms, such as wheezing. Pulmonary symptoms are more common in HIV-infected individuals with doctor-diagnosed asthma than those without asthma [9]. Airway wall thickening correlates with asthma severity, Page 2 of 10 airflow obstruction, and histopathological changes related to asthma [35–37]. Airway remodeling quantitatively measured by CT scan has not (...truncated)