World Health Organization. Asthma. Fact sheet 307. Updated 2017. http://www.who.int/mediacentre/factsheets/fs307/en/. Accessed 1 Jul 2017.
Asthma UK. Asthma facts and FAQs. http://www.asthma.org.uk/about/media/facts-and-statistics/. Accessed 14 Nov 2017.
Schmier JK, Manjunath R, Halpern MT, Jones ML, Thompson K, Diette GB. The impact of inadequately controlled asthma in urban children on quality of life and productivity. Ann Allergy Asthma Immunol. 2007;98:245–51.
Article
PubMed
Google Scholar
Global Initiative for Asthma. Global strategy for asthma management and prevention. http://ginasthma.org/gina-reports/. Accessed 9 Mar 2017.
Custovic A, Johnston SL, Pavord I, Gaga M, Fabbri L, Bel EH, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy. 2013;68:1520–31.
CAS
Article
PubMed
Google Scholar
Belgrave DC, Buchan I, Bishop C, Lowe L, Simpson A, Custovic A. Trajectories of lung function during childhood. Am J Respir Crit Care Med. 2014;189:1101–9.
Article
PubMed
PubMed Central
Google Scholar
Rodrigo GJ, Neffen H. A systematic review of the efficacy and safety of a fixed-dose combination of umeclidinium and vilanterol for the treatment of COPD. Chest. 2015;148:397–407.
Article
PubMed
Google Scholar
Cazzola M, Ora J, Rogliani P, Matera MG. Role of muscarinic antagonists in asthma therapy. Expert Rev Respir Med. 2017;11:239–53.
CAS
Article
PubMed
Google Scholar
Griffiths B, Ducharme FM. Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev. 2013;(8):CD000060.
Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005;60:740–6.
CAS
Article
PubMed
PubMed Central
Google Scholar
Canning BJ. Reflex regulation of airway smooth muscle tone. J Appl Physiol (1985). 2006;101:971–85.
CAS
Article
Google Scholar
Vogelberg C. Emerging role of long-acting anticholinergics in children with asthma. Curr Opin Pulm Med. 2016;22:74–9.
CAS
Article
PubMed
Google Scholar
Hashimoto A, Maeda H, Yokoyama M. Augmentation of parasympathetic nerve function in patients with extrinsic bronchial asthma: evaluation by coefficiency of variance of R-R interval with modified long-term ECG monitoring system. Kobe J Med Sci. 1996;42:347–59.
CAS
PubMed
Google Scholar
Novelli F, Malagrino L, Dente FL, Paggiaro P. Efficacy of anticholinergic drugs in asthma. Expert Rev Respir Med. 2012;6:309–19.
CAS
Article
PubMed
Google Scholar
Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006;7:73.
Article
PubMed
PubMed Central
Google Scholar
Barnes PJ. The pharmacological properties of tiotropium. Chest. 2000;117(Suppl. 2):63S–6S.
CAS
Article
PubMed
Google Scholar
Disse B, Speck GA, Rominger KL, Witek TJ Jr, Hammer R. Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci. 1999;64:457–64.
CAS
Article
PubMed
Google Scholar
Haddad EB, Mak JC, Barnes PJ. Characterization of [3H]Ba 679 BR, a slowly dissociating muscarinic antagonist, in human lung: radioligand binding and autoradiographic mapping. Mol Pharmacol. 1994;45:899–907.
CAS
PubMed
Google Scholar
Meurs H, Oenema TA, Kistemaker LE, Gosens R. A new perspective on muscarinic receptor antagonism in obstructive airways diseases. Curr Opin Pharmacol. 2013;13:316–23.
CAS
Article
PubMed
Google Scholar
Radovanovic D, Santus P, Blasi F, Mantero M. The evidence on tiotropium bromide in asthma: from the rationale to the bedside. Multidiscip Respir Med. 2017;12:17.
Article
PubMed
PubMed Central
Google Scholar
Halpin DM, Kaplan AG, Russell RK. Why choose tiotropium for my patient? A comprehensive review of actions and outcomes versus other bronchodilators. Respir Med. 2017;128:28–41.
Article
PubMed
Google Scholar
Bos IS, Gosens R, Zuidhof AB, Schaafsma D, Halayko AJ, Meurs H, et al. Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison. Eur Respir J. 2007;30:653–61.
CAS
Article
PubMed
Google Scholar
Ohta S, Oda N, Yokoe T, Tanaka A, Yamamoto Y, Watanabe Y, et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010;40:1266–75.
CAS
Article
PubMed
Google Scholar
Halpin DM. Tiotropium in asthma: what is the evidence and how does it fit in? World Allergy Organ J. 2016;9:29.
Article
PubMed
PubMed Central
Google Scholar
Novelli F, Costa F, Latorre M, Malagrino L, Celi A, Vagaggini B, et al. Tiotropium: a new therapeutic option in asthma. Monaldi Arch Chest Dis. 2013;79:109–15.
CAS
Article
PubMed
Google Scholar
Paggiaro P, Halpin DM, Buhl R, Engel M, Zubek VB, Blahova Z, et al. The effect of tiotropium in symptomatic asthma despite low- to medium-dose inhaled corticosteroids: a randomized controlled trial. J Allergy Clin Immunol Pract. 2016;4:104–13.
Article
PubMed
Google Scholar
Kerstjens HA, Casale TB, Bleecker ER, Meltzer EO, Pizzichini E, Schmidt O, et al. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med. 2015;3:367–76.
CAS
Article
PubMed
Google Scholar
Ohta K, Ichinose M, Tohda Y, Engel M, Moroni-Zentgraf P, Kunimitsu S, et al. Long-term once-daily tiotropium Respimat® is well tolerated and maintains efficacy over 52 weeks in patients with symptomatic asthma in Japan: a randomised, placebo-controlled study. PLoS One. 2015;10:e0124109.
Article
PubMed
PubMed Central
Google Scholar
Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367:1198–207.
CAS
Article
PubMed
Google Scholar
Dahl R, Engel M, Dusser D, Halpin D, Kerstjens HA, Zaremba-Pechmann L, et al. Safety and tolerability of once-daily tiotropium Respimat® as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: a pooled safety analysis. Respir Med. 2016;118:102–11.
Article
PubMed
Google Scholar
Vogelberg C, Engel M, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Downie J, et al. Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study. Respir Med. 2014;108:1268–76.
Article
PubMed
Google Scholar
Vogelberg C, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Hamelmann E, Engel M, et al. A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015;16:20.
CAS
Article
PubMed
PubMed Central
Google Scholar
Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, et al. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138:441–50.
CAS
Article
PubMed
Google Scholar
Hamelmann E, Bernstein JA, Vandewalker M, Moroni-Zentgraf P, Verri D, Unseld A, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1601100.
Article
PubMed
PubMed Central
Google Scholar
Schmidt O, Hamelmann E, Vogelberg C, Laki I, El Azzi G, Engel M, et al. Once-daily tiotropium Respimat® add-on therapy improves lung function in children with moderate symptomatic asthma. Eur Respir J. 2016;48 (Suppl. 60):PA4398.
Szefler SJ, Murphy K, Harper T, Boner A, Laki I, Engel M, et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. J Allergy Clin Immunol. 2017;140:1277–87.
CAS
Article
PubMed
Google Scholar
Vrijlandt E, El Azzi G, El Azzi G, Vandewalker M, Rupp N, Harper T, et al. Safety and efficacy of tiotropium in 1–5-year-old children with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018. (in press).
Rodrigo GJ, Neffen H. Efficacy and safety of tiotropium in school-age children with moderate to severe symptomatic asthma: a systematic review. Pediatr Allergy Immunol. 2017;26:551–6.
Article
Google Scholar
Rodrigo GJ, Castro-Rodriguez JA. Tiotropium for the treatment of adolescents with moderate to severe symptomatic asthma: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2015;115:211–6.
CAS
Article
PubMed
Google Scholar
Vogelberg C, Laki I, Schmidt O, Hamelmann E, El Azzi G, Engel M, et al. Safety and tolerability of once-daily tiotropium Respimat® add-on therapy in children with moderate symptomatic asthma. Eur Respir J. 2016;48 (Suppl. 60):PA4399.
Vogelberg C, Hamelmann E, Szefler S, El Azzi G, Moroni-Zentgraf P, Engel M, et al. Once-daily tiotropium Respimat add-on therapy improves lung function and control in adolescents and children with moderate symptomatic asthma. J Allergy Clin Immunol. 2017;139(2):AB95.
Article
Google Scholar
Vandewalker M, Hamelmann E, Engel M, El Azzi G, Moroni-Zentgraf P, Unseld A, et al. Once daily tiotropium Respimat add-on therapy has a safety profile comparable with placebo in children and adolescents. J Allergy Clin Immunol. 2017;139(2):AB94.
Article
Google Scholar
Hamelmann E, Vogelberg C, Goldstein S, El Azzi G, Engel M, Sigmund R, et al. Once-daily tiotropium Respimat add-on therapy improves lung function in patients aged 6–17 years with severe symptomatic asthma. Pediatr Pulmonol. 2017;52(S46):S100–S176.
Vogelberg C, Hamelmann E, Vrijlandt E, Engel M, El Azzi G, Moroni-Zentgraf P, et al. Tiotropium add-on therapy has a safety profile comparable with that of placebo in children and adolescents with symptomatic asthma. Allergy. 2017;72(S103):414.
Google Scholar
Morton RW, Everard ML, Elphick HE. Adherence in childhood asthma: the elephant in the room. Arch Dis Child. 2014;99:949–53.
Article
PubMed
Google Scholar
Boonsawat W, Goryachkina L, Jacques L, Frith L. Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma: a placebo-controlled comparison. Clin Drug Investig. 2008;28:101–11.
CAS
Article
PubMed
Google Scholar
Diette GB, Markson L, Skinner EA, Nguyen TT, Algatt-Bergstrom P, Wu AW. Nocturnal asthma in children affects school attendance, school performance, and parents’ work attendance. Arch Pediatr Adolesc Med. 2000;154:923–8.
CAS
Article
PubMed
Google Scholar
Stores G, Ellis AJ, Wiggs L, Crawford C, Thomson A. Sleep and psychological disturbance in nocturnal asthma. Arch Dis Child. 1998;78:413–9.
CAS
Article
PubMed
PubMed Central
Google Scholar
Gustafsson D, Olofsson N, Andersson F, Lindberg B, Schollin J. Intervention models on psycho-social health in families with an asthmatic child. Pediatr Allergy Immunol. 2000;11:241–5.
CAS
Article
PubMed
Google Scholar
Kerstjens HA, Moroni-Zentgraf P, Tashkin DP, Dahl R, Paggiaro P, Vandewalker M, et al. Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status. Respir Med. 2016;117:198–206.
Article
PubMed
Google Scholar
Hamelmann E, Vogelberg C, Voelker B, El Azzi G, Engel M, Sigmund R, Szefler SJ. Tiotropium add-on therapy improves lung function in children and adolescents with moderate and severe symptomatic asthma, independent of markers of allergic status. Allergy. 2017;72:S103.
Google Scholar
Vogelberg C, Halpin D, Voelker B, Engel M, Luehmann, Hamelmann E. Once-daily tiotropium Respimat® add-on therapy improves lung function in children with moderate symptomatic asthma, independent of the degree of airflow obstruction. Eur Respir J. 2017;50:4040.
Google Scholar
Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R, et al. Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol. 2013;132:1068–74.e1.
Google Scholar
Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836–44.
Article
PubMed
Google Scholar
McGeachie MJ, Yates KP, Zhou X, Guo F, Sternberg AL, Van Natta ML, et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016;374:1842–52.
CAS
Article
PubMed
PubMed Central
Google Scholar
Wu AC, Gregory M, Kymes S, Lambert D, Edler J, Stwalley D, et al. Modeling asthma exacerbations through lung function in children. J Allergy Clin Immunol. 2012;130:1065–70.
Article
PubMed
PubMed Central
Google Scholar
Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW, et al. FEV(1) is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. 2001;107:61–7.
CAS
Article
PubMed
Google Scholar
Teach SJ, Gergen PJ, Szefler SJ, Mitchell HE, Calatroni A, Wildfire J, et al. Seasonal risk factors for asthma exacerbations among inner-city children. J Allergy Clin Immunol. 2015;135:146–73.e5.
Google Scholar
Yawn BP. The role of the primary care physician in helping adolescent and adult patients improve asthma control. Mayo Clin Proc. 2011;86:894–902.
Article
PubMed
PubMed Central
Google Scholar
de Benedictis D, Bush A. Asthma in adolescence: is there any news? Pediatr Pulmonol. 2017;52:129–38.
Article
PubMed
Google Scholar
Schaefer MR, Kavookjian J. The impact of motivational interviewing on adherence and symptom severity in adolescents and young adults with chronic illness: a systematic review. Patient Educ Couns. 2017;100(12):2190–9.
Article
PubMed
Google Scholar
Gibson PG, Powell H, Coughlan J, Wilson AJ, Abramson M, Haywood P, et al. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev. 2002;(1):CD001117.
Campbell JD, Brooks M, Hosokawa P, Robinson J, Song L, Krieger J. Community health worker home visits for Medicaid-enrolled children with asthma: effects on asthma outcomes and costs. Am J Public Health. 2015;105:2366–72.
Article
PubMed
PubMed Central
Google Scholar
Partridge MR, Caress AL, Brown C, Hennings J, Luker K, Woodcock A, et al. Can lay people deliver asthma self-management education as effectively as primary care based practice nurses? Thorax. 2008;63:778–83.
CAS
Article
PubMed
Google Scholar
Burgess S, Sly P, Devadason S. Adherence with preventive medication in childhood asthma. Pulm Med. 2011;2011:973849.
Article
PubMed
PubMed Central
Google Scholar
Navaratnam P, Friedman HS, Urdaneta E. The impact of adherence and disease control on resource use and charges in patients with mild asthma managed on inhaled corticosteroid agents. Patient Prefer Adherence. 2010;4:197–205.
CAS
PubMed
PubMed Central
Google Scholar
De Simoni A, Horne R, Fleming L, Bush A, Griffiths C. What do adolescents with asthma really think about adherence to inhalers? Insights from a qualitative analysis of a UK online forum. BMJ Open. 2017;7:e015245.
PubMed
PubMed Central
Google Scholar
Kamin W, Frank M, Kattenbeck S, Moroni-Zentgraf P, Wachtel H, Zielen S. A handling study to assess use of the Respimat® Soft Mist™ Inhaler in children under 5 years old. J Aerosol Med Pulm Drug Deliv. 2015;28:372–81.
Article
PubMed
PubMed Central
Google Scholar
Dalby R, Spallek M, Voshaar T. A review of the development of Respimat Soft Mist Inhaler. Int J Pharm. 2004;283:1–9.
CAS
Article
PubMed
Google Scholar
Dalby RN, Eicher J, Zierenberg B. Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders. Med Devices (Auckl). 2011;4:145–55.
CAS
PubMed
PubMed Central
Google Scholar
Anderson WC 3rd, Szefler SJ. New and future strategies to improve asthma control in children. J Allergy Clin Immunol. 2015;136:848–59.
Article
PubMed
Google Scholar
Buels KS, Fryer AD. Muscarinic receptor antagonists: effects on pulmonary function. Handb Exp Pharmacol. 2012;208:317–41.
CAS
Article
Google Scholar
Barnes P. Muscarinic receptor subtypes in airways. Eur Respir J. 1993;6:328–31.
CAS
PubMed
Google Scholar