Dal convegno "Novità diagnostico-terapeutiche in Allergologia e Immunologia Clinica" del 9 Novembre 2019, Torino

1. Università di Torino
Dipartimento di Scienze Mediche
Città della Salute e della Scienza di Torino, Presidio Molinette
Dipartimento Cardiovascolare e Toracico
S.C.U. PNEUMOLOGIA
La patologia pneumologica nella sindrome rinobronchiale
Mauro Mangiapia
AsmAllergie
Novità diagnostico-terapeutiche in Allergologia e
Immunologia Clinica
Torino, 9 settembre 2019

2. Upper and lower airways are considered a unified morphological and functional unit.
More than 2000 years ago, Claudius Galenus studied the upper airway and paranasal sinuses
as integral parts of the respiratory tract, and he assumed that rhinitis and asthma were caused
by secretions dripping from the brain into the nose and lung.
More recently, the concept of united airway disease (UAD) was suggested.

3. The nose plays an important role in the conducting and conditionning of inhaled air, vocal
resonance, olfaction, ventilation and drainage of the sinuses, and protection of the lower
airway.
In addition to their central role in gas exchange, the lungs also have various important
homeostatic functions, including defence mechanisms, lipid metabolism, blood-endothelium
interactions and mediator production.
Although there are some exceptions, the histological characteristics of the normal nasal and
bronchial mucosa are very similar, and both the upper and lower respiratory tracts consist of
common structures such as the ciliary epithelium, basement membrane, loose connective
tissue, glands and goblet cells, which form the basis of the so-called «united airways»

4. Inspired air is conditioned by the nose so that, by the time it reaches the trachea, the air
temperature is about 32°C and the humidity about 98%.
NO produced by the sinuses has a bronchodilatory activity that has been postulated to partially
protect the patency of the lower airway
The main difference between the upper and lower airways is that upper airway patency is
largely influenced by vascular tone, whereas, in the lower airway, airflow is influenced
predominantly by smooth muscle function

5. The UAD hypothesis proposes that any disease process that affects the upper airway is likely
to affect the lower airway, and vice versa, by both direct and indirect means.
It is postulated that rhinitis and asthma represent the manifestations of one syndrome in two
parts of the respiratory tract, the upper and the lower airways, respectively.
➢ At the low end of the severity spectrum, rhinitis may occur alone
➢ In the middle range of the spectrum, rhinitis and airway hyper-responsiveness may be
present
➢ At the high end, rhinitis and asthma may both be present
→ The hypotesis may hold for not only allergic, but also non-allergic presentations.
THE UNITED AIRWAY DISEASE HYPOTHESIS

6. The pathological interactions
between the upper and lower
airways can be divided into:
➢ Air-conditioning
➢ Inflammation
➢ Neural reflexes
UAD: PATHOPHYSIOLOGICAL INTERACTION

7. Ability to clean, warm, and
humidify inhaled air.
Innate and adaptive defense
Patients with AR present
partial or complete loss of
function of the nose
→ bronchoconstriction
→ entrance of allergens and
pathogens
UAD: AIR-CONDITIONING

8. Propagation of inflammation
from the upper airway to lower
airway may occur via
postnasal drip and systemic
circulation
Localized inflammatory
changes leads to a systemic
response, with bone marrow
involvement, resulting in the
release of progenitor cells that
are then recruited to tissue
sites.
UAD: INFLAMMATION

9. Receptors are localized in the
nose, sinuses and pharynx.
The signals are transferred to
the medulla by trigeminal,
facial and glossopharyngeal
nerves.
In the medulla, connections
with vagal nerve cause
bronchoconstriction
UAD: NEURAL REFLEXES

10. ADENOID
HYPERTROPHY
ALLERGIC
RHINITIS
ASTHMA
RHINOSINUSITIS
(with or without nasal polyps)
CONJUNCTIVITIS
OTITIS
SLEEP
DISORDERS
MAIN COMORBIDITIES

11. The link between rhinitis and asthma has been the object of several epidemiological
investigations, which consistently showed an important overlap of the two diseases.
Rhinitis occurs in 75 to 90 percent of adult subjects with allergic asthma and 80 percent of
those with nonallergic asthma.
Conversely, asthma occurs in 25 to 50 percent of individual with rhinitis.
Adults with perennial rhinitis are more likely to have asthma than those without rhinitis.
RHINITIS AND ASTHMA

12. RHINITIS AND ASTHMA

13. Rhinitis (allergic or nonallergic) is correlated with an is a risk factor for the occurence and
severity of asthma
Chronic rhinosinusitis and nasal polyps are also associated with asthma
In particular, patients with late-onset asthma, high periostin levels and eosinophilia often have
CRSwNP. Insufficient control of the upper airways results in insufficient control of asthma and
vice versa.
CRS and NP have both been identified as independent risk factor for frequente exacerbations
in several studies around the world.
RHINITIS AND ASTHMA

14. RHINITIS AND ASTHMA

15. RHINITIS AND ASTHMA: FOCUSING ON STAPHYLOCOCCUS AUREUS
NP and late-onset asthma are mainly
characterised by a Th2 immune
response, which, although mostly
nonallergic, involves increased IgE
levels.
IgE antibodies found in these patients
are predominalty andibodies to S.
Aureus enterotxins, but not inhalant
allergens.
Apart from enterotoxins, known for their
superantigen activity , other secreted
proteins such as serine protease-like
proteins have been identified as
allergens. The secreted proteins are
able to bias the immune response to
type 2 inflammation

16. Respiratory viral infections and potentially
bacterial infection/re-activation precipitate the
vast majority of exacerbations of chronic
respiratory disorders.
The most commonly identified virus (human
rhinovirus) mainly infects the upper
respiratory epithelium causing mild symptoms
associated with the common cold.
hRV can infect bronchial epithelium,
triggering lower respiratory symptoms
INFECTIONS IN THE NOSE AND EXACERBATIONS OF CHRONIC RESPIRATORY
DISORDERS

17. COPD is associated with nasal symptoms,
inflammation and airway narrowing. This is
not recognised in current COPD guidelines.
Symptoms and inflammation are increased at
exacerbation.
Nasal symptoms, which associate with
inflammation, cause impairment of QoL
THE NOSE AND SINUSES IN COPD

18. Upper Airway Cough Syndrome (previously referred to as postnasal drip syndrome) is a syndrome
characterized by chronic cough (i.e. present for ≥8 wks) related to upper airway abnormalities
Key diagnostic factors:
 Cough
 Unpleasant sensation in throat
 Postnasal drip
 Cobblestone mucosa
Other diagnostic factors:
 Nasal abnormalities
 Symptoms of rhinitis
 Posterior pharyngeal mucus
 Wheeze
 Voice disturbance
 Heartburn/indigestion
UPPER AIRWAY COUGH SYNDROME

19.  The upper and lower airways are not only contiguous but also have anatomic and
physiologic similarities
 Postulated mechanisms through which the upper and lower airway may interact include the
nasal bronchial reflex, disturbance of nasal mucosa conditioning, drainage of irritant and
inflamamtor material, and systemic propagation of inflammation
 Patients with chronic or recurrent rhinosinusitis should be evaluated for asthma. Patients
with persistent asthma should be evaluated for shinosinusitis
 Rhinitis (allergic or nonallergic) is correlated with and is a risk factor for the occurrence and
severity of asthma
 Other nasal diseases associated with asthma include acute viral upper respiratory infections,
chronic rhinosinusitis, and nasal polyps
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