This document discusses a study of 437 patients with severe asthma (GINA step V) in Italy. The main findings were: - The average annual exacerbation rate was 3.75. - The mean blood eosinophil level was 536.7 cells/mcL and average serum total IgE was 470.3 kU/L. - 64% were on regular oral corticosteroids, 57% with omalizumab and 11.2% with mepolizumab. - The most common comorbidities were rhinitis, nasal polyposis, and bronchiectasis. Bronchiectasis was associated with more frequent severe exacerbations.

1. OLIVIERO ROSSI
oliviero.rossi@unifi.it
S.O.D. IMMUNOALLERGOLOGIA
Direttore Prof.F. Almerigogna
AZIENDA OSPEDALIERA UNIVERSITARIA CAREGGI
FIRENZE
L’asma grave è
sempre «grave» ?

2. Asthma is a heterogeneous condition with
many different phenotypes

3. GINA 2019 ASMA GRAVE : LINEE GUIDA GINA 2019
SEVERE ASTHMA IS ASTHMA THAT IS
UNCONTROLLED DESPITE
ADHERENCE WITH MAXIMAL OPTIMIZED STEP
4 OR STEP 5 THERAPY
Definizione

4. How asthma is classified ?!

5. ASMA SEVERO : FENTITA’ DEL FENOMENO

6. L’asma grave è sempre «grave» ?
A total of 437 patients ,atopics 94.5%, in Global Initiative for
Asthma severity step V) were enrolled into the study.
• annual exacerbation rate was 3.75.
• mean blood eosinophil level was 536.7 cells/mcL
• average serum total IgE was 470.3 kU/L.
• 64% of patients were on regular oral corticosteroid
treatment,
• 57% with omalizumab and 11.2% with mepolizumab.
• Most common comorbidities were rhinitis, nasal polyposis,
and bronchiectasis. Bronchiectasis was associated with more
frequent severe exacerbations
The Severe Asthma Network in Italy: Findings and
Perspectives
Heffler E. J Allergy Clin Immunol Pract. 2019 May - Jun;7(5

7. RIUNIONE SANI
26 GIUGNO 2019
ASMA SEVERO + POLIPOSI = 40,6%
ASMA SEVERO + BRONCHIECTASIE = 30% circa
ASMA SEVERO + POLIPOSI =
RADDOPPIO DEI GIORNI/ANNO DI UTILIZZO
DEI CCS ORALI
CANONICA Et.al. MANUSCRIPT IN PREPARATION

8. La Trahison des images
René Magritte -1929 -

10. NRAD report reveals excessive prescribing of SABAs and
under-prescribing of preventer medication
*Of those patients for which the number of prescriptions was known. Among 189 patients who were on short-acting relievers at the time of death, the
number of prescriptions was known for 165. Among 168 patients on preventer inhalers at the time of death, either as stand-alone or in combination, the
number of prescriptions was known for 128.
NRAD, National Review of Asthma Deaths; SABA, short-acting β2-agonist
Royal College of Physicians. Why Asthma Still Kills? The National Review of Asthma Deaths (NRAD) [online] 2014. Available from:
https://www.rcplondon.ac.uk/projects/outputs/why-asthma-still-kills [Last accessed: December, 2016].
38%of patients on preventer inhalers* received
fewer than
4inhalers in the year leading up to their death…
To comply with recommendations, most
patients would usually need at least
12preventer prescriptions per year
Evidence of under-prescribing
of preventer medication
and 80%received fewer than 12 preventer
inhalers
4%had been prescribed more
than
50reliever inhalers
Evidence of excessive prescribing
of reliever medication
of patients who were on short-acting
relievers at the time of death had been
prescribed more than
39%
12short-acting reliever inhalers In the year
before they died
• The NRAD report was an investigation of recent asthma deaths in the UK by the Royal College of
Physicians

11. MORTALITA’ PER ASMA
• The association between Alternaria sensitization and
asthma mortality is proved in our study and suggests
that asthmatics allergic to this mould have to be
carefully monitored during summer and autumn and
regularly treated.
• A high level of ozone in the environment and the
smoking habit could have had a negative impact on the
fatal attack.
• Once more the inadequate treatment and the lack of
adherence seem to be not only related to the
uncontrolled asthma but also to asthma mortality.
Vianello et al. World Allergy Organization Journal (2016) 9:42

12. Il più alto tasso di mortalità è negli step 1 e 5
0
0,5
1
1,5
2
2,5
3
3,5
GINA Step
Decessi/100pazienti-anno
Mortalità per asma relativa secondo la classificazione per gravità
delle linee guida GINA
1 2 4 53
Step GINA
Grafico elaborato da dati di testo De Vries et al. ERJ 2010; 36: 494–502

13. Admissions to emergency room (ER), overuse of short acting
beta 2 agonists and repeated oral steroid courses to treat
exacerbations are the hallmarks of uncontrolled asthma
The lack of asthma control still represents an unmet need both
in severe as well as in mild asthma
ASMA ED ACCESSI AL PRONTO SOCCORSO

14. Asthma control is poor for many patients at all
levels of severity
• In the MAGIC study of patients with physician-diagnosed asthma (n=1,286), the
incidence of uncontrolled asthma increased with increasing GINA* Steps 2–51
• Asthma control was poor, even at GINA Step 11
1. Olaguibel JM, et al. Respir Res 2012,13:50; 2. Bateman ED, et al. Eur Respir J 2008;31:143–78.
19,5 19,2
12,7
4,0
28,0
37,4 36,2
12,0
52,4
43,4
51,1
84,0
0
10
20
30
40
50
60
70
80
90
Proportionofpatients(%)
Controlled asthma
Partially controlled asthma
Uncontrolled asthma
Asthma control according to GINA-defined*
treatment step (n=624)1
Step 1 Step 2 Steps 3 & 4 Step 5
2006 GINA treatment step2
Reliever As-needed SABA
Controll
er
Low-dose ICS ICS/LABA
ICS/LABA plus
oral GCS or anti-IgE

15. There are still unmet needs in asthma management
that need to be addressed
~50% of patients have poorly controlled asthma2,3
Poor
adherence1
Improper
inhaler
technique1
ICS, inhaled corticosteroid; SABA, short-acting β2-agonist
1. Haughney J et al. Respir Med 2008;102:1681–93; 2. Price D et al. NPJ Prim Care Respir Med 2014;24:14009;
3. Demoly P et al. Eur Respir Rev 2012;21:66–74.
ICS underuse and
SABA overuse1

16. Aderenza al trattamento dell’asma bronchiale

17. Woodcock A, et al. Lancet. 2017;390:2247–2255.
Real life study - 4725 patients enrolled
The Salford Lung Study in Asthma (SLS Asthma), a 12-month, open-label RCT conducted in UK
primary care, compared the effectiveness and safety of initiating fluticasone furoate/vilanterol
(FF/VI) versus continuing usual care (UC) in patients with symptomatic asthma.

18. Randomisation may be:
• 0-30 days after informed consent
• At the same time as informed consent
Existing maintenance therapy, ICS, ICS/LABA
Visit 1:
informed consent
• 4233 patients in primary
care, aged 18+
• GP diagnosis of asthma
• Receiving regular
maintenance treatment:
ICS alone (36%) or
ICS/LABA (64%)
• Symptoms in the week
prior to visit 2
Visit 2:
randomisation (1:1)
assessments
• Routine
respiratory review
• Device instruction
• ACT
FF/VI (100 μg/25 μg or 200 μg/25 μg) once daily
Final visit
assessments
• Routine
respiratory
review
• ACT
• 12 months of normal care
• 3-monthly telephone
(12,24,40)interviews for
safety monitoring
During the 1-year treatment period, patients can have their maintenance treatment adjusted
(stepping-up, stepping-down or switch) at the GP’s/Investigator’s discretion. Patients in the
FF/VI arm could switch to usual care but not vice versa
Salford Lung Study in Asthma

19. Salford Lung Study in Asthma
Baseline characteristics of study partecipants
Adult patients with asthma
were typically older and with
higher body-mass index
20% actively smoking, and a
40% having comorbidities that
would have excluded the majority from many
regulatory RCTs.
the study was open label
• over 90% having daytime or nocturnal
symptoms, or both,
• 36% reporting at least one severe
exacerbation in the year before the
study.

20. Percentage of subjects with either an ACT score of ≥20, or an
increase from baseline of ≥3 at week 24
20
PEA Population: all ITT subjects who have an ACT total score of < 20 at baseline (Day 0), as recorded in the eCRF. (71% of ITT population);
* Responder is defined as an ACT total score ≥ 20 or an increase from baseline of ≥ 3.
ACT: Asthma control test; FF: Fluticasone furoate; PEA: Primary Effectiveness Analysis; VI: Vilanterol
PEA Population
n = 784 n = 977
n = 615 n = 396
In the PEA population, the odds achieving asthma control for subjects who initiated treatment
with FF/VI are twice the odds of achieving asthma control for subjects who continued treatment
with Usual Care; this difference is statistically significant at the 5% level.
Usual Care
(N=1514)
FF/VI
(N=1512)
n
Responder*
Non-Responder
1399
784 (56%)
615 (44%)
1373
977 (71%)
396 (29%)
FF/VI vs. Usual
Care
Adjusted Odds
Ratio
95% CI
P-value
2.00
(1.71, 2.34)
<0.001
NNT = 6.6,
95%
CI (5.4-8.6)
Woodcock A, et al. Lancet. 2017;390:2247–2255.

21. FF/VI consistently enables more patients to improve asthma
control vs. usual care in everyday practice
ACT, Asthma Control Test; CI, confidence interval; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; OR, odds ratio
Woodcock A et al. Lancet 2017; 390:2247–2255.
12 24 40 52
Week
PercentageofresponderswithACTtotalscore
≥20orincreasefrombaseline≥3(%)
Usual care (n=1,514)
80
70
60
40
30
20
10
50
90
OR = 2.04
p <0.0001
OR = 2.00
p <0.0001
OR = 1.77
p <0.0001
OR = 1.83
p <0.0001
FF/VI (n =1,512)
PEA population
at week 52

22. 7,2
6,2
7,88
7,4
8,5
0
2
4
6
8
10
Total study population
(N=4233)
ICS subset
(N=1505)
ICS/LABA subset
(N=2659)
LSmean(SE)numberofsalbutamolinhalers
prescribedperpatientonstudy
FF/VI
UC
Reduced Prescriptions of Salbutamol in Patients on Fluticasone
Furoate/Vilanterol compared with Continuing Usual Care (UC)
Difference FF/VI vs UC (95% CI)
p-value
–0.8 (–1.1, –0.5)
p<0.001
–1.1 (–1.6, –0.7)
p<0.001
–0.6 (–1.0, –0.2)
p=0.001
SE, standard
error
LS mean number of salbutamol inhalers prescribed per patient on study
Grafico elaborato da dati di testo Svedsater H et al ATS Conference 2019; Mm J Respir Crit Care Med 2019;199: A1318
N=2108 N=2116 N=748 N=755 N=1321 N=1322

23. Pazienti in trattamento con FF/VI hanno mostrato una maggiore aderenza al farmaco, misurata
come proportion of days covered (PDC), rispetto a pazienti in trattamento con Bud/Form o FP/Sal
[VAL
UE]
[VAL
UE]
0
0,1
0,2
0,3
0,4
0,5
MeanPDC
FF/VI
n = 1725
BUD/F
n = 1725
FF
/V
I
FF
/V
I
BUD/
F
BUD
/F
Optum Research
Database:
FF/VI vs BUD/F1
0.4
5
0.
35
0
0,1
0,2
0,3
0,4
0,5
p*<0.00
1
FF/VI
n =
3764
BU
D/F
n =
376
4
MeanPDC
IQVIA Real-World
Data:
FF/VI vs BUD/F 2
MeanPDC
0.44
0.34
0
0,1
0,2
0,3
0,4
0,5
FF/VI
n = 3339
FP/SAL
n = 3339
p*<0.001
p*<0.001
IQVIA Real-World
Data:
FF/VI vs FP/Sal 2
FF/VI
n =
3764
BUD/F
n = 3764
Aderenza alla terapia
misurata come proporzione dei giorni coperti (PDC)
BUD, budesonide; FF, fluticasone furoate; F, formoterol; PDC, proportion of
days covered; VI, vilanterol.
1. Stanford H et al The Journal of Allergy and Clinical Immunology: In Practice. 7;5:1488–1496 2019
2. Averell C;Annals of Allergy, Asthma & Immunology;2018;121;S39

24. J Allergy Clin Immunol 2011
Clinical implications: ICS non adherence is a major contributor to
serious asthma exacerbations, and efforts to reduce these events
will likely need to achieve high adherence levels in patients with
uncontrolled asthma.
Steroidi inalatori nell’asma grave
Migliorare l’aderenza

25. Generally, it is believed that between 50 to 75% of
patients with asthma can be considered as having
mild asthma.
Aderenza e strategie terapeutiche
Cosa fare ?!

26. Trattamento asma bronchiale : linee guida Gina 2019

27. GINA 2019
– GINA 2019. Disponibile sul sito: www.ginasthma.org (ultimo accesso: maggio 2019)
Trattamento asma bronchiale : linee guida Gina 2019
Mild asthma

28. I motivi per i quali i pazienti non
assumono con continuità gli ICS
Horne H. Chest 2006; 130: 65s-72s
Studio condotto su 100 pazienti asmatici seguiti dal medico di medicina generale
Steroidi inalatori nell’asma grave
Paura dei farmaci ..Scarsa aderenza al trattamento
Scarsa conoscenza della cronicità della malattia

29. Inhaled Corticosteroids Safety and Adverse Effects in
Patients with Asthma
J Allergy Clin Immunol Pract. 2018 May - Jun;6(3):776-781.

30. Le caratteristiche farmacologiche delle molecole
utilizzate consentono un impiego clinico anche a
bassi dosaggi ,minimizzando il rischio degli effetti
collaterali, in mono somministrazione giornaliera
Le proprietà farmacologiche di Fluticasone furoato e di
vilanterolo sono favorevoli
Fare di più non sempre
significa fare meglio
NON TUTTE LE OPZIONI TERAPEUTICHE PER L’ASMA BRONCHIALE
SONO UGUALI

31. Valotis A et al. Human receptor kinetics and tissue affinity of the enhanced affinity glucocorticoid GW685698X. EAACI
2006
0
500
1000
1500
2000
2500
3000
Relativereceptoraffinity(RRA)
Fluticasone
furoato
Mometasone
furoato
Fluticasone
propionato
Beclometasone
-17-monoprop.
Ciclesonide
Budesonide
Desametasone
FF: affinità per il recettore glucocorticoide
Maggiore è l’affinità di legame al
recettore
Maggiore la «potenza»
antinfiammatoria
FF si lega velocemente al
glucocorticoide umano con una
affinità maggiore di qualsiasi altro
glucocorticoide usato in clinica.
FF si dissocia dal recettore molto
lentamente, fattore che ne consente la
lunga durata d’azione.

32. Valutare effetto antiinfiammatorio attraverso
misurazione del Feno
Bardsleyet al. Respiratory Research (2018) 19:133
FF/VI: durata dell’effetto antiinfiammatorio

33. L’attività massima antinfiammatoria di FF/VI continua per 3
giorni dopo la sospensione del trattamento
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Ossidonitricoesalato,ppb
Giorno
Placebo FF/VI Standard error
Trattamento Post-trattamento
Massimo effetto
anti-inflammatorio
Relvar 92/22 mcg
Bardsley G et al. Resp Res 2018; doi 10.1186/s12931-018-0836-6.

34. Main endpoints: FF/VI 100/25 mcg was associated with a rapid onset of bronchodilation
with an increase in adjusted mean FEV1 change from baseline compared with placebo of
252 mL (95% CI 182e322) after 15 min
The maximum bronchodilation was seen at the 12-h post-dose time point, with an adjusted
mean difference in FEV1 change from baseline of 383 mL (95% CI 285e481
FF/VI: DURATA DELLA BRONCODILATAZIONE

35. Obiettivi del trattamento dell’asma:
controllo attuale vs rischio futuro
Controllo della malattia
Il controllo
attuale
Il “rischio
futuro”
Sintomi
Attività fisica
Uso del farmaco
al bisogno
Funzione
polmonare
Instabilità,
peggiorament
o
Riacutizzazioni
Decadimento
della funzione
polmonare
Comparsa di
effetti avversi
della terapia
Raggiungere Prevenire
Adapted from: Bateman ED J Allergy Clin Immunol. 2010; 125(3):600-8, 608.e1-608.e6.
Raggiungere e mantenere il controllo dei sintomi, e
mantenere livelli normali di attività nella vita
quotidiana attraverso la periodica valutazione dei
sintomi (ACT,ACQ)
e della qualità della vita (AQLQ)
Ridurre al minimo il rischio di morte per asma, di
riacutizzazioni gravi o moderate, di riduzione
progressiva della funzione respiratoria, e di
effetti avversi dovuti alla terapia

36. Obiettivi del trattamento dell’asma:
controllo attuale vs rischio futuro
Controllo della malattia
Il controllo attuale Il “rischio futuro”
Sintomi
Attività fisica
Uso del farmaco al
bisogno
Funzione
polmonare
Instabilità,
peggioramento
Riacutizzazioni
Decadimento della
funzione
polmonare
Comparsa di effetti
avversi della
terapia
Raggiungere Prevenire
Raggiungere e mantenere il controllo dei sintomi, e
mantenere livelli normali di attività nella vita
quotidiana attraverso la periodica valutazione dei
sintomi (ACT,ACQ) e della qualità della vita (AQLQ)
Ridurre al minimo il rischio di morte per asma, di
riacutizzazioni gravi o moderate, di riduzione
progressiva della funzione respiratoria, e di effetti
avversi dovuti alla terapia

37. © Global Initiative for Asthma
Stepwise approach to control asthma symptoms
and reduce risk
GINA 2017, Box 3-5 (1/8)
Symptoms
Exacerbations
Side-effects
Patient satisfaction
Lung function
Other
controller
options
RELIEVER
REMEMBER
TO...
• Provide guided self-management education (self-monitoring + written action plan + regular review)
• Treat modifiable risk factors and comorbidities, e.g. smoking, obesity, anxiety
• Advise about non-pharmacological therapies and strategies, e.g. physical activity, weight loss, avoidance of
sensitizers where appropriate
• Consider stepping up if … uncontrolled symptoms, exacerbations or risks, but check diagnosis, inhaler
technique and adherence first
• Consider adding SLIT in adult HDM-sensitive patients with allergic rhinitis who have exacerbations despite
ICS treatment, provided FEV1 is >70% predicted
• Consider stepping down if … symptoms controlled for 3 months + low risk for exacerbations.
Ceasing ICS is not advised.
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
Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference
Asthma medications
Non-pharmacological strategies
Treat modifiable risk factors
PREFERRED
CONTROLLER
CHOICE
Add tiotropium*
High dose ICS
+ LTRA
(or + theoph*)
Add low dose
OCS
Refer for add-
on treatment
e.g.
tiotropium,*
anti-IgE,
anti-IL5*
SLIT added as
an option
ASMA BRONCHIALE : APPROCCIO TERAPEUTICO IDEALE

38. Primary endpoint
The primary efficacy analysis shows a statistically significant reduced risk for
asthma exacerbations for both treatment doses versus placebo.
Hazard Ratio (% risk reduction > 30%)
12 SQ-HDM: 0.66 (34%), p=0.017
6 SQ-HDM : 0.69 (31%), p=0.028
Placebo
6 SQ-HDM
12 SQ-HDM
Time to first moderate or severe asthma exacerbation
zero days corresponds to the first day
of the ICS reduction/withdrawal period
100 days for placebo 170 days for 6 DU and more than
180 days for 12 DU.
DISEASE MODIFYING EFFECT !!!
Vierchow JC et al., JAMA 2016 1715-1725
50% RIDUCTION ICS 100% RIDUCTION ICS

39. Biologics for Severe Asthma:
oral
inhaled

40. Biologics for Severe Asthma:
Treatment-Specific Effects Are Important in
Choosing a Specific Agent

41. Biologics for Severe Asthma:
Treatment-Specific Effects Are Important in Choosing a Specific Agent

42. Il corticosteroide orale aumenta di
• 5 volte il rischio di fratture e osteoporosi,
• triplica il rischio di malattie a carico dell’apparato digerente
• raddoppia il rischio di diabete, obesità e insufficienza renale
World allergy organization Journal 2019
Spesa gestione effetti collaterali da CS sistemici 243 milioni
Spesa spray antiasmatici (dati Osmed 2017) 138. 5 milioni
Spesa farmaci biologici 50 milioni
Oral Corticosteroids Safety : Adverse Effects in Patients with Asthma

43. L’asma grave è sempre «grave» ?

44. Eur Respir J 2015 Nov;46(5):1262-4.
L’asma grave è sempre «grave» ?

45. Chest 2006
Si generano COMPORTAMENTI SCORRETTI NELLA
GESTIONE…...
L’asma non è il sintomo!
PROGRAMMI EDUCAZIONALI

46. ..Every day, millions of people are
taking medications that will not help
them…
Nature 520, 609–611 (30 April 2015)
«Imprecision medicine»

47. • h 3.00 di notte, vengo chiamato in ps per valutare paziente di 40
anni con lieve dispnea e palpitazioni.
• Nega di prendere farmaci, dice che si sente una lieve tosse dalla
mattina e palpitazioni da qualche ora. E.O. ed esami nella norma,
a parte tachicardia sinusale a 130-140/min
• Cercando di dare un senso a quella tachicardia io e l'infermiere
reinterroghiamo il paziente e gli chiediamo
" per caso ha assunto qualche sostanza oggi?
• Pz "beh si ho preso il Ventolin che usa ogni tanto perché soffro di
asma da allergia ai pollini….
• Infermiere: " ma quando lo ha preso l'ultima volta?"
Pz "e che ne so, oggi l'avrò preso una ventina di volte"
Io (con espressione stupita) "ma grazie al piffero allora"
Pz "e ma non pensavo che fosse un farmaco"
Bisogni insoddisfatti del paziente
con asma bronchiale

48. Asthma control and awareness of asthma
control in INSPIRE
• The majority of patients perceived their asthma control was at least ‘very good’ despite ACQ
findings showing their asthma to be only partly controlled or even uncontrolled
INSPIRE: Quantitative research conducted in 2004/2005 in 11 countries utilising telephone interviews with physician-diagnosed asthma patients on ICS ±
LABA, performed using structured questionnaire.
ACQ, Asthma Control Questionnaire.
Partridge MR, et al. BMC Pulm Med 2006;6:13.
INSPIRE study (n=3,415)
51%
of patients had
uncontrolled asthma, based on
ACQ scores (n=1,732)
55%
of these patients perceived
their asthma control as
‘relatively good’
21%
of patients had
partly controlled asthma,
based on ACQ scores (n=714)
87%
of these patients perceived
their asthma control as
‘relatively good’
28%
of patients had
well-controlled asthma, based
on ACQ scores (n=965)
96%
of these patients perceived
their asthma control as
‘relatively good’

49. La percezione del paziente
L’asma grave è sempre «grave» ?

50. N Engl J Med 2011;365:119-26.
L’asma grave è sempre «grave» ?

51. I pazienti che avevano una forte convinzione che Dio
determinasse il controllo dell'asma avevano meno
probabilità di essere aderenti
CONCLUSIONE:
• La convinzione dei pazienti che la fede in Dio
favorisca un miglior controllo della malattia
contribuisce alla scarsa aderenza al trattamento con
farmaci corticosteroidei per uso inalatorio .

52. Fattori di rischio per un mancato controllo dell’asma bronchiale

53. Ogni quanto dovrebbe essere valutata l’asma?
• 1-3 mesi dopo l’inizio della terapia, dopodiché ogni 3-
12 mesi
• Durante la gravidanza, ogni 4-6 settimane
• Dopo la prima riacutizzazione, entro 1 settimana
GESTIONE INTERDISCIPLINARE DEL PAZIENTE ASMATICO
L’ asma grave è sempre «grave» ?

54. 54
GESTIONE INTERDISCIPLINARE DEL PAZIENTE ASMATICO
Allergologia
Test allergologici in vivo ed in vitro
Eligibilità alla
immunoterapia
allergene specifica
Eligibilità alle nuove
terapie biologiche
Provvedimenti di ordine preventivo ambientale
• Trattare le comobilità : rinite,
poliposi, dermatite atopica, allergie
intolleranze a farmaci ed alimenti ,
immunodeficit
• Impostare diete appropriate
• Vaccinazione anti infettive preventive