Exertional Dyspnea in Childhood: Is There an Iceberg Beneath the Apex?

in Pediatric Exercise Science

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Paolo T. PianosiUniversity of Minnesota

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This essay expounds on fundamental, quantitative elements of the exercise ventilation in children, which was the subject of the Tom Rowland Lecture given at the NASPEM 2018 Conference. Our knowledge about how much ventilation rises during aerobic exercise is reasonably solid; our understanding of its governance is a work in progress, but our grasp of dyspnea and ventilatory limitation in children (if it occurs) remains embryonic. This manuscript summarizes ventilatory mechanics during dynamic exercise, then proceeds to outline our current understanding of mechanisms of dyspnea, particularly during exercise (exertional dyspnea). Most research in this field has been done in adults, and the vast majority of these studies in patients with chronic obstructive pulmonary disease. To what extent conclusions drawn from this literature apply to children and adolescents—both healthy and those with cardiopulmonary disease—will be discussed. The few, recent, pertinent, pediatric studies will be reviewed in an attempt to provide an empirical basis for proposing a hypothetical model to study exertional dyspnea in youth. Just as somatic growth will have consequences for ventilatory and exercise capacity, so too will neural developmental plasticity and experience affect perception of dyspnea. Our path to understand how these evolving inputs and influences summate during a child’s life will be Columbus’ India.

Pianosi is with the Division of Pediatric Pulmonology & Sleep Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, MN.

Pianosi (ppianosi@umn.edu) is corresponding author.
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  • 1.

    Babb TG. Exercise ventilatory limitation: the role of expiratory flow limitation. Exerc Sport Sci Rev. 2013;41(1):118. PubMed ID: 23038244 doi:10.1097/JES.0b013e318267c0d2

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Banzett RB, Dempsey JA, O’Donnell DE, Wamboldt MZ. Symptom perception and respiratory sensation in asthma. Am J Respir Crit Care Med. 2000;162(3, pt 1):117882. PubMed ID: 10988151 doi:10.1164/ajrccm.162.3.9909112

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Bellofiore S, Ricciardolo FL, Ciancio N, et al. Changes in respiratory drive account for the magnitude of dyspnoea during bronchoconstriction in asthmatics. Eur Respir J. 1996;9(6):11559. PubMed ID: 8804931 doi:10.1183/09031936.96.09061155

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Binks AP, Moosavi SH, Banzett RB, Schwartzstein RM. “Tightness” sensation of asthma does not arise from the work of breathing. Am J Respir Crit Care Med. 2002;165(1):7882. PubMed ID: 11779734 doi:10.1164/ajrccm.165.1.2105061

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Bokov P, Fiamma MN, Chevalier-Bidaud B, et al. Increased ventilatory variability and complexity in patients with hyperventilation disorder. J Appl Physiol. 2016;120(10):116572. doi:10.1152/japplphysiol.00859.2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Borel B, Leclair E, Thevenet D, Beghin L, Gottrand F, Fabre C. Mechanical ventilatory constraints during incremental exercise in healthy and cystic fibrosis children. Pediatr Pulmonol. 2014;49(3):2219. PubMed ID: 23765600 doi:10.1002/ppul.22804

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Burdon JG, Juniper EF, Killian KJ, Hargreave FE, Campbell EJ. The perception of breathlessness in asthma. Am Rev Respir Dis. 1982;126(5):8258. PubMed ID: 7149447

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Casaburi R, Rennard SI. Exercise limitation in chronic obstructive pulmonary disease. The O’Donnell threshold. Am J Respir Crit Care Med. 2015;191(8):8735. PubMed ID: 25876202 doi:10.1164/rccm.201501-0084ED

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Cooper DM, Kaplan MR, Baumgarten L, Weiler-Ravell D, Whipp BJ, Wasserman K. Coupling of ventilation and CO2 production during exercise in children. Pediatr Res 1987;21(6):56872. PubMed ID: 3110725 doi:10.1203/00006450-198706000-00012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    De Baets F, Bodart E, Dramaix-Wilmet M, et al. Exercise-induced respiratory symptoms are poor predictors of bronchoconstriction. Pediatr Pulmonol. 2005;39(4):3015. PubMed ID: 15678500 doi:10.1002/ppul.20185

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    De Peuter S, Van Diest I, Lemaigre V, Verleden G, Demedts M, Van den Bergh O. Dyspnea: the role of psychological processes. Clin Psychol Rev. 2004;24(5):55781. PubMed ID: 15325745 doi:10.1016/j.cpr.2004.05.001

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Dodd JD, Barry SC, Gallagher CG. Respiratory factors do not limit maximal symptom-limited exercise in patients with mild cystic fibrosis lung disease. Respir Physiol Neurobiol. 2006;152(2):17685. PubMed ID: 16169290 doi:10.1016/j.resp.2005.08.003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Dominelli PB, Archiza B, Ramsook AH, et al. Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise. Exp Physiol. 2017;102(11):153547. PubMed ID: 28841267 doi:10.1113/EP086566

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120(11):376072. PubMed ID: 21041958 doi:10.1172/JCI42843

  • 15.

    Emerson SR, Kurti SP, Rosenkranz SK, Smith JR, Harms CA. Decreased prevalence of exercise expiratory flow limitation from pre- to postpuberty. Med Sci Sports Exerc. 2015;47(7):150311. PubMed ID: 25380473 doi:10.1249/MSS.0000000000000566

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Feldman JM, Steinberg D, Kutner H, et al. Perception of pulmonary function and asthma control: the differential role of child versus caregiver anxiety and depression. J Pediatr Psychol. 2013;38(10):1091100. PubMed ID: 23873703 doi:10.1093/jpepsy/jst052

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Forster HV, Haouzi P, Dempsey JA. Control of breathing during exercise. Compr Physiol. 2012;2(1):74377. PubMed ID: 23728984

  • 18.

    Godfrey S. Exercise Testing in Children. London: WB Saunders; 1974.

  • 19.

    Guenette JA, Webb KA, O’Donnell DE. Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD? Eur Respir J. 2012;40(2):3229. PubMed ID: 22183485 doi:10.1183/09031936.00157711

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Herigstad M, Hayen A, Wiech K, Pattinson KT. Dyspnoea and the brain. Respir Med. 2011;105(6):80917. PubMed ID: 21295457 doi:10.1016/j.rmed.2010.12.022

  • 21.

    Ingle L, Cleland JG, Clark AL. Body mass index is related to the perception of exertional breathlessness in patients presenting with dyspnoea of unknown origin. Int J Cardiol. 2012;157(2):3003. PubMed ID: 22483253 doi:10.1016/j.ijcard.2012.03.113

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Johansson H, Norlander K, Berglund L, et al. Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population. Thorax .2015;70(1):5763. PubMed ID: 25380758 doi:10.1136/thoraxjnl-2014-205738

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Johansson H, Norlander K, Hedenstrom H, et al. Exercise-induced dyspnea is a problem among the general adolescent population. Respir Med. 2014;108(6):8528. PubMed ID: 24731799 doi:10.1016/j.rmed.2014.03.010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am Rev Respir Dis. 1991;143(5 Pt 1):96877. PubMed ID: 2024852 doi:10.1164/ajrccm/143.5_Pt_1.968

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol (1985). 1992;73(3):87486. doi:10.1152/jappl.1992.73.3.874

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Julius SM, Davenport KL, Davenport PW. Perception of intrinsic and extrinsic respiratory loads in children with life-threatening asthma. Pediatr Pulmonol. 2002;34(6):42533. PubMed ID: 12422340 doi:10.1002/ppul.10199

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Kamal AH, Maguire JM, Wheeler JL, Currow DC, Abernethy AP. Dyspnea review for the palliative care professional: treatment goals and therapeutic options. J Palliat Med. 2012;15(1):10614. PubMed ID: 22268406 doi:10.1089/jpm.2011.0110

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Lamprecht B, Vanfleteren LE, Studnicka M, et al. Sex-related differences in respiratory symptoms: results from the BOLD Study. Eur Respir J. 2013;42(3):85860. PubMed ID: 24000253 doi:10.1183/09031936.00047613

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Laveneziana P, Webb KA, Ora J, Wadell K, O’Donnell DE. Evolution of dyspnea during exercise in chronic obstructive pulmonary disease: impact of critical volume constraints. Am J Respir Crit Care Med. 2011;184(12):136773. PubMed ID: 21885624 doi:10.1164/rccm.201106-1128OC

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Lougheed MD, Fisher T, O’Donnell DE. Dynamic hyperinflation during bronchoconstriction in asthma: implications for symptom perception. Chest .2006;130(4):107281. PubMed ID: 17035440 doi:10.1378/chest.130.4.1072

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Lougheed MD, Lam M, Forkert L, Webb KA, O’Donnell DE. Breathlessness during acute bronchoconstriction in asthma. Pathophysiologic mechanisms. Am Rev Respir Dis. 1993;148(6, pt 1):14529. PubMed ID: 8256884 doi:10.1164/ajrccm/148.6_Pt_1.1452

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Lovering AT, Elliott JE, Laurie SS, et al. Ventilatory and sensory responses in adult survivors of preterm birth and bronchopulmonary dysplasia with reduced exercise capacity. Ann Am Thorac Soc. 2014;11(10):152837. PubMed ID: 25380058 doi:10.1513/AnnalsATS.201312-466OC

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Mahler DA, O’Donnell DE. Recent advances in dyspnea. Chest. 2015;147(1):23241. PubMed ID: 25560861 doi:10.1378/chest.14-0800

  • 34.

    McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol. 1998;84(6):187281. doi:10.1152/jappl.1998.84.6.1872

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    McClaran SR, Wetter TJ, Pegelow DF, Dempsey JA. Role of expiratory flow limitation in determining lung volumes and ventilation during exercise. J Appl Physiol. 1999;86(4):135766. doi:10.1152/jappl.1999.86.4.1357

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Mead J. Control of respiratory frequency. Journal of Applied Physiology. 1960;15(3):32536. doi:10.1152/jappl.1960.15.3.325

  • 37.

    Mead J. Functional significance of the area of apposition of diaphragm to rib cage [proceedings]. Am Rev Respir Dis. 1979;119(2 Pt 2):312. PubMed ID: 426349

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Milic-Emili G, Petit JM, Deroanne R. Mechanical work of breathing during exercise in trained and untrained subjects. J Appl Physiol. 1962;17:436. PubMed ID: 14473890 doi:10.1152/jappl.1962.17.1.43

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Molgat-Seon Y, Dominelli PB, Ramsook AH, et al. The effects of age and sex on mechanical ventilatory constraint and dyspnea during exercise in healthy humans. J Appl Physiol (1985). 2018;124(4):1092106. doi:10.1152/japplphysiol.00608.2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Moorcroft AJ, Dodd ME, Morris J, Webb AK. Symptoms, lactate and exercise limitation at peak cycle ergometry in adults with cystic fibrosis. Eur Respir J. 2005;25(6):10506. PubMed ID: 15929961 doi:10.1183/09031936.05.00011404

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Moy ML, Lantin ML, Harver A, Schwartzstein RM. Language of dyspnea in assessment of patients with acute asthma treated with nebulized albuterol. Am J Respir Crit Care Med. 1998;158(3):74953. PubMed ID: 9731000 doi:10.1164/ajrccm.158.3.9707088

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Moy ML, Woodrow Weiss J, Sparrow D, Israel E, Schwartzstein RM. Quality of dyspnea in bronchoconstriction differs from external resistive loads. Am J Respir Crit Care Med. 2000;162(2, pt 1):4515. PubMed ID: 10934069 doi:10.1164/ajrccm.162.2.9907138

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Nourry C, Deruelle F, Fabre C, et al. Evidence of ventilatory constraints in healthy exercising prepubescent children. Pediatr Pulmonol. 2006;41(2):13340. PubMed ID: 16358342 doi:10.1002/ppul.20332

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Nourry C, Deruelle F, Fabre C, et al. Exercise flow-volume loops in prepubescent aerobically trained children. J Appl Physiol. 2005;99(5):191221. doi:10.1152/japplphysiol.00323.2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Nuijsink M, Hop WC, Jongste JC, Sterk PJ, Duiverman AE, Cato Study G. Perception of bronchoconstriction: a complementary disease marker in children with asthma. J Asthma. 2013;50(6):5604. PubMed ID: 23672570 doi:10.3109/02770903.2013.792347

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Ottanelli R, Rosi E, Romagnoli I, et al. Perception of bronchoconstriction and bronchial hyper-responsiveness in asthma. Clin Sci. 2000;98(6):6817. doi:10.1042/cs0980681

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Papastamelos C, Panitch HB, England SE, Allen JL. Developmental changes in chest wall compliance in infancy and early childhood. J Appl Physiol. 1995;78(1):17984. doi:10.1152/jappl.1995.78.1.179

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):43552. PubMed ID: 22336677 doi:10.1164/rccm.201111-2042ST

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Pianosi P, Pelech A. Stroke volume during exercise in cystic fibrosis. Am J Respir Crit Care Med. 1996;153(3):11059. PubMed ID: 8630552 doi:10.1164/ajrccm.153.3.8630552

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Pianosi P, Smith CP, Almudevar A, McGrath PJ. Dalhousie dyspnea scales: pictorial scales to measure dyspnea during induced bronchoconstriction. Pediatr Pulmonol. 2006;41(12):11827. PubMed ID: 17068820 doi:10.1002/ppul.20512

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Pianosi PT. Flow limitation and dysanapsis in children and adolescents with exertional dyspnea. Respir Physiol Neurobiol. 2018;252-253:5863. PubMed ID: 29588200 doi:10.1016/j.resp.2018.03.013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Pianosi PT, Huebner M, Zhang Z, McGrath PJ. Dalhousie Dyspnea and perceived exertion scales: psychophysical properties in children and adolescents. Respir Physiol Neurobiol. 2014;199:3440. PubMed ID: 24793132 doi:10.1016/j.resp.2014.04.003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Pianosi PT, Huebner M, Zhang Z, Turchetta A, McGrath PJ. Dalhousie pictorial scales measuring dyspnea and perceived exertion during exercise for children and adolescents. Ann Am Thorac Soc. 2015;12(5):71826. PubMed ID: 25695139 doi:10.1513/AnnalsATS.201410-477OC

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Radtke T, Hebestreit H, Gallati S, et al. CFTR genotype and maximal exercise capacity in cystic fibrosis: a cross-sectional study. Ann Am Thorac Soc. 2018;15(2):20916. PubMed ID: 29140739 doi:10.1513/AnnalsATS.201707-570OC

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Robertson CV, Marino FE. A role for the prefrontal cortex in exercise tolerance and termination. J Appl Physiol (1985). 2016;120(4):4646. doi:10.1152/japplphysiol.00363.2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr. 2001;139(3):35965. PubMed ID: 11562614 doi:10.1067/mpd.2001.117288

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Salome CM, Leuppi JD, Freed R, Marks GB. Perception of airway narrowing during reduction of inhaled corticosteroids and asthma exacerbation. Thorax. 2003;58(12):10427. PubMed ID: 14645970 doi:10.1136/thorax.58.12.1042

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Schweitzer C, Marchal F. Dyspnoea in children. Does development alter the perception of breathlessness? Respir Physiol Neurobiol. 2009;167(1):14453. PubMed ID: 19114130 doi:10.1016/j.resp.2008.12.001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59.

    Seear M, Wensley D, West N. How accurate is the diagnosis of exercise induced asthma among Vancouver schoolchildren? Arch Dis Child. 2005;90(9):898902. PubMed ID: 15855180 doi:10.1136/adc.2004.063974

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60.

    Sharma P, Morris NR, Adams L. Effect of induced leg muscle fatigue on exertional dyspnea in healthy subjects. J Appl Physiol. 2015;118(1):4854. doi:10.1152/japplphysiol.00393.2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61.

    Smith JR, Emerson SR, Kurti SP, Gandhi K, Harms CA. Lung volume and expiratory flow rates from pre- to post-puberty. Eur J Appl Physiol. 2015;115(8):164552. PubMed ID: 25761732 doi:10.1007/s00421-015-3149-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    Stark-Leyva KN, Beck KC, Johnson BD. Influence of expiratory loading and hyperinflation on cardiac output during exercise. J Appl Physiol. 2004;96(5):19207. doi:10.1152/japplphysiol.00756.2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Stenekes SJ, Hughes A, Gregoire MC, Frager G, Robinson WM, McGrath PJ. Frequency and self-management of pain, dyspnea, and cough in cystic fibrosis. J Pain Symptom Manage. 2009;38(6):83748. PubMed ID: 19819666 doi:10.1016/j.jpainsymman.2009.04.029

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Still L, Dolen WK. The perception of asthma severity in children. Curr Allergy Asthma Rep. 2016;16(7):50. PubMed ID: 27333779 doi:10.1007/s11882-016-0629-2

  • 65.

    Swain KE, Rosenkranz SK, Beckman B, Harms CA. Expiratory flow limitation during exercise in prepubescent boys and girls: prevalence and implications. J Appl Physiol. 2010;108(5):126774. doi:10.1152/japplphysiol.00123.2009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66.

    Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. The Lancet .1997;349(9052):599603. PubMed ID: 9057731 doi:10.1016/S0140-6736(96)10316-0

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67.

    van Gent R, van Essen-Zandvliet LE, Rovers MM, Kimpen JL, de Meer G, van der Ent CK. Poor perception of dyspnoea in children with undiagnosed asthma. Eur Respir J. 2007;30(5):88791. PubMed ID: 17652315 doi:10.1183/09031936.00031407

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 68.

    Von Leupoldt A, Riedel F, Dahme B. The impact of emotions on the perception of dyspnea in pediatric asthma. Psychophysiology. 2006;43(6):6414. PubMed ID: 17076821 doi:10.1111/j.1469-8986.2006.00453.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 69.

    Wheatley JR, West S, Cala SJ, Engel LA. The effect of hyperinflation on respiratory muscle work in acute induced asthma. Eur Respir J 1990;3(6):62532. PubMed ID: 2379573

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Williams AC, Craig KD. Updating the definition of pain. Pain .2016;157(11):24203. PubMed ID: 27200490 doi:10.1097/j.pain.0000000000000613

  • 71.

    Zutler M, Singer JP, Omachi TA, et al. Relationship of obesity with respiratory symptoms and decreased functional capacity in adults without established COPD. Prim Care Respir J. 2012;21(2):194201. PubMed ID: 22453663 doi:10.4104/pcrj.2012.00028

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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