1. UPPER AIRWAY COUGH SYNDROME
Berna USLU COŞKUN
SBU SİSLİ HAMİDİYE ETFAL E. A. HOSPITAL ENT DEPARTMENT
ISTANBUL/TURKEY

2. Upper airway cough syndrome was coined to encompass diseases affecting upper airways, like rhinitis and sinusitis, which results in chronic cough

3. Types of cough Acute: Less than 3 weeks Subacute: 3-8 weeks
Chronic: More than 8 weeks

4. Common causes of chronic cough
Asthma
Gastro Esophageal Reflux Disease
Upper Airway Cough Syndrome

5. Causes of chronic cough
Postinfectious
Medications (ACE inhib)
Airway diseases and parenchymal diseases

6. UACS vs PNDS
Postnasal drip syndrome
UACS

7. UACS vs PNDS
USA UK
American chest physicians adopted PNDS as the most common cause of chronic cough
In 2006 ; in patients with chronic cough related to upper airway abnormalities the committee considers the term UACS to be more accurate and used instead PNDS
British used the term ‘rhinosinusitis’ instead of PNDS
A relationship between PNDS and chronic cough was not accepted by UK chest physicians
They prefer to use ‘rhinosinusitis’ instead of PNDS

8. ERS
The European Respiratory Society characterizes postnasal drip as a symptom rather than a disease
The most patients with postnasal drip do not cough
Based on that postnasal drip cannot fully explain the cause of a cough, and does not accept the diagnosis PNDS/UACS

9. ERS
PNDS/UACS is described as “rhinitis/rhinosinusitis” or “upper airway diseases caused cough”
Such diseases account for 6-21% of chronic cough cases

10. Pathogenesis
It is still unclear but there are some theories described

11. Pathogenesis Postnasal drip theory Airway inflammation
Sensory neural hypersensitivity theory

12. Postnasal drip syndrome
PNDS is the drainage of secretions from the nose or paranasal sinuses into the pharynx
Clinically, the diagnosis of PNDS largely rests on the reporting of the patient of this sensation of having something drip down into the throat, nasal discharge, or throat clearing
The presence on examination of the nasopharynx and oropharynx of mucoid or mucopurulent secretions or cobble stone mucosa also is suggestive

13. Postnasal drip theory
Bardin et al placed radionuclide in the maxillary sinus of sinusitis patients and 24 hours later detected its presence in maxillary sinus, nasopharynx, esophagus and lower GIT; however, its presence was not detected in the pulmonary aspirate
This study showed that after 24 hours secretions of the nasal and sinuses had barely entered the lower airways

14. Postnasal drip theory
O’Hara and Jones followed up 108 consecutive rhinitis/rhinosinusitis patients who displayed symptoms of postnasal drip and found that only 21% complained of cough
Among the patients with a cough only 8% had postnasal drip and a cough
These data indicate that cough is uncommon in patients with postnasal drip and may not be associated with postnasal drip

15. Airway inflammation theory
Upper airway
Lower airway

16. Lower airway inflammation
It is commonly associated with chronic cough
Histamin, prostaglandin can increase the sensibility of cough via stimulating local nerve endings in the lower airways

17. Lower airway inflammation
Niimi reported that patients with UACS showed a remodelling of the airways, characterized increased sub-basement membrane thickness, vascularity, vessel size and signs of goblet hyperplasia
The submucosal infiltration of mast cells in patients with nonasthmatic cough differed from the infiltration of eosinophils and neutrophils found in patients with asthmatic chronic cough

18. Airway inflammation which might be associated with activation of mast cells, could be a cause of increased cough sensitivity, leading to cough

19. Upper airway inflammation
Some ORL have proposed that UACS is not only associated with nasal diseases, but might also influenced by a chronic inflammation in the pharynx and larynx, such as inflammations resulting from allergic pharyngitis and chronic tonsillitis
Such inflammations may result long term contact with nasal and sinus secretions

20. Upper airway inflammation
Chronic tonsil hypertrophy in child and adult may be associated with cough, that could be relieved after tonsillectomy

21. Sensory neural hypersensitivity theory
İncreased neural sensitivity in the pharynx or larynx
Activated nasal nerves and increased cough sensitivity
Cough hypersensitivity syndrome

22. Activated nasal nerves and increased cough sensitivity
Pecova reported increased cough sensitivity in AR patients
Histamin is an important mediator and directly stimulated sensory neurons
Capsaicin activates local nerves via combining with TRPV1 in nerve endings
Histamin and capsaicin don’t produce cough they just increase cough sensitivity

23. The mechanism of nasal neural activation elicited increased cough sensitivity is not clear
After accepting external stimulus the nasal mucosa produces a variety of inflammatory factors such as histamin
This increases cough sensitivity

24. Increased neural sensitivity in the pharynx or larynx
Bucca, proposed the concept of larynx hyper-resposiveness (LHR)
This is a protective reflex-laryngeal chemical reflex can prevent a liquid substance from entering the lower airways
LHR was found in 76% in UACS patients
These patients seemed to have increased sensitivity in the pharynx and larynx, which made it easier to generate cough after providing a stimulus

25. Cough hypersensitivity syndrome
Patients with CHS usually present with one of three different phenotypes
1- Patients with rhinal symptoms
2- Patients with Th-2 cell dominant phenotype
3- Patients with reflux

26. It has been demonstrated that the pathological change associated with both sensory hyper-reactivity and cough hypersensitivity is the upregulation of TRPV1 expression in sensory nerves
TRPV1 antagonists are effective for improving the symptoms

27. Mechanisms influencing cough reflex in subjects with upper airway disease
Complete nasal obstruction and lack of nasal functions in oral breathing
İnhalation of cold dry and unfiltered air
Damage of the superficial mucosal layers with increased penetration of tussigenic factors to the nerves
Neurogenic and immune factors iniated inflammation
Overproduction of mucus and post nasal drip
Activation of mechanosensitive fibers in pharynx and larynx
Activation of chemosensitive C fibers by mediators
İncomplete nasal obstruction and nasal breathing with increased resistance
Formation of secretions and inflammatory mediators, cells and their products-microaspiration to the lower airways
Activation of chemosensitive C fibers
Nasobronchial reflex
Modulation of activity of airway afferents by increased tone of the smooth muscle cells
İrritation of nasal trigeminal afferents by inflammation
Effects trigeminal-vagal drive and up-regulation of cough pattern generator activity
Virus induced changes
Increased expression of TRPV1

28. How to diagnose PNDS There is no objective test for it
No way to quantify the amount
No way to directly prove that it is causing cough

29. Clinical features No pathogonomic finding
Chronic cough with or without expectoration
Throat cleaning
Nasal discharge
Sensation of secretions dripping down the throat

30. What we see? Presence of secretions in posterior pharyngeal wall
Cobble stone appearance of pharyngeal wall mucosa

31. Conditions associated with UACS
Rhinitis
AR-NonAR
Vasomotor rhinitis-Postinfec rhinitis
R. medicamentosa, R of pregnancy-Occupational R
Sinusitis
Bacterial sinusitis
Allergic fungal sinusitis

32. Treatment
Difficult
If there is a spesific cause: Treatment should be directly to that
But many times we can not find it
Empiric therapy initiated

33. Empiric therapy First generation antihistamines and decongestants
First generation antihistamines with their anticholinergic action they have effect on cough
Second generation antihistamines have a role through reduction of nasal congestion (When AR is the causative agent in UACS)

34. Empiric treatment
Good
Partial No
Response

35. Good: Continue treatment
Partial: Continue treatment and further investigate (Sinus imaging and prolonged ab)
Bad: Search for other causes; undergo sinus imaging

36. ACCP(American College of Chest Physicians)
Recommendation 1: In patients with chronic cough related to upper airway abnormalities, the committee considers the term UACS to be more accurate and therefore it should be used instead of PNDS

37. ACCP
Recommendation 2 : In patients with chronic cough, the diagnosis of UACS-induced cough should be determined by considering a combination criteria, including symptoms, physical examination findings, radiographic findings and ultimately the response to spesific therapy. Because it is a syndrome, no pathognomic findings exist.

38. ACCP
Recommedation 3: In patients in whom the cause of the UACS-induced cough is apparent, spesific therapy directed at this condition should be instituted.

39. ACCP
Recommendation 4: For patients with chronic cough, an empiric trial therapy for UACS should be administered because the improvement or resolution of cough in response to spesific treatment is the pivotal factor in confirming the diagnosis of UACS as a cause of cough

40. ACCP
RECOMMENDATION 5: A patient suspected of having UACS induced cough who does not respond to empiric A/D therapy should undergo sinus imaging

41. ACCP
RECOMMENDATION 6: In patients whom a spesific etiology of chronic cough is not apparent, empiric therapy for UACS in the form of a first generation A/D preparation should be prescribed before beginning an extensive diagnostic workup

42. THANK YOU