Le infezioni respiratorie ricorrenti Epidemiologia e diagnosi ... - Sipps

Le infezioni respiratorie ricorrenti
Epidemiologia e diagnosi
Giovanni A. Rossi
U.O. di Pneumologia e Allergologia
I.R.C.C.S. G. Gaslini, Genova
giovannirossi@ospedale-gaslini.ge.it
Istituto
Giannina
Gaslini
Fondazione
Gerolamo
Gaslini

Outline
• Cosa intendiamo per Infezioni Respiratorie Ricorrenti?
• Perché i bambini in età prescolare sono più esposti alle Infezioni
Respiratorie Ricorrenti ?
• Cosa dobbiamo fare di fronte ad un bambino con Infezioni
Respiratorie Ricorrenti ?
La Diagnosi
La Profilassi

Le Infezioni Respiratorie Ricorrenti?
• Con “infezioni respiratorie ricorrenti (IRR)” ci
si riferisce a una serie di episodi acuti a carico
di uno o più settori definiti: il naso, l’orecchio,
il faringe, le tonsille, il laringe, la trachea e i
bronchi
• Questa situazione si manifesta, solitamente, in età prescolare, in
coincidenza della prima socializzazione del bambino con l’ingresso
alla scuola materna
• Benché si tratti di una patologia benigna destinata ad evolvere
favorevolmente verso i 5-9 anni, essa interferisce notevolmente sul
benessere del bambino e della famiglia e determina importanti
costi medico sociali

% rispetto ai livelli negli adulti
100
80
60
40
20
0
-
-
-
-
-
Livelli di Ig seriche nel lattante
Nascita
IgG materne
- -3 0 3 6 9 12 18
Mesi
IgM Bambino
IgG Bambino
IgA Bambino

La dimensione del problema
Il bambino con IRR
• In Italia il 6% dei bambini in età prescolare, presenta IRR nei
primi 2-3 anni di vita
Lancet 2003; 361: 51–59

Gli agenti eziologici
• Gli agenti eziologici responsabili delle IRR siano
identificabili solo occasionalmente, tuttavia
quelli più frequentemente implicati sono i
virus respiratori
• La primitiva infezione virale può essere
complicata da infezioni secondarie, causate sia
da batteri che da virus con la comparsa di otiti
medie, sinusiti ed infezioni broncopolmonari

Viral involved in the pathogenesis of upper
respiratory tract infections
Rhinoviruses 30 - 40%
Coronaviruses 10 – 15%
Influenza viruses 5 -15%
Respiratory syncytial virus 5%
Parainfluenza viruses 5%
Adenoviruses < 5%
Enteroviruses < 5%
Metapneumovirus ? Unknown ?
Unknown 20 – 30%
Heikkinen T. Lancet 2003; 361: 51–59
?
0 20 40 60 80 100
Estimated annual proportion of cases

Rhinovirus
a … “soft” virus”
• Epithelial cell cytotoxicity does not appear to play a major role in the
pathogenesis of Rhinovirus (RV) infection that is characterized by RV-induced
secretion of mediators of inflammation by airway structural/inflammatory cells

Seasonality and etiology of wheezing episodes in
285 children in the 1st year of life
Gern JE. JACI 2006;117:72-8.
RV
RV
RV
RV

Rhinoviruses replicate effectively at
lower airway temperatures
Rhinovirus serotypes 1b, 2, 7, 9, 14, 16, 41, and 70 titrated in Ohio-HeLa
cell cultures at either 33°C or 37°C.
Papadopoulos NG. Journal of Medical Virology 58:100–104 (1999)

Viral infections in relation to age among children
hospitalized for wheezing
Rhino
RSV
Heymann PW. JACI 2004: 114: 239-47.
Rhino
RSV
Rhino
RSV
Rhino
Influenza
Rhinovirus
RSV
Other viruses
Rhino

RV disrupts epithelial tight junctions and promotes
transmigration of NTHi by paracellular route
NTHi
Control
Sajjan U. AJRCCM 2008; 178: 1271–1281
T.J.
Zona occludins (ZO)-1
NTHi
Rhinovirus (RV) 39

Outline
• Cosa intendiamo per Infezioni Respiratorie Ricorrenti?
• Perché i bambini in età prescolare sono più esposti alle Infezioni
Respiratorie Ricorrenti ?
• Cosa dobbiamo fare di fronte ad un bambino con Infezioni
Respiratorie Ricorrenti ?
La Diagnosi
La Profilassi
La Terapia

Major risk factors for RRI in childhood
Host-related
• Low birth weight
• Chronological age
• Genetic factors
• Atopy
• Immunodeficiencies
Immunity
Environment-related
• Day-care attendance
• Having a siblings

Rhinovirus
Allergic children have more numerous
and severe respiratory infections than
non-allergic children
Number of RI/3 months
A. Total RI Number
2.50 -
2.0 -
1.5 -
1.0 -
0.5 -
0.0
1.26
***
0.94
- Atopics Control
Ciprandi G. Pediatr Allergy Immunol 2006: 17: 389–391
Days
B. Total RI Duration
10 -
8 -
6 -
4 -
2 -
8.92
***
4.85
0 -
Atopics Control

I.G.G.
Vicious circle involving viral infection and allergic
sensitization
Viral
infection
Allergic
sensitization

Interaction between atopy and viral
infection at respiratory level
HDM
Increased
epithelial
permeability
Airway
Epithelial
Cell
Rhinovirus
Oddera S. J of Asthma 1998; 35: 401-408.

Atopy and immunological disorders in
218 preschool Italian children with RRI
A. RRI & Atopy
Dellepiane RM. Pediatr Med Chir 2009; 31: 161-4.
-
80 -
60 -
40 -
20 -
Atopic children (%) 100
0 -
50.5
35.3
IRR Control
B. RRI & Immunological
disorders*
-
40 -
30 -
20 -
10 -
Children with ID (n°) 50
39
0 -
IRR
*IgA and IgG2 deficiency
and transient
hypogammaglobulinemia
Rhinovirus

Coexistence of (partial) immune defects in children
(4-14 yrs old) with recurrent respiratory infections
Belgium A. IgA and/or IgG
B. Deficient Ab response to
subclass deficiency
Pneumococcal Polysaccharides
40 -
30 -
20 -
10 -
% of children 50
-
0 -
49%
14%
IRR Control
There was no increase in the prevalence of partial C4 or C2 deficiency, lymphocyte subset
deficiency, or FcRII polymorphism in the IRR patients compared to controls
Bossuyt X. Clinical Chemistry 2007; 53: 124–130
40 -
30 -
20 -
10 -
% of children 50
-
0 -
19%
0
IRR Control

Turkey
IgA and/or IgG subclass deficiency in 225 children
aged 6 months to 6 years with RRI
20 -
15 -
10 -
5 -
% of children 25
IgG subclasses deficiency
-
9%
19%
8%
2%
0 -
IgG3 IgG2 IgG2+IgG3
Ozkan H. J Invest Allergol Clin Immunol 2005; 15: 69-74.

Outline
• Cosa intendiamo per Infezioni Respiratorie Ricorrenti?
• Perché i bambini in età prescolare sono più esposti alle Infezioni
Respiratorie Ricorrenti ?
• Cosa dobbiamo fare di fronte ad un bambino con Infezioni
Respiratorie Ricorrenti ?
La Diagnosi
La Profilassi
La Terapia

Diagnosis
• Careful Medical History and Clinical Examination
are usually sufficient to make a diagnosis of RRI
and no further examinations are generally
needed in the majority of the cases
• A complete Blood Count with differential is sufficient to
exclude neutropenia, while the evaluation of Antibodies
against Recall Antigens rules out T-lymphocyte defects
• Total Immunoglobulin Levels are also important to evaluate
the presence of a selective IgG or IgA deficiency but
more severe cases may need further evaluation

Low proportion of children with recurrent RRI have
detectable amounts of antigen-specific salivary sIgA
• Staphylococcus aureus
• Streptococcus pyogenes
• Klebsiella pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
• Streptococcus pneumoniae
Rossi GA. Immunol Letters 2003; 86: 85-91.
sIgA
0 5 10 15 20 25 30 40
% of children

A 13 years old girl with 2nd episode of
pneumonia of the right lower lobe

Angio-TAC con ricostruzione 3D
Pulmonary sequestration

A.
Sacco O. Ped Pulmonol 2009; 44:244–248
Recurrent LRTI in a 5-yr-old girl
B.
C.

Reassure parents and give simple advises
• An accurate environmental prophylaxis
• Reducing environmental tobacco smoke at home
• The postponed enrolment of children at day-care centers
reduces the risk of RI
• Optimal day-care center selection, when possible:
Only a limited number of children
Large rooms with a good ventilation
Located in modern buildings in areas with less air pollution
With professionally trained staff
De Martino M. PAI 2007: 18 (Suppl. 18): 13–18.

Prophylaxis-treatment
• Prophylactic treatment with antibiotics is
neither indicated nor useful
• Adenoidectomy and tonsillectomy should
be planned only in conditions included in
validated guidelines
• The role of biological response
modifiers (BRM) claimed to
improve immunity in RRI children is
still uncertain ……. As we will
discuss later…..
De Martino M. PAI 2007: 18: 13–18.

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