BMI but not central obesity predisposes to airway closure during bronchoconstriction
Corresponding Author
Ubong Peters
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Correspondence: Ubong Peters, Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, HSRF D230, 149 Beaumont Avenue, Burlington, VT 05405, USA. Email: [email protected]Search for more papers by this authorMeenakumari Subramanian
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorDavid G. Chapman
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Translational Airways Group, University of Technology, Sydney, NSW, Australia
Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, Sydney, NSW, Australia
Search for more papers by this authorDavid A. Kaminsky
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorCharles G. Irvin
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorRobert A. Wise
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorGwen S. Skloot
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Search for more papers by this authorJason H.T. Bates
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorAnne E. Dixon
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorCorresponding Author
Ubong Peters
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Correspondence: Ubong Peters, Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, HSRF D230, 149 Beaumont Avenue, Burlington, VT 05405, USA. Email: [email protected]Search for more papers by this authorMeenakumari Subramanian
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorDavid G. Chapman
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Translational Airways Group, University of Technology, Sydney, NSW, Australia
Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, Sydney, NSW, Australia
Search for more papers by this authorDavid A. Kaminsky
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorCharles G. Irvin
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorRobert A. Wise
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorGwen S. Skloot
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Search for more papers by this authorJason H.T. Bates
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorAnne E. Dixon
Division of Pulmonary and Critical Care Medicine, Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, VT, USA
Search for more papers by this authorABSTRACT
Background and objective
Obesity produces restrictive effects on lung function. We previously reported that obese patients with asthma exhibit a propensity towards small airway closure during methacholine challenge which improved with weight loss. We hypothesized that increased abdominal adiposity, a key contributor to the restrictive effects of obesity on the lung, mediates this response. This study investigates the effect of body mass index (BMI) versus waist circumference (WC) on spirometric lung function, sensitivity to airway narrowing and closure, and airway closure during bronchoconstriction in patients with asthma.
Methods
Participants underwent spirometry and methacholine challenge. Sensitivity to airway closure and narrowing was assessed from the dose–response slopes of the forced vital capacity (FVC) and the ratio of forced expiratory volume in 1 s (FEV1) to FVC, respectively. Airway closure during bronchoconstriction (closing index) was computed as the percent reduction in FVC divided by the percent reduction in FEV1 at maximal bronchoconstriction.
Results
A total of 116 asthmatic patients (56 obese) underwent methacholine challenge. Spirometric lung function was inversely related to WC (P < 0.05), rather than BMI. Closing index increased significantly during bronchoconstriction in obese patients and was related to increasing BMI (P = 0.01), but not to WC. Sensitivity to airway closure and narrowing was not associated with BMI or WC.
Conclusion
Although WC is associated with restrictive effects on baseline lung function, increased BMI, rather than WC, predisposes to airway closure during bronchoconstriction. These findings suggest that obesity predisposes to airway closure during bronchoconstriction through mechanisms other than simple mass loading.
Supporting Information
| Filename | Description |
|---|---|
| RESP13478-sup001-TableS1-S2.docWord document, 53 KB |
Table S1 Baseline demographics of study population by waist-to-hip ratio quartile. Table S2 Multivariate regression analysis of relationship between anthropomorphic measures and lung function. |
| RESP13478-sup002-VisualAbstract.pptxPowerPoint 2007 presentation , 233.4 KB | Visual Abstract Impact of general vs central obesity on baseline lung function and airway closure during bronchoconstriction. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am. J. Respir. Crit. Care Med. 2007; 175: 661–6.
- 2Schatz M, Hsu JW, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, Haselkorn T. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J. Allergy Clin. Immunol. 2014; 133: 1549–56.
- 3Mosen DM, Schatz M, Magid DJ, Camargo CA Jr. The relationship between obesity and asthma severity and control in adults. J. Allergy Clin. Immunol. 2008; 122: 507–11.e6.
- 4Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R, Castro M, Curran-Everett D, Fitzpatrick AM et al.; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am. J. Respir. Crit. Care Med. 2010; 181: 315–23.
- 5Sutherland ER, Goleva E, Strand M, Beuther DA, Leung DY. Body mass and glucocorticoid response in asthma. Am. J. Respir. Crit. Care Med. 2008; 178: 682–7.
- 6Dixon A. The treatment of asthma in obesity. Expert Rev. Respir. Med. 2012; 6: 331–40.
- 7Watson RA, Pride NB, Thomas EL, Fitzpatrick J, Durighel G, McCarthy J, Morin SX, Ind PW, Bell JD. Reduction of total lung capacity in obese men: comparison of total intrathoracic and gas volumes. J. Appl. Physiol. (1985) 2010; 108: 1605–12.
- 8Hedenstierna G, Santesson J. Breathing mechanics, dead space and gas exchange in the extremely obese, breathing spontaneously and during anaesthesia with intermittent positive pressure ventilation. Acta Anaesthesiol. Scand. 1976; 20: 248–54.
- 9Naimark A, Cherniack RM. Compliance of the respiratory system and its components in health and obesity. J. Appl. Physiol. 1960; 15: 377–82.
- 10Sharp JT, Henry JP, Sweany SK, Meadows WR, Pietras RJ. The total work of breathing in normal and obese men. J. Clin. Invest. 1964; 43: 728–39.
- 11Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest 2006; 130: 827–33.
- 12Chapman DG, Irvin CG, Kaminsky DA, Forgione PM, Bates JH, Dixon AE. Influence of distinct asthma phenotypes on lung function following weight loss in the obese. Respirology 2014; 19: 1170–7.
- 13Chapman DG, Berend N, King GG, Salome CM. Increased airway closure is a determinant of airway hyperresponsiveness. Eur. Respir. J. 2008; 32: 1563–9.
- 14Burgess JA, Matheson MC, Diao F, Johns DP, Erbas B, Lowe AJ, Gurrin LC, Lodge CJ, Thomas PS, Morrison S et al. Bronchial hyperresponsiveness and obesity in middle age: insights from an Australian cohort. Eur. Respir. J. 2017; 50: 1602181.
- 15Litonjua AA, Sparrow D, Celedon JC, DeMolles D, Weiss ST. Association of body mass index with the development of methacholine airway hyperresponsiveness in men: the Normative Aging Study. Thorax 2002; 57: 581–5.
- 16Wehrmeister FC, Menezes AM, Muniz LC, Martínez-Mesa J, Domingues MR, Horta BL. Waist circumference and pulmonary function: a systematic review and meta-analysis. Syst. Rev. 2012; 1: 55.
- 17Pouliot MC, Després JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, Nadeau A, Lupien PJ. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am. J. Cardiol. 1994; 73: 460–8.
- 18Leone N, Courbon D, Thomas F, Bean K, Jégo B, Leynaert B, Guize L, Zureik M. Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am. J. Respir. Crit. Care Med. 2009; 179: 509–16.
- 19Sorlí-Aguilar M, Martín-Luján F, Flores-Mateo G, Jardí-Piñana C, Aparicio-Llopis E, Basora-Gallisà J, Solà-Alberich R, ESPITAP Study Group Investigators. Adiposity markers and lung function in smokers: a cross-sectional study in a Mediterranean population. BMC Pulm. Med. 2016; 16: 178.
- 20Sideleva O, Suratt BT, Black KE, Tharp WG, Pratley RE, Forgione P, Dienz O, Irvin CG, Dixon AE. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am. J. Respir. Crit. Care Med. 2012; 186: 598–605.
- 21Barton JH, Ireland A, Fitzpatrick M, Kessinger C, Camp D, Weinman R, McMahon D, Leader JK, Holguin F, Wenzel SE et al. Adiposity influences airway wall thickness and the asthma phenotype of HIV-associated obstructive lung disease: a cross-sectional study. BMC Pulm. Med. 2016; 16: 111.
- 22Desai AG, Togias A, Schechter C, Fisher B, Parow A, Skloot G. Peripheral airways dysfunction in obesity reflects increased bronchomotor tone. J. Allergy Clin. Immunol. 2015; 135: 820–2.
- 23Oppenheimer BW, Berger KI, Ali S, Segal LN, Donnino R, Katz S, Parikh M, Goldring RM. Pulmonary vascular congestion: a mechanism for distal lung unit dysfunction in obesity. PLoS One 2016; 11: e0152769.
- 24Al-Alwan A, Bates JH, Chapman DG, Kaminsky DA, DeSarno MJ, Irvin CG, Dixon AE. The nonallergic asthma of obesity. A matter of distal lung compliance. Am. J. Respir. Crit. Care Med. 2014; 189: 1494–502.
- 25 American Lung Association–Asthma Clinical Research Centers' Writing Committee, Dixon AE, Castro M, Cohen RI, Gerald LB, Holbrook JT, Irvin CG, Mohapatra S, Peters SP, Rayapudi S et al. Efficacy of nasal mometasone for the treatment of chronic sinonasal disease in patients with inadequately controlled asthma. J. Allergy Clin. Immunol. 2015; 135: 701–9.e5.
- 26Dixon AE, Sugar EA, Zinreich SJ, Slavin RG, Corren J, Naclerio RM, Ishii M, Cohen RI, Brown ED, Wise RA et al.; American Lung Association-Asthma Clinical Research Centers. Criteria to screen for chronic sinonasal disease. Chest 2009; 136: 1324–32.
- 27Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, Kosinski M, Pendergraft TB, Jhingran P. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J. Allergy Clin. Immunol. 2006; 117: 549–56.
- 28Revicki DA, Leidy NK, Brennan-Diemer F, Sorensen S, Togias A. Integrating patient preferences into health outcomes assessment: the multiattribute Asthma Symptom Utility Index. Chest 1998; 114: 998–1007.
- 29Valsamakis G, Chetty R, Anwar A, Banerjee AK, Barnett A, Kumar S. Association of simple anthropometric measures of obesity with visceral fat and the metabolic syndrome in male Caucasian and Indo-Asian subjects. Diabet. Med. 2004; 21: 1339–45.
- 30Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome – a new worldwide definition. Lancet 2005; 366: 1059–62.
- 31Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am. J. Respir. Crit. Care Med. 2000; 161: 309–29.
- 32Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P et al.; ATS/ERS Task Force. Standardisation of spirometry. Eur. Respir. J. 2005; 26: 319–38.
- 33Peat JK, Salome CM, Berry G, Woolcock AJ. Relation of dose-response slope to respiratory symptoms and lung function in a population study of adults living in Busselton, Western Australia. Am. Rev. Respir. Dis. 1992; 146: 860–5.
- 34O'Connor G, Sparrow D, Taylor D, Segal M, Weiss S. Analysis of dose-response curves to methacholine. An approach suitable for population studies. Am. Rev. Respir. Dis. 1987; 136: 1412–7.
- 35Peters U, Suratt BT, Bates JHT, Dixon AE. Beyond BMI: obesity and lung disease. Chest 2018; 153: 702–9.
- 36Forno E, Weiner DJ, Mullen J, Sawicki G, Kurland G, Han YY, Cloutier MM, Canino G, Weiss ST, Litonjua AA et al. Obesity and airway dysanapsis in children with and without asthma. Am. J. Respir. Crit. Care Med. 2017; 195: 314–23.
- 37Bande J, Clément J, Van de Woestijne KP. The influence of smoking habits and body weight on vital capacity and FEV1 in male Air Force personnel: a longitudinal and cross-sectional analysis. Am. Rev. Respir. Dis. 1980; 122: 781–90.
- 38Skloot G, Schechter C, Desai A, Togias A. Impaired response to deep inspiration in obesity. J. Appl. Physiol. 2011; 111: 726–34.
- 39De Blasio MJ, Boije M, Kempster SL, Smith GC, Charnock-Jones DS, Denyer A, Hughes A, Wooding FB, Blache D, Fowden AL et al. Leptin matures aspects of lung structure and function in the ovine fetus. Endocrinology 2016; 157: 395–404.
- 40Schachter LM, Salome CM, Peat JK, Woolcock AJ. Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness. Thorax 2001; 56: 4–8.
- 41Sood A, Verhulst SJ, Varma A, Eagleton LE, Henkle JQ, Hopkins-Price P. Association of excess weight and degree of airway responsiveness in asthmatics and non-asthmatics. J. Asthma 2006; 43: 447–52.
- 42Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M et al. Effect of distinct lifestyle interventions on mobilization of fat storage pools: the CENTRAL MRI randomized controlled trial. Circulation 2018; 137: 1143–57.
- 43Tinggaard J, Hagen CP, Christensen AN, Mouritsen A, Mieritz MG, Wohlfahrt-Veje C, Helge JW, Beck TN, Fallentin E, Larsen R et al. Anthropometry, DXA, and leptin reflect subcutaneous but not visceral abdominal adipose tissue on MRI in 197 healthy adolescents. Pediatr. Res. 2017; 82: 620–8.
- 44Torday JS, Powell FL, Farmer CG, Orgeig S, Nielsen HC, Hall AJ. Leptin integrates vertebrate evolution: from oxygen to the blood-gas barrier. Respir. Physiol. Neurobiol. 2010; 173(Suppl.): S37–42.
- 45Arteaga-Solis E, Zee T, Emala CW, Vinson C, Wess J, Karsenty G. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab. 2013; 17: 35–48.
