Skip to main content
Top
Published in: Indian Journal of Pediatrics 9/2018

01-09-2018 | Review Article

Severe Asthma: Challenges and Pitfalls in Management

Published in: Indian Journal of Pediatrics | Issue 9/2018

Login to get access

Abstract

A small but significant subset of asthmatic children show a lack of response to standard management, resulting in further intensification of therapy to optimise symptom control and may remain symptomatic despite maximal therapy. Severe asthma results in increased risk of adverse outcomes whilst contributing significantly to the economic burden on the nation’s health resources. The ERS / ATS guidelines were published in 2014 and form the basis of identifying, evaluating and managing severe asthmatic children. However, much of this evidence is extrapolated from adult studies and may be inappropriate in children as unlike adults, children have a more atopic phenotype. Severe asthma is an umbrella term and may represent several overlapping heterogeneous wheezing entities. This chapter aims at discussing the strategies employed in managing severe asthmatic children with particular focus on diagnostic challenges and management pitfalls. Particular emphasis is put into the logical and systematic approach to a child with severe asthma and describes the multidisciplinary approach to manage these children. Finally, this chapter describes the novel therapies available in children and in adults in managing this challenging condition.
Literature
1.
go back to reference Lang A, Carlsen KH, Haaland G, et al. Severe asthma in childhood: assessed in 10 year olds in a birth cohort study. Allergy. 2008;63:1054–60.CrossRefPubMed Lang A, Carlsen KH, Haaland G, et al. Severe asthma in childhood: assessed in 10 year olds in a birth cohort study. Allergy. 2008;63:1054–60.CrossRefPubMed
2.
go back to reference Nordlund B, Melén E, Schultz ES, Grönlund H, Hedlin G, Kull I. Prevalence of severe childhood asthma according to the WHO. Respir Med. 2014;108:1234–7.CrossRefPubMed Nordlund B, Melén E, Schultz ES, Grönlund H, Hedlin G, Kull I. Prevalence of severe childhood asthma according to the WHO. Respir Med. 2014;108:1234–7.CrossRefPubMed
3.
go back to reference Fleming L, Wilson N, Bush A. Difficult to control asthma in children. Curr Opin Allergy Clin Immunol. 2007;7:190–5.CrossRefPubMed Fleming L, Wilson N, Bush A. Difficult to control asthma in children. Curr Opin Allergy Clin Immunol. 2007;7:190–5.CrossRefPubMed
4.
go back to reference Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–73.CrossRefPubMed Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–73.CrossRefPubMed
6.
go back to reference Hedlin G, Bush A, Carlsen KL, et al. Problematic severe asthma in children, not one problem but many: a GA2LEN initiative. Eur Respir J. 2010;36:196–201.CrossRefPubMed Hedlin G, Bush A, Carlsen KL, et al. Problematic severe asthma in children, not one problem but many: a GA2LEN initiative. Eur Respir J. 2010;36:196–201.CrossRefPubMed
8.
go back to reference Cook J, Beresford F, Fainardi V, et al. Managing the pediatric patient with refractory asthma: a multidisciplinary approach. J Asthma Allergy. 2017;10:123–30.CrossRefPubMedPubMedCentral Cook J, Beresford F, Fainardi V, et al. Managing the pediatric patient with refractory asthma: a multidisciplinary approach. J Asthma Allergy. 2017;10:123–30.CrossRefPubMedPubMedCentral
9.
go back to reference Ramratnam SK, Bacharier LB, Guilbert TW. Severe asthma in children. J Allergy Clin Immunol Pract. 2017;5:889–98.CrossRefPubMed Ramratnam SK, Bacharier LB, Guilbert TW. Severe asthma in children. J Allergy Clin Immunol Pract. 2017;5:889–98.CrossRefPubMed
10.
11.
go back to reference Fleming L, Murray C, Bansal AT, et al. The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts. Eur Respir J. 2015;46:1322–33.CrossRefPubMed Fleming L, Murray C, Bansal AT, et al. The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts. Eur Respir J. 2015;46:1322–33.CrossRefPubMed
14.
go back to reference Kelly YJ, Brabin BJ, Milligan PJ, Reid JA, Heaf D, Pearson MG. Clinical significance of cough and wheeze in the diagnosis of asthma. Arch Dis Child. 1996;75:489–93.CrossRefPubMedPubMedCentral Kelly YJ, Brabin BJ, Milligan PJ, Reid JA, Heaf D, Pearson MG. Clinical significance of cough and wheeze in the diagnosis of asthma. Arch Dis Child. 1996;75:489–93.CrossRefPubMedPubMedCentral
17.
go back to reference Levy DML, Godfrey S, Irving CS, et al. Wheeze detection: recordings vs. assessment of physician and parent. J Asthma. 2004;41:845–53.CrossRefPubMed Levy DML, Godfrey S, Irving CS, et al. Wheeze detection: recordings vs. assessment of physician and parent. J Asthma. 2004;41:845–53.CrossRefPubMed
18.
go back to reference Saglani S, McKenzie S, Bush A, Payne D. A video questionnaire identifies upper airway abnormalities in preschool children with reported wheeze. Arch Dis Child. 2005;90:961–4.CrossRefPubMedPubMedCentral Saglani S, McKenzie S, Bush A, Payne D. A video questionnaire identifies upper airway abnormalities in preschool children with reported wheeze. Arch Dis Child. 2005;90:961–4.CrossRefPubMedPubMedCentral
20.
go back to reference 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;70:57–63.CrossRefPubMed 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;70:57–63.CrossRefPubMed
21.
go back to reference Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319–38.CrossRefPubMed Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319–38.CrossRefPubMed
23.
25.
go back to reference Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF, Sorkness CA. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426–32.CrossRefPubMed Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF, Sorkness CA. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426–32.CrossRefPubMed
26.
go back to reference Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM. Gender-dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol. 2011;127:1073–4.CrossRefPubMedPubMedCentral Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM. Gender-dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol. 2011;127:1073–4.CrossRefPubMedPubMedCentral
27.
go back to reference Maitra A. Assessment of airway inflammation. In: Lodha R, Kabra SK, editors. Essential Pediatric Pulmonology, 3rd ed. New Delhi: Jaypee Brothers; 2018. p. 428. Maitra A. Assessment of airway inflammation. In: Lodha R, Kabra SK, editors. Essential Pediatric Pulmonology, 3rd ed. New Delhi: Jaypee Brothers; 2018. p. 428.
28.
go back to reference Gibson P, Simpson J, Hankin R, Powell H, Henry R. Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma. Thorax. 2003;58:116–21.CrossRefPubMedPubMedCentral Gibson P, Simpson J, Hankin R, Powell H, Henry R. Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma. Thorax. 2003;58:116–21.CrossRefPubMedPubMedCentral
29.
go back to reference Bossley CJ, Fleming L, Gupta A, et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. J Allergy Clin Immunol. 2012;129:974–82.e13.CrossRefPubMedPubMedCentral Bossley CJ, Fleming L, Gupta A, et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. J Allergy Clin Immunol. 2012;129:974–82.e13.CrossRefPubMedPubMedCentral
30.
go back to reference Low K, Lau KK, Holmes P, et al. Abnormal vocal cord function in difficult-to-treat asthma. Am J Respir Crit Care Med. 2011;184:50–6.CrossRefPubMed Low K, Lau KK, Holmes P, et al. Abnormal vocal cord function in difficult-to-treat asthma. Am J Respir Crit Care Med. 2011;184:50–6.CrossRefPubMed
31.
go back to reference Mehlum CS, Walsted ES, Godballe C, Backer V. Supraglottoplasty as treatment of exercise induced laryngeal obstruction (EILO). Eur Arch Otorhinolaryngol. 2016;273:945–51.CrossRefPubMed Mehlum CS, Walsted ES, Godballe C, Backer V. Supraglottoplasty as treatment of exercise induced laryngeal obstruction (EILO). Eur Arch Otorhinolaryngol. 2016;273:945–51.CrossRefPubMed
34.
go back to reference Carroll CL, Stoltz P, Raykov N, Smith SR, Zucker AR. Childhood overweight increases hospital admission rates for asthma. Pediatrics. 2007;120:734–40.CrossRefPubMed Carroll CL, Stoltz P, Raykov N, Smith SR, Zucker AR. Childhood overweight increases hospital admission rates for asthma. Pediatrics. 2007;120:734–40.CrossRefPubMed
35.
go back to reference Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedón JC. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011;127:741–9.CrossRefPubMedPubMedCentral Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedón JC. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011;127:741–9.CrossRefPubMedPubMedCentral
36.
go back to reference Kouzouna A, Gilchrist FJ, Ball V, et al. A systematic review of early life factors which adversely affect subsequent lung function. Paediatr Respir Rev. 2016;20:67–75.PubMed Kouzouna A, Gilchrist FJ, Ball V, et al. A systematic review of early life factors which adversely affect subsequent lung function. Paediatr Respir Rev. 2016;20:67–75.PubMed
37.
39.
go back to reference van Huisstede A, Rudolphus A, Castro Cabezas M, et al. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax. 2015;70:659–67.CrossRefPubMed van Huisstede A, Rudolphus A, Castro Cabezas M, et al. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax. 2015;70:659–67.CrossRefPubMed
40.
go back to reference Roberts G, Patel N, Levi-Schaffer F, Habibi P, Lack G. Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study. J Allergy Clin Immunol. 2003;112:168–74.CrossRefPubMed Roberts G, Patel N, Levi-Schaffer F, Habibi P, Lack G. Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study. J Allergy Clin Immunol. 2003;112:168–74.CrossRefPubMed
41.
go back to reference Murray CS, Poletti G, Kebadze T, et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006;61:376–82.CrossRefPubMed Murray CS, Poletti G, Kebadze T, et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006;61:376–82.CrossRefPubMed
42.
go back to reference Morgan WJ, Crain EF, Gruchalla RS, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med. 2004;351:1068–80.CrossRefPubMed Morgan WJ, Crain EF, Gruchalla RS, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med. 2004;351:1068–80.CrossRefPubMed
43.
go back to reference de Groot EP, Nijkamp A, Duiverman EJ, Brand PLP. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax. 2012;67:582–7.CrossRefPubMed de Groot EP, Nijkamp A, Duiverman EJ, Brand PLP. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax. 2012;67:582–7.CrossRefPubMed
44.
45.
go back to reference Lang JE, Hossain J, Holbrook JT, et al. Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution? Thorax. 2016;71:238–46.CrossRefPubMed Lang JE, Hossain J, Holbrook JT, et al. Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution? Thorax. 2016;71:238–46.CrossRefPubMed
47.
go back to reference Bracken M, Fleming L, Hall P, et al. The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child. 2009;94:780–4.CrossRefPubMed Bracken M, Fleming L, Hall P, et al. The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child. 2009;94:780–4.CrossRefPubMed
48.
go back to reference Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011;105:930–8.CrossRefPubMed Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011;105:930–8.CrossRefPubMed
49.
go back to reference Sleath B, Ayala GX, Gillette C, et al. Provider demonstration and assessment of child device technique during pediatric asthma visits. Pediatrics. 2011;127:642–8.CrossRefPubMedPubMedCentral Sleath B, Ayala GX, Gillette C, et al. Provider demonstration and assessment of child device technique during pediatric asthma visits. Pediatrics. 2011;127:642–8.CrossRefPubMedPubMedCentral
50.
51.
go back to reference Peat JK, Keena V, Harakeh Z, Marks G. Parental smoking and respiratory tract infections in children. Paediatr Respir Rev. 2001;2:207–13.PubMed Peat JK, Keena V, Harakeh Z, Marks G. Parental smoking and respiratory tract infections in children. Paediatr Respir Rev. 2001;2:207–13.PubMed
52.
go back to reference Searing DA, Rabinovitch N. Environmental pollution and lung effects in children. Curr Opin Pediatr. 2011;23:314–8.CrossRefPubMed Searing DA, Rabinovitch N. Environmental pollution and lung effects in children. Curr Opin Pediatr. 2011;23:314–8.CrossRefPubMed
53.
go back to reference Sales J, Fivush R, Teague GW. The role of parental coping in children with asthma’s psychological well-being and asthma-related quality of life. J Pediatr Psychol. 2008;33:208–19.CrossRefPubMed Sales J, Fivush R, Teague GW. The role of parental coping in children with asthma’s psychological well-being and asthma-related quality of life. J Pediatr Psychol. 2008;33:208–19.CrossRefPubMed
54.
go back to reference Barnes PJ. Neuroeffector mechanisms: the interface between inflammation and neuronal responses. J Allergy Clin Immunol. 1996;98:S73–81; discussion S81–3.CrossRefPubMed Barnes PJ. Neuroeffector mechanisms: the interface between inflammation and neuronal responses. J Allergy Clin Immunol. 1996;98:S73–81; discussion S81–3.CrossRefPubMed
55.
go back to reference Rosenkranz MA, Busse WW, Sheridan JF, Crisafi GM, Davidson RJ. Are there neurophenotypes for asthma? Functional brain imaging of the interaction between emotion and inflammation in asthma. PLoS One. 2012;7:e40921.CrossRefPubMedPubMedCentral Rosenkranz MA, Busse WW, Sheridan JF, Crisafi GM, Davidson RJ. Are there neurophenotypes for asthma? Functional brain imaging of the interaction between emotion and inflammation in asthma. PLoS One. 2012;7:e40921.CrossRefPubMedPubMedCentral
57.
go back to reference Sandberg S, Paton JY, Ahola S, et al. The role of acute and chronic stress in asthma attacks in children. Lancet. 2000;356:982–7.CrossRefPubMed Sandberg S, Paton JY, Ahola S, et al. The role of acute and chronic stress in asthma attacks in children. Lancet. 2000;356:982–7.CrossRefPubMed
58.
go back to reference Lietzén R, Virtanen P, Kivimäki M, Sillanmäki L, Vahtera J, Koskenvuo M. Stressful life events and the onset of asthma. Eur Respir J. 2011;37:1360–5.CrossRefPubMed Lietzén R, Virtanen P, Kivimäki M, Sillanmäki L, Vahtera J, Koskenvuo M. Stressful life events and the onset of asthma. Eur Respir J. 2011;37:1360–5.CrossRefPubMed
59.
go back to reference Yorke J, Shuldham C. Family therapy for chronic asthma in children. Cochrane Database Syst Rev. 2005;2:CD000089. Yorke J, Shuldham C. Family therapy for chronic asthma in children. Cochrane Database Syst Rev. 2005;2:CD000089.
60.
go back to reference Fitzpatrick AM, Teague WG, Meyers DA, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institute of Health/National Heart, Lung and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011;127:382–9.e1-13.CrossRefPubMed Fitzpatrick AM, Teague WG, Meyers DA, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institute of Health/National Heart, Lung and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011;127:382–9.e1-13.CrossRefPubMed
61.
go back to reference Howrylak JA, Fuhlbrigge AL, Strunk RC, Zeiger RS, Weiss ST, Raby BA. Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications. J Allergy Clin Immunol. 2014;133:1289–300, 1300.e1-12. Howrylak JA, Fuhlbrigge AL, Strunk RC, Zeiger RS, Weiss ST, Raby BA. Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications. J Allergy Clin Immunol. 2014;133:1289–300, 1300.e1-12.
63.
go back to reference Liu AH, Babineau DC, Krouse RZ, et al. Pathways through which asthma risk factors contribute to asthma severity in inner-city children. J Allergy Clin Immunol. 2016;138:1042–50.CrossRefPubMedPubMedCentral Liu AH, Babineau DC, Krouse RZ, et al. Pathways through which asthma risk factors contribute to asthma severity in inner-city children. J Allergy Clin Immunol. 2016;138:1042–50.CrossRefPubMedPubMedCentral
64.
go back to reference Bossley CJ, Fleming L, Ullmann N, et al. Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach. J Allergy Clin Immunol. 2016;138:413–20.e6.CrossRefPubMed Bossley CJ, Fleming L, Ullmann N, et al. Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach. J Allergy Clin Immunol. 2016;138:413–20.e6.CrossRefPubMed
65.
go back to reference Jutel M, Agache I, Bonini S, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556–68.CrossRefPubMed Jutel M, Agache I, Bonini S, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556–68.CrossRefPubMed
66.
go back to reference Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108:E36.CrossRefPubMed Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108:E36.CrossRefPubMed
67.
go back to reference Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005–15.CrossRefPubMedPubMedCentral Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005–15.CrossRefPubMedPubMedCentral
68.
go back to reference Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017;9:CD010834.PubMed Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017;9:CD010834.PubMed
69.
go back to reference Rodrigo GJ, Castro-Rodríguez 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.CrossRefPubMed Rodrigo GJ, Castro-Rodríguez 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.CrossRefPubMed
70.
go back to reference Hamelmann E, Bateman ED, Vogelberg C, 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.e8.CrossRefPubMed Hamelmann E, Bateman ED, Vogelberg C, 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.e8.CrossRefPubMed
71.
go back to reference Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–66.CrossRefPubMed Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–66.CrossRefPubMed
72.
go back to reference Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936–46.CrossRefPubMed Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936–46.CrossRefPubMed
73.
go back to reference Gauvreau GM, Boulet L-P, Leigh R, et al. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015;191:161–7.CrossRefPubMed Gauvreau GM, Boulet L-P, Leigh R, et al. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015;191:161–7.CrossRefPubMed
74.
go back to reference Gonem S, Berair R, Singapuri A, et al. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre,s randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2016;4:699–707.CrossRefPubMed Gonem S, Berair R, Singapuri A, et al. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre,s randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2016;4:699–707.CrossRefPubMed
75.
go back to reference Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev. 2014;3:CD009910. Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev. 2014;3:CD009910.
Metadata
Title
Severe Asthma: Challenges and Pitfalls in Management
Publication date
01-09-2018
Published in
Indian Journal of Pediatrics / Issue 9/2018
Print ISSN: 0019-5456
Electronic ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2686-0

Other articles of this Issue 9/2018

Indian Journal of Pediatrics 9/2018 Go to the issue