Ancora mortj tj per asma: le tante opzioni della terapia - - PowerPoint PPT Presentation

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

• pzioni 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 35th as a cause of death worldwide.

Number of deaths from selected causes Asthma (all ages): 3630 Death rates for selected causes Asthma (all ages): 1.1/100.000 CDC

CDC

Natj tjonal surveillance of asthma: United States, 2001- 2010. 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

• ccur

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

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.

2015

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.

Current smokers 20% Obesity 31%

Respiratory Research 2016

Respiratory Research 2016

Slow onset fatal asthma

Approximately 80 to 85 % of patjents who die of asthma have a history of progressive symptoms for more than 12 hours. eosinophilic infmammatjon and obstructjon

• f airway lumens by tenacious mucus and

desquamated epithelium.

Rapid onset fatal asthma

Up to 20 % death occurs less than 2 to 6 hours afuer symptom onset. severe airway obstructjon mainly due to smooth muscle bronchospasm and neutrophils are the predominant infmammatory cell in the airway mucosa. VS

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.

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

2016 update

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

Asthma medications Non-pharmacological strategies Treat modifiable risk factors Symptoms Exacerbations Side-effects Patient satisfaction Lung function STEP 1 STEP 2 STEP 3 STEP 4 STEP 5

Low dose ICS

Consider low dose ICS Leukotriene receptor antagonists (LTRA) Low dose theophylline* Med/high dose ICS Low dose ICS+LTRA (or + theoph*)

As-needed short-acting beta2-agonist (SABA) As-needed SABA or low dose ICS/formoterol# Low dose ICS/LABA** Med/high ICS/LABA

A D J U S T T R E A T M E N T

Add tiotropium* High dose ICS + LTRA (or + theoph*) Add low dose OCS

Refer for add-on treatment

e.g. tiotropium,*

• malizumab,

mepolizumab*

ASSESS REVIEW RESPONSE

Diagnosis Symptom control & risk factors (including lung function) Inhaler technique & adherence Patient preference

2016 update

2016

Discontjnuatjon

CONTROLLER MEDICATIONS

Inhaled cortj tjcosteroids (ICS) (pMDIs or DPIs) beclometasone, budesonide, ciclesonide, fmutjcasone propionate, fmutjcasone furoate, mometasone, triamcinolone ICS + long-actj tjng beta2 agonist bronchodilator combinatj tjons (ICS/LABA) (pMDIs

• r

DPIs) beclometasone/ formoterol, budesonide/formoterol, fmutjcasone furoate/ vilanterol, fmutjcasone propionate/formoterol, fmutjcasone propionate/ salmeterol, and mometasone/formoterol 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

RELIEVER MEDICATIONS

Short-actj tjng inhaled beta2-agonist bronchodilators (SABA) (pMDIs, DPIs and solutjon for nebulizatjon or injectjon) salbutamol (albuterol), terbutaline. Short-actj tjng antj tjcholinergics (pMDIs

• r

DPIs) ipratropium bromide, oxitropium bromide

AIT

Humbert et al. Allergy 2008

“Maintenance and reliever” strategy

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

Asthma medications Non-pharmacological strategies Treat modifiable risk factors Symptoms Exacerbations Side-effects Patient satisfaction Lung function STEP 1 STEP 2 STEP 3 STEP 4 STEP 5

Low dose ICS

Consider low dose ICS Leukotriene receptor antagonists (LTRA) Low dose theophylline* Med/high dose ICS Low dose ICS+LTRA (or + theoph*)

As-needed short-acting beta2-agonist (SABA) As-needed SABA or low dose ICS/formoterol# Low dose ICS/LABA** Med/high ICS/LABA

A D J U S T T R E A T M E N T

Add tiotropium* High dose ICS + LTRA (or + theoph*) Add low dose OCS

Refer for add-on treatment

e.g. tiotropium,*

• malizumab,

mepolizumab*

ASSESS REVIEW RESPONSE

Diagnosis Symptom control & risk factors (including lung function) Inhaler technique & adherence Patient preference

2016 update Tiotropium now an add-on

• ptj

tjon for adolescents (age ≥12 years) as well as adults, with a history of exacerbatj tjons

In patjents selected for uncontrolled symptoms and persistent airfmow limitatjon despite moderate-high dose ICS and LABA, add-on treatment with the long-actjng muscarinic antagonist bronchodilator, tjotropium, showed improved lung functjon and increased tjme to fjrst exacerbatjon Severe exacerbatjon rate - 21% Time to fjrst exacerbatjon + 56 days Difgerence in FEV1 88±31 ml (P=0.01) and 111±30 ml (P<0.001) Minor changes in symptoms

Tiotropium 5 μg or placebo, both delivered by a sofu-mist inhaler once daily for 48 weeks.

2015

Health behaviour factors were those that related to adherence to asthma management and markers included non-atuendance for appointments in practjces and hospital or self-discharge, poor compliance with asthma medicatjon, and inadequate inhaler technique.

Effective asthma self-management education requires:

• Self-monitoring of symptoms and/or lung function
• Written asthma action plan
• Regular medical review

If PEF or FEV1 <60% best, or not improving after 48 hours

Continue reliever Continue controller Add prednisolone 40–50 mg/day Contact doctor

All patients

Increase reliever Early increase in controller as below Review response

Effective asthma self-management education requires:

• Self-monitoring of symptoms and/or lung function
• Written asthma action plan
• Regular medical review

If PEF or FEV1 <60% best, or not improving after 48 hours

Continue reliever Continue controller Add prednisolone 40–50 mg/day Contact doctor

All patients

Increase reliever Early increase in controller as below Review response

2016 update When combined with self-monitoring and regular medical review, actjon plans are highly efgectjve in reducing asthma mortality and morbidity

Conclusions

Despite major advances in the treatment…asthma stjll kills. Preventable risk factors have been accurately defjned. Identjfying patjents prone to severe exacerbatjons is important because educatjon of the patjent and provision of a detailed actjon plan for these patjents can reduce the risk

• f fatal or near-fatal asthma.

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