XXXII Congresso Sezione SIAAIC Toscana XI Congresso Sezione SIAAIC Toscana, Emilia Romagna e San Marino IV Congresso Sezione SIAAIC Umbria e Marche Convitu tuo della Calza Firenze 11-12 novembre 2016 I SESSIONE: LA PATOLOGIA OSTRUTTIVA BRONCHIALE Ancora mortj tj per asma: le tante opzioni della terapia tradizionale MARCELLO MONTAGNI U.O.D. Allergologia Ospedale G. da Saliceto, Piacenza
Death due to asthma Asthma is a serious global health problem afgectjng at least 300 million people, with a high global burden of disability. Since 1990 mortality rates for asthma have been falling but despite major advances in the treatment of asthma and the development of several asthma guidelines over the past decades, people stjll die of asthma currently. Asthma ranks 35 th as a cause of death worldwide.
CDC Number of deaths from selected causes Asthma (all ages): 3630 Death rates for selected causes Asthma (all ages): 1.1/100.000
Natj tjonal surveillance of asthma: United States, 2001- 2010. CDC Moorman JE et al. Vital Health Stat 3. 2012 Among subjects with asthma, the rate of asthma deaths decreased from 2.1/10.000 persons in 2001 to 1.4/10.000 persons in 2009. Fatalitjes from asthma most commonly occur in lower income, non-white, urban populatjons.
htup://www.worldlifeexpectancy.com/cause-of-death/asthma/by-country (Accessed on November 8, 2016)
Wo World Map of the Proportj tjon of the Populatj tjon with Access to Essentj tjal Drugs Masoli M, Fabian D, Holt S, et al. Global Burden of Asthma. 2004, Global Initjatjve for Asthma
AJRCCM 2006 In-hospital asthma mortality was 0.5% (99% confj fjdence interval [CI], 0.4–0.6), with mean hospital stay of 2.7 d (99% CI, 2.6–2.8 d). In multj tjvariable analyses, there were no signifj fjcant race difg fgerences in hospital deaths.
2013
2015 Reasons for asthma deaths between 2005 and 2009 were investjgated. Coroner’s fjndings, autopsy, toxicology and police reports were reviewed to determine if the death was due to asthma. 243/283 (85%) deaths were due to asthma rather than having asthma as a comorbidity when another immediate cause of death existed. We identjfjed preventable or modifjable factors in 70% of these deaths. Even in the modern treatment era with an emphasis on inhaled glucocortjcoids, mortality among asthmatjc patjents is mainly due to asthma.
Respiratory Research 2016 Current smokers 20% Obesity 31%
Respiratory Research 2016
Slow onset fatal asthma Rapid onset fatal asthma VS Approximately 80 to 85 % of patjents Up to 20 % death occurs less than 2 to 6 hours who die of asthma have a history of afuer symptom onset. progressive symptoms for more than 12 hours. severe airway obstructjon mainly due to eosinophilic infmammatjon and obstructjon smooth muscle bronchospasm and neutrophils of airway lumens by tenacious mucus and are the predominant infmammatory cell in the desquamated epithelium. airway mucosa.
Multjdisciplinary Respiratory Medicine 2016 AEROALLERGENS A trigger of fatal and near fatal asthma was identjfjed in mould sensitjvity. The prevalence of sensitjsatjon to moulds (Alternaria alternate or Cladosporium herbarum, or both) increased with increasing severity of asthma. Sensitjsatjon to moulds has been associated with increased asthma severity and death, hospital admission and intensive care admissions in adults and with increased bronchial reactjvity in children. In a study during the pollen season, mean concentratjons of mould spores, but not of tree, grass, or ragweed pollen, were signifjcantly higher on the days when there were deaths related to asthma than on the days when no such deaths occurred. Aspirin? Exercise?
2012
History of hospital (OR=2.62, 95% CI 1.04 to 6.58, P=0.04) and/or intensive care unit (OR=5.14, 95% CI 1.91 to 13.86, P=0.001) admissions and mechanical ventjlatjon (OR=6.69, 95% CI 2.80 to 15.97, P=0.0001) due to asthma were predictors of NFA and FA.
2016 update Factors that increase the risk of asthma-related death • A history of near-fatal asthma requiring intubatjon and mechanical ventjlatjon • Hospitalizatjon or emergency care visit for asthma in the past year • Currently using or having recently stopped using oral cortj tjcosteroids (a marker of event severity) • Not currently using inhaled cortj tjcosteroids • Over-use of SABAs, especially use of more than one canister of salbutamol (or equivalent) monthly • A history of psychiatric disease or psychosocial problems • Poor adherence with asthma medicatj tjons and/or poor adherence with (or lack of) a writuen asthma actjon plan • Food allergy in a patjent with asthma
JACI 2001 The widespread and progressive increase in the use of ICS therapy over the past 20 to 30 years has decreased asthma mortality and morbidity.
Low dose ICS reduces symptoms and reduces risk of exacerbatjons and asthma- related hospitalizatjon and death How do cortjcosteroids work in asthma? Barnes PJ, Adcock IM. Ann Intern Med. 2003
2016 update Diagnosis Symptom control & risk factors (including lung function) Inhaler technique & adherence REVIEW RESPONSE Patient preference ASSESS Symptoms T E N M A T R E T S T Exacerbations J U A D Side-effects Asthma medications Patient satisfaction Non-pharmacological strategies Lung function Treat modifiable risk factors STEP 5 STEP 4 STEP 3 Refer for STEP 1 STEP 2 add-on treatment e.g. Med/high tiotropium,* ICS/LABA omalizumab, Low dose mepolizumab* Low dose ICS ICS/LABA** Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium * Add low High dose ICS dose OCS dose ICS Low dose theophylline* Low dose ICS+LTRA + LTRA (or + theoph*) (or + theoph*) As-needed SABA or As-needed short-acting beta 2 -agonist (SABA) low dose ICS/formoterol #
2016 Discontjnuatjon
CONTROLLER MEDICATIONS RELIEVER MEDICATIONS Inhaled cortj tjcosteroids (ICS) (pMDIs or DPIs) beclometasone, budesonide, ciclesonide, fmutjcasone Short-actj tjng inhaled beta2-agonist bronchodilators propionate, fmutjcasone furoate, mometasone, (SABA) (pMDIs, DPIs and solutjon for nebulizatjon or triamcinolone injectjon) salbutamol (albuterol), terbutaline. ICS + long-actj tjng beta2 agonist bronchodilator Short-actj tjng antj tjcholinergics (pMDIs or DPIs) combinatj tjons (ICS/LABA) (pMDIs or DPIs) ipratropium bromide, oxitropium bromide beclometasone/ formoterol, budesonide/formoterol, fmutjcasone furoate/ vilanterol, fmutjcasone propionate/formoterol, fmutjcasone propionate/ salmeterol, and mometasone/formoterol AIT Leukotriene modifj fjers (tablets) montelukast, pranlukast, zafjrlukast, zileuton Long-actj tjng antj tjcholinergic tjotropium Systemic cortj tjcosteroids (tablets, suspension or intramuscular (IM) or intravenous (IV) injectjon) prednisone, prednisolone, methylprednisolone, hydrocortjsone Omalizumb Mepolizumab
“Maintenance and reliever” strategy Humbert et al. Allergy 2008
Beclometasone-formoterol as maintenance and reliever treatment in patj tjents with asthma: a double-blind, randomised controlled trial Papi A et al. Lancet Respir Med 2013 Time to fjrst exacerbatjon + 75 days 36% reductjon in risk The number of days with mild asthma exacerbatjons was also lower with as- needed beclometasone-formoterol than with as-needed salbutamol
Natjonal Review of Asthma Deaths UK 14 % of those who died had been prescribed a single component long actjng beta agonist (LABA) at the tjme of death and at least 3 % were taking a LABA without inhaled cortjcosteroid. UK Eastern Region Confjdentjal Enquiry Seven children had been prescribed non-combinatjon LABAs and of these six were not taking ICS – two children had not been prescribed ICS and four children were not taking their prescribed ICS. Nasser S. Respiratory Research 2016 Anagnostou K et al. Prim Care Respir J 2012
2016
2016 update Diagnosis Symptom control & risk factors (including lung function) Inhaler technique & adherence REVIEW RESPONSE Patient preference ASSESS Symptoms T E N M A T R E T S T Exacerbations J U A D Side-effects Asthma medications Patient satisfaction Non-pharmacological strategies Lung function Treat modifiable risk factors STEP 5 Tiotropium now an add-on STEP 4 optj tjon for adolescents STEP 3 Refer for STEP 1 STEP 2 add-on (age ≥12 years) as well as treatment e.g. Med/high adults, with a history of tiotropium,* ICS/LABA omalizumab, Low dose mepolizumab* exacerbatj tjons Low dose ICS ICS/LABA** Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium * Add low High dose ICS dose OCS dose ICS Low dose theophylline* Low dose ICS+LTRA + LTRA (or + theoph*) (or + theoph*) As-needed SABA or As-needed short-acting beta 2 -agonist (SABA) low dose ICS/formoterol #
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