- Email: [email protected]
Immunotherapy for asthma – Con
Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66
Storms W. Allergens in the pathogenesis of asthma: potential role of antiimmunoglobulin E therapy. Am J Respir Med. 2002:1:361–368. Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J. Longterm budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr 2009; 154: 682–687. van der Heide S, Kauffman HF, Dubois AEJ, et al. Allergen reduction measures in houses of allergic asthmatic patients: effects of air cleaners and allergen-impermeable mattress covers. Eur Respir J. 1997; 10: 1217– 1223.
III.2.2 Immunotherapy for asthma – Con A. Custovic. University of Manchester, UK The efficacy of subcutaneous [1] and sublingual [2] immunotherapy in asthma is modest. This form of treatment is appropriate for allergic asthmatics with mild disease – however, this is the patient group with eosinophillic asthma, who generally responds well to standard anti-inflammatory treatments. Given the efficacy of standard pharmacological treatment and the real risk of adverse effects, the potential small benefits have to be weighed against the side-effects [3]. Not surprisingly British Thoracic Society Guideline on the Management of Asthma does not endorse the use of subcutaneous immunotherapy, and states that “immunotherapy can be considered in patients with asthma where a clinically significant allergen cannot be avoided” [4] but that “the potential for severe allergic reactions to the therapy must be fully discussed with patients” [4]. The BTS guideline is clear about sublingual immunotherapy, stating that “it cannot currently be recommended for the treatment of asthma in routine practice” [4]. It would be important to have evidence to compare the effect of immunotherapy to that of standard pharmacotherapy – unfortunately, such evidence comparing the roles of immunotherapy and pharmacotherapy in the management of asthma is lacking. It has often been stated that immunotherapy offers a possibility to change the natural history of asthma. However, it is important to emphasise that whilst the idea of preventative effect of SIT was suggested by some randomised, controlled (but not placebo controlled) [5] studies, this possible effect is as yet not proven. Thus, more studies are required to establish whether immunotherapy might have a role in primary prophylaxis of asthma [4]. Several different strategies to improve immunotherapy have been evaluated for their safety (e.g. genetically modified hypoallergenic allergen derivatives, recombinant allergens, allergens modified with immunostimulatory DNA sequences composed of unmethylated CpG repeats – allergen/ISS conjugates and peptide immunotherapy) and larger scale-efficacy studies are ongoing. The results of appropriately designed and powered studies are awaited with interest. References [1] Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003(4): CD001186. [2] Calamita Z, Saconato H, Pela AB, Atallah AN. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy 2006; 61(10): 1162–72. [3] Bousquet J, Clark TJ, Hurd S, et al. GINA guidelines on asthma and beyond. Allergy 2007; 62(2): 102–12. [4] British Guideline on the Management of Asthma. Thorax 2008; 63(Suppl 4): iv1–121. [5] Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109(2): 251–6.
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III.3. Obstructive Lung Disease – Pro/Con debate: asthma inflammatory assessment improves asthma care III.3.1 Asthma inflammometry assessment improves asthma care – Pro A. Schuster. Department of Paediatrics, Universit¨ atsklinikum D¨ usseldorf, Germany Bronchial asthma is an inflammatory disease. The crucial therapeutic intervention is anti-inflammatory treatment. Hence, monitoring inflammation (“inflammometry”) is a major diagnostic procedure in the care of asthmatic children. Methods of inflammometry include evaluation of cell profiles in induced sputum, measurements of fractional exhaled nitric oxide concentrations (FeNO), and assessments of mediators in bronchoalveolar lavage (BAL) and in exhaled breath condensate (EBC). Traditional asthma monitoring relies on the history of symptoms, and on lung function tests, including assessments of bronchodilator response and bronchial hyperreactivity. There are shortcomings in all these traditional assessments, and inflammometry has the capacity to add important information to the clinical picture. Certainly, there are differences in the usefulness of the different methods of inflammometry: Analysis of sputum cell profiles may help to define asthma subtypes, and to assess need for anti-inflammatory treatment. However, the method is laborious and time-consuming. For EBC, data are too sparse yet to consider it a useful method for regular care at the time being. BAL may be useful in certain situations, but given its invasiveness, it is reserved for severe cases. In contrast, FeNO measurement is convenient, and it is the method of inflammometry for which considerable data from appropriate paediatric clinical studies have been accumulated. These data show that, apart from being a useful piece of the asthma diagnosis jigsaw, FeNO assessments can help us judge typical situations in asthma management, e.g. after reductions in anti-inflammatory treatment, when FeNO concentrations have been shown to be able to predict imminent loss of asthma control. In that situation, high FeNO concentrations indicate the need for higher doses of anti-inflammatory agents. In other clinical situations, though, the results of FeNO measurements may lead to other actions to be taken, e.g. prompt us to review inhalation technique, or consider a different pharmacologic approach. In any case, FeNO assessments do not replace traditional asthma monitoring methods, but they add valuable information that helps improve asthma care, especially in cases when asthma management is not as easy as prescribing a low-dose inhaled corticosteroid. III.3.2 Asthma inflammometry assessment improves asthma care – Con A. Bush. Department of Paediatric Respirology, Imperial School of Medicine at National Heart and Lung Institute; and Royal Brompton Hospital, UK Correspondence: Correspondence: A. Bush. Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.Tel: +44 207 351 8232; fax: +44 207 351 8763. E-mail: [email protected]
Introduction: There is no doubt that airway inflammation is important and of great research interest, and a PubMed search combining asthma and airway inflammation, limited to humans and the English language yielded nearly 5000 hits. It is generally accepted that asthma is a disease of airway inflammation, and that the most effective treatment is by using the anti-inflammatory effects of inhaled corticosteroids (ICS), so why would one NOT want to measure inflammation? Measurement of airway inflammation in asthma could be useful for: • The diagnosis of asthma • Phenotyping asthma
Storms W. Allergens in the pathogenesis of asthma: potential role of antiimmunoglobulin E therapy. Am J Respir Med. 2002:1:361–368. Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J. Longterm budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr 2009; 154: 682–687. van der Heide S, Kauffman HF, Dubois AEJ, et al. Allergen reduction measures in houses of allergic asthmatic patients: effects of air cleaners and allergen-impermeable mattress covers. Eur Respir J. 1997; 10: 1217– 1223.
III.2.2 Immunotherapy for asthma – Con A. Custovic. University of Manchester, UK The efficacy of subcutaneous [1] and sublingual [2] immunotherapy in asthma is modest. This form of treatment is appropriate for allergic asthmatics with mild disease – however, this is the patient group with eosinophillic asthma, who generally responds well to standard anti-inflammatory treatments. Given the efficacy of standard pharmacological treatment and the real risk of adverse effects, the potential small benefits have to be weighed against the side-effects [3]. Not surprisingly British Thoracic Society Guideline on the Management of Asthma does not endorse the use of subcutaneous immunotherapy, and states that “immunotherapy can be considered in patients with asthma where a clinically significant allergen cannot be avoided” [4] but that “the potential for severe allergic reactions to the therapy must be fully discussed with patients” [4]. The BTS guideline is clear about sublingual immunotherapy, stating that “it cannot currently be recommended for the treatment of asthma in routine practice” [4]. It would be important to have evidence to compare the effect of immunotherapy to that of standard pharmacotherapy – unfortunately, such evidence comparing the roles of immunotherapy and pharmacotherapy in the management of asthma is lacking. It has often been stated that immunotherapy offers a possibility to change the natural history of asthma. However, it is important to emphasise that whilst the idea of preventative effect of SIT was suggested by some randomised, controlled (but not placebo controlled) [5] studies, this possible effect is as yet not proven. Thus, more studies are required to establish whether immunotherapy might have a role in primary prophylaxis of asthma [4]. Several different strategies to improve immunotherapy have been evaluated for their safety (e.g. genetically modified hypoallergenic allergen derivatives, recombinant allergens, allergens modified with immunostimulatory DNA sequences composed of unmethylated CpG repeats – allergen/ISS conjugates and peptide immunotherapy) and larger scale-efficacy studies are ongoing. The results of appropriately designed and powered studies are awaited with interest. References [1] Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003(4): CD001186. [2] Calamita Z, Saconato H, Pela AB, Atallah AN. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy 2006; 61(10): 1162–72. [3] Bousquet J, Clark TJ, Hurd S, et al. GINA guidelines on asthma and beyond. Allergy 2007; 62(2): 102–12. [4] British Guideline on the Management of Asthma. Thorax 2008; 63(Suppl 4): iv1–121. [5] Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109(2): 251–6.
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III.3. Obstructive Lung Disease – Pro/Con debate: asthma inflammatory assessment improves asthma care III.3.1 Asthma inflammometry assessment improves asthma care – Pro A. Schuster. Department of Paediatrics, Universit¨ atsklinikum D¨ usseldorf, Germany Bronchial asthma is an inflammatory disease. The crucial therapeutic intervention is anti-inflammatory treatment. Hence, monitoring inflammation (“inflammometry”) is a major diagnostic procedure in the care of asthmatic children. Methods of inflammometry include evaluation of cell profiles in induced sputum, measurements of fractional exhaled nitric oxide concentrations (FeNO), and assessments of mediators in bronchoalveolar lavage (BAL) and in exhaled breath condensate (EBC). Traditional asthma monitoring relies on the history of symptoms, and on lung function tests, including assessments of bronchodilator response and bronchial hyperreactivity. There are shortcomings in all these traditional assessments, and inflammometry has the capacity to add important information to the clinical picture. Certainly, there are differences in the usefulness of the different methods of inflammometry: Analysis of sputum cell profiles may help to define asthma subtypes, and to assess need for anti-inflammatory treatment. However, the method is laborious and time-consuming. For EBC, data are too sparse yet to consider it a useful method for regular care at the time being. BAL may be useful in certain situations, but given its invasiveness, it is reserved for severe cases. In contrast, FeNO measurement is convenient, and it is the method of inflammometry for which considerable data from appropriate paediatric clinical studies have been accumulated. These data show that, apart from being a useful piece of the asthma diagnosis jigsaw, FeNO assessments can help us judge typical situations in asthma management, e.g. after reductions in anti-inflammatory treatment, when FeNO concentrations have been shown to be able to predict imminent loss of asthma control. In that situation, high FeNO concentrations indicate the need for higher doses of anti-inflammatory agents. In other clinical situations, though, the results of FeNO measurements may lead to other actions to be taken, e.g. prompt us to review inhalation technique, or consider a different pharmacologic approach. In any case, FeNO assessments do not replace traditional asthma monitoring methods, but they add valuable information that helps improve asthma care, especially in cases when asthma management is not as easy as prescribing a low-dose inhaled corticosteroid. III.3.2 Asthma inflammometry assessment improves asthma care – Con A. Bush. Department of Paediatric Respirology, Imperial School of Medicine at National Heart and Lung Institute; and Royal Brompton Hospital, UK Correspondence: Correspondence: A. Bush. Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.Tel: +44 207 351 8232; fax: +44 207 351 8763. E-mail: [email protected]
Introduction: There is no doubt that airway inflammation is important and of great research interest, and a PubMed search combining asthma and airway inflammation, limited to humans and the English language yielded nearly 5000 hits. It is generally accepted that asthma is a disease of airway inflammation, and that the most effective treatment is by using the anti-inflammatory effects of inhaled corticosteroids (ICS), so why would one NOT want to measure inflammation? Measurement of airway inflammation in asthma could be useful for: • The diagnosis of asthma • Phenotyping asthma