ENT, CRSwNP, AERD and NSAID reactions Flashcards
What is AERD?
- Aspirin-exacerbated respiratory disease (AERD), also known as Samter’s Triad
- Three clinical features:
» 1) Asthma
» 2) Sinus disease with recurrent nasal polyps
» 3) Sensitivity to aspirin and other NSAIDs that inhibit COX-1.\ - Sinus disease: nasal congestion, polyps, chronic sinus infections, loss of small; symptoms often don’t respond to conventional therapy
- Sensitivity to NSAIDS: classically involve upper respiratory (increased nasal congestion, frontal headache or sinus pain, and sneezing) and lower respiratory (cough, wheezing, chest tightness), but they can also induce skin flushing, rash, abdominal pain and occasionally vomiting.
- ~9% of all adults with asthma and 30% of patients with asthma and nasal polyps have AERD.
- Pts with AERD have large numbers of eosinophils in their nasal polyps and often have elevated levels of eosinophils in their blood
Treatment of AERD
- Avoid all NSAIDs to prevent reactions
- Inhaled corticosteroids for asthma
- Intranasal corticosteroids and saline rinses for nasal symptoms and polyps
- Surgical removal of nasal polyps (recurrence of polyps is high)
- Aspirin desensitization to initial daily high dose aspirin therapy
» reduce need for corticosteroid medications
» can decrease regrowth of nasal polyps - Biologics
Definition of CRSwNP
2 or more of the following symptoms lasting at least 8-12w (PODS):
> > Facial congestion/fullness (P)
Facial pain/pressure/fullness (P)
Nasal obstruction/blockage (O)
Purulent anterior/posterior nasal drainage (D)
Hyposmia/anosmia (S)
How to score impact of CRSwNP?
- The 22-item Sinonasal Outcome Test (SNOT-22) is a PROM designed to evaluate the impact of chronic rhinosinusitis (CRS) on HRQoL
- Captures symptom severity, social and emotional impact, productivity, and sleep consequences of CRS. Items are scored from 0 (no problem) to 5 (problem as bad as it can be) and summed to form a total score of 0 to 110.11
- Patient-reported outcome measures (PROMs)
Biologics approved for CRSwNP
- Biologics approved for treatment of CRSwNP in United States and Europe: dupilumab, omalizumab, and mepolizumab
- No completed head-to-head studies comparing these agents for treatment of CRSwNP. However, dupilumab was consistently found to be the most effective in multiple systematic reviews and indirect comparisons.
What is pathogenesis of CRSwNP?
Type 2 inflammatory pathway:
IL4, IL5, IL13
IL5R
IL33
IgE
What factor is most important in the symptom of nasal congestion?
Activation of innervation of nasal mucosa
The symptom of nasal congestion is primarily due to the interaction between airflow in the nasal passages and airflow receptors in the nasal mucosa.
There are multiple factors that affect nasal airflow, which include inflammatory and non-inflammatory causes.
Studies have shown that patient perception of congestion does not correlate with actual compromise in nasal airflow.
What is the next best test if a patient presents with unilateral, clear rhinorrhea after trauma or surgery?
Concern for a CSF leak
Next best test would be beta-2 transferrin of the fluid
Traditional **chemical analyses **such as glucose, protein, or specific gravity, are unreliable for confirmation of CSF fluid. Blood in nasal discharge can lead to false positive glucose test. Radiographic studies, esp with injection of dyes or radiographic compounds, are costly and may introduce additional risks to patient.
What are common triggers of NAR (non-allergic rhinitis)?
- Changes in the environment (dry cold air, humidity, barometric pressure)
- Airborne irritants including odors and fumes (cologne, perfume, cleaning products, cigarette smoke, diesel and car exhaust)
- Certain medications (b-blockers, aspirin, and other NSAIDs)
- Dietary factors (spicy food, alcohol)
- Sexual arousal, exercise, strong emotions or stress, and hormone levels.
Treatment of NAR (non-allergic rhinitis)
Pure NAR does NOT seem to be as responsive to 2nd gen H1-antagonists, INCS, leukotriene-modifying agents, or allergen IT
Responds better to:
- Topical nasal antihistamines
- Combo nasal corticosteroids and nasal antihistamines
- Nasal saline rinses
- Oral first-generation H1-antagonists (b/c of anticholinergic effect) at bedtime to minimize sedating side effects
- Ipratroprium bromide nasal spray, especially if chief complaint is rhinorrhea (in gustatory rhinitis: ipratroprium bromide 0.03% nasal spray 1-2 puffs each nostril before each meal)
Why recommend aspirin desensitization and therapy in AERD?
Multiple studies have shown that desensitization and daily treatment with aspirin can significantly improve overall symptoms and quality of life, decrease formation of nasal polyps and sinus infections, reduce the need for oral corticosteroids and sinus surgery and improve nasal and asthma scoresin patient with AERD at both 6 months and after one year of therapy (P<0.0001)
dx of ABRS
ABRS symptoms classified as major and minor (Table 2). Minor symptoms may be clinically helpful, but are not used for dx of ABRS.
algorithm for diagnosis and treatment of ABRS
Premedication for oral aspirin challenge?
- Patients with AERD have a high degree of leukotriene overproduction
- Not already taking leukotriene-modifying drug (LTMD)= pretreat with one prior to undergoing oral challenge or desensitization to NSAIDs
- Already taking LTMD= continue through desensitization
- LTMDs significantly impact results of oral NSAID challenge by blunting bronchospastic component
- LTMDs attenuate the severity of reactions during desensitization
FESS
- Functional endoscopic sinus surgery (FESS)
- Management of chronic rhinosinusitis
- Poor prognosis after FESS: age, history of AR, severity of dysosmia, history of nasosinusitis surgery, and long-term use of nasal decongestant
- Protective factor: Medical management after surgery
- Most common minor complication post-FESS is epistaxis
- Major complications (relatively low rate): Skull base injury (including CSF fluid leak), orbital injury , and hemorrhagic sequelae
- Factors that increase risk of major complications: age over 40 years, surgery involving the frontal sinus, sphenoid sinus, or all sinuses, use of image guidance systems during surgery, primary payer of Medicaid.
COX-1 vs. COX-2
- COX-1 expressed constitutively in all human cell types and involved in protective physiologic functions
- COX-2 is inducible enzyme expressed in inflammatory cells in presence of appropriate stimuli
- COX-2 mediates generation of same range of prostaglandins as COX-1, but only at sites of inflammation
- COX-2 inhibition largely responsible for desired anti-inflammatory effects of NSAIDs
COX-2 selective NSAIDs
Celecoxib
Pseudoallergic reactions: Types
Nonimmunologic reactions that are related to COX-1-inhibiting properties of drug
Anterior rhinoscopy
The sphenoid sinus (green) is the most posterior sinus that is contained in the sphenoid bone. The ostium of the sphenoid sinus lies medially in the anterosuperior portion of the anterior sinus wall.
The ethmoid sinuses or ethmoid air cells (blue) are located in the ethmoid bone and have variable size and number among individuals. They are divided into the anterior group, which drains into the superior meatus and the posterior group, which drains into the middle meatus. The basal lamella divides the anterior and posterior ethmoid cells.
The frontal sinus is not present at birth but develops during childhood in the frontal bone. Each frontal sinus drains into the middle meatus of the nose via the infundibulum.
The maxillary sinuses are the largest sinuses that are located in the body of the maxilla, bounded by the floor of the orbit, zygomatic process of the maxilla, lateral wall of the nose, and the alveolar process. The maxillary sinus drains into the middle meatus through the osteomeatal complex.
- A 27-year-old woman from Georgia with AR
- Increasing nasal congestion that has slowly worsened over the past 5m
- OTS allergy pills have “stopped working”
- Otherwise healthy
- Vital signs are stable without fever. Mild pain upon palpation of cheeks.
Her CT of the sinus is shown:
Allergic fungal rhinosinusitis (AFRS)
- Specific type of chronic rhinosinusitis (CRS)
- Noninvasive hypersensitivity reaction to fungi
- Young and immunocompetent and show evidence of allergy to one or more fungi
- CT scan demonstrates the characteristic dense opacification of bilateral ethmoid and maxillary sinuses, inspissated secretions, and polypoid tissue
Diagnostic criteria and management for AFRS
- Definitive diagnosis usually confirmed after sinus surgery
- Surgical treatment with endoscopic sinus surgery (ESS): removal of polyps, inflammatory mucin, and fungal debris + reversal of bony expansion into the orbit and brain
- Medical management consists of systemic and topical glucocorticoids. Oral corticosteroids for perioperative care- help reduce inflammation and improve surgical field
Factors affecting nasal airflow
Nasal vasculature, particularly the nasal venous sinuses, are exquisitely sensitive to sympathomimetic hormones and medications. The nasal venous sinuses have α-1 and α-2 surface receptors that modulate blood flow and, in return, nasal airway resistance and nasal airflow.
Mediators released in AR
(nasal provocation challenge in AR)
EPR- early phase response
LPR- late phase response
Position of sinuses
The ethmoid bulla, also known as bulla ethmoidalis, is the largest and most consistent air cell of the anterior ethmoid air cells. It is a component of the ostiomeatal complex
concha bullosa
