03

SEMIOLOGY OF THE RESPIRATORY SYSTEM

TOXICITY AND LUNGS

Group members

Yanelly Díaz - Cristina Llanga - Ramiro Pulgarín - Karla Tarira

Professor: Dr. Ketty Romero
INTRODUCTION
Drug-induced pulmonary toxicity is a diagnosis of exclusion.
This condition can be suspected if the patient has been exposed to a
likely causative drug, develops new signs and symptoms, and has a
remittance of these symptoms once the drug is withheld.

Adverse drug reactions can involve the pulmonary

parenchyma, pleura, airways, pulmonary vascular
system, mediastinum, and neuromuscular system that
contribute to respiration. These reactions can manifest
acutely, subacutely, or chronically. The diagnosis of
drug-mediated pulmonary toxicity is usually
established based on clinical findings. In general,
laboratory analyses are not helpful.
RADIOLOGICAL FINDINGS
Radiologic patterns observed in
drug-induced pulmonary toxicity are highly
variable and depend on the type of
adverse reaction the patient is
experiencing. Most drug-induced
pulmonary toxicities involve the
parenchyma, thus, interstitial infiltrates may
be demonstrated on radiographs. Pleural
fluid may be the only finding. However, the
radiographs may be normal or minimally
abnormal if the airways or pulmonary
vasculature are/is affected.
High-resolution computed tomography
(CT) scanning is more sensitive than
chest radiography for defining the
radiographic abnormalities
 CHEMOTHERAPY AGENTS
● Bleomycin lung toxicity
● Busulfan lung toxicity

PULMONARY FIBROSIS HYPERSENSITIVITY

● Carmustine lung toxicity
DIFFUSE ALVEOLAR DAMAGE
PNEUMONITIS
● Chlorambucil lung toxicity
● Cyclophosphamide toxicity
● Docetaxel induced interstitial
pneumonitis
● Gemcitabine lung toxicity
● Melphalan associated
pulmonary toxicity
● Methotrexate lung disease
● Paclitaxel lung toxicity
● Pemetrexed induced
pneumonitis
CRYPTOGENIC ORGANIZING
PULMONARY HEMORRHAGE
● Thalidomide-induced interstitial
PNEUMONIA
pneumonitis
● Crizotinib associated interstitial
pneumonitis
● Tyrosine kinase inhibitors:
alectinib
● Epidermal growth factor
receptor inhibitors
● Tyrosine kinase inhibitors:
osimertinib
 IMMUNOSUPPRESSIVE AGENTS

ACUTE INTERSTITIAL PNEUMONIA

The mechanisms underlying
lung toxicity vary depending
on the drug but may involve
direct toxicity to lung tissue,
immune-mediated reactions,
or alterations in pulmonary
vasculature.

Sirolimus and Everolimus

Leflunomide

Sulfasalazine

Calcineurin inhibitors
 IMMUNOTHERAPY AGENTS
Pneumonitis is an uncommon but potentially severe or fatal complication of treatment with Immune
checkpoint inhibitors (ICI) therapy. ICI pneumonitis is also more common in patients with lung cancer.
immune-mediated pneumonitis usually happens between 8 to 14 weeks after the start of treatment

Anti-PD-1 PNEUMONITIS
Nivolumab
Pembrolizumab
Cemipilimab
Dostarlimab
Retifanlimab
Toripalimab

Anti-PD-L1
Atezolizumab
Avelumab
Durvalumab

Anti-CTLA-4
Ipilimumab
Tremelimumab

Not all patients are symptomatic and CT may detect

it before any clinical symptoms start to be evident
 MONOCLONAL ANTIBODIES
● Most common pulmonary diseases associated with mAb administration in systemic autoimmune diseases are interstitial
pneumonia and sarcoid-like disorder.
● In these patients, sarcoid-like disease is usually reversible, whereas interstitial pneumonia bears a worse prognosis.
● Before mAb initiation, a careful clinical evaluation of previous pulmonary disease is mandatory, especially in patients with
rheumatoid arthritis.

INTERSTITIAL PNEUMONIA SARCOID-LIKE DISORDER

Biological DMARDs
● Ground glass opacity ● Pulmonary infiltrates
Anti TNF alfa ● Hilar and mediastinal adenopathies
Etanercept
● Fibroatelectatic changes
● Consolidations ● Noncaseating granulomas (nodular areas)
Infliximab
● Air bronchogram
IL-1 antagonist
Anakinra

B lympho depletor
Rituximab

Synthetic DMARDs
Methotrexate
Azathioprine
CARDIOVASCULAR AGENTS
Antiarrhythmics

● Mainly: Amiodarone

● Several forms of pulmonary disease have been

described, including:

○ Interstitial pneumonitis
○ Organizing pneumonia
○ Acute respiratory distress syndrome (ARDS)
○ Diffuse alveolar hemorrhage (DAH)
○ Eosinophilic pneumonia
○ Pulmonary nodules, solitary masses, and also
(rarely) pleural effusion.
CARDIOVASCULAR AGENTS
ACE Inhibitors

● Angiotensin-converting enzyme (ACE)

inhibitors are associated with cough,
angioedema, and pneumonitis

○ Cough: ACE inhibitors can induce a

dry, persistent, and often nocturnal
cough
○ Interstitial pneumonitis: Captopril
and perindopril have rarely been
associated with the development
of diffuse interstitial pneumonitis.
CARDIOVASCULAR AGENTS
Antiplatelet, Anticoagulant and Thrombolytic Drugs

● Use of antiplatelet medications, anticoagulants and

thrombolytic agents has been associated with bland
diffuse alveolar hemorrhage.

● Aspirin: Patients with aspirin-exacerbated respiratory

disease (AERD) can experience acute
bronchoconstriction after ingestion of aspirin. Additional
symptoms may include facial flushing/erythema,
laryngospasm, abdominal cramps, epigastric pain, and
hypotension. Bronchoconstriction is typically reversible.
 CARDIOVASCULAR AGENTS
Beta Blockers
1.280 × 720

● Nonselective β1/β2 blockers (For

example, propranolol) can cause
bronchoconstriction in susceptible
individuals

● This effect is substantially less likely to

occur with selective β1 blockers (eg,
atenolol, metoprolol).
CARDIOVASCULAR AGENTS
Other Drugs

● Drug-induced lupus has been reported with:

○ Beta-blocker medications
○ Hydralazine
○ Procainamide
○ Quinidine

● The diagnosis of drug-induced lupus is based on

the combination of clinical manifestations (eg,
pleuropericarditis), serologic evaluation, and
response to discontinuation of the medication.
 ANTIBIOTIC AGENTS
Nitrofurantoin

● Nitrofurantoin can induce

○ Acute hypersensitivity reaction (1-2 weeks)

○ Chronic pulmonary reaction (occurring after
months to years of exposure)

● Severe lung changes have been described:

○ Nitrofurantoin-induced interstitial
pneumonia (Granulomatous and gian cell) Pneumonia and
pneumonitis patterns
ANTIINFLAMMATORY AGENTS
NSAIDs

● Similar to the aspirin exacerbated pulmonary

disease, some NSAIDs can develop acute
bronchoconstriction after ingestion

Gold

● Also called “Gold lung”, a hypersensitivity

pneumonitis to gold-containing compounds. It
can be distinguished from rheumatoid lung by
its subacute or acute onset, diffuse interstitial
and/or alveolar filling pattern
NON MEDICAL USE DRUGS
● Methylphenidate: Psychostimulant

○ Ritalin lung
○ Panacinar emphysema

● Heroin: Recreative drug

○ Pulmonary edema
○ Pulmonary hemorrhage
○ Eosinophilic pneumonia

● Cocaine: Recreative drug

○ Pulmonary edema
ANTISEIZURE DRUGS
Phenytoin

● Eosinophilic pneumonia comprises a rare and

potentially serious group of lung diseases
characterized by abnormal accumulation of
eosinophils in the lungs.

● Many medications including the anticonvulsant

phenytoin, have been implicated in the
development of eosinophilic pneumonia.
● Methylphenidate: Psychostimulant

○ Ritalin lung
○ Panacinar emphysema

● Heroin: Recreative drug

○ Pulmonary edema
○ Pulmonary hemorrhage
○ Eosinophilic pneumonia

● Cocaine: Recreative drug

○ Pulmonary edema
LARYNX AND PARANASAL SINUSES
LARYNGITIS
Inflammation of the larynx and as with every infection it can be
presented in two forms:
● ACUTE FORM → 3 to 7 days and it is often a self - limiting
condition.
● CHRONIC CONDITION → can last over 3 weeks.

Acute laryngitis is commonly caused by viruses. The diagnosis

is usually obtained by the patient’s history. However, if there’s
an absence of infectious history we should seek for additional
causes and this is going to be named as non infectious
laryngitis.
 The infectious form is more common and it follows an upper
ETIOLOGY respiratory tract infection.

Infectious laryngitis Acute non infectious laryngitis

Bacterial→ Streptococcus pneumoniae, ● Vocal misuse

Haemophilus influenzae, Moraxella catarrhalis ● Gastroesophageal reflux
● Asthma
Viral → Rhinovirus, Respiratory syncytial virus, ● Allergies
Coronavirus, Parainfluenza virus, Adenovirus,
Influenza
Gastroesophageal reflux / laryngopharyngeal
reflux is a common cause of voice symptoms
and laryngitis.
SIGNS & EVALUATION
SYMPTOMS ● History and physical examination.
● Formal voice analysis and fiberoptic
The symptoms are abrupt and worse over 2
laryngoscopy can be used in order to
or 3 days, these can include:
confirm the diagnosis in cases that are
● Dysphonia
refractory to treatment.
● Dysphagia
● It’s important to ask for past medical
● Dry cough and throat pain
history including: immune status,
● Cold or flu symptoms
immunization status, allergy and travel
● Myalgia
history.
● Hoarseness
● Swollen lymph nodes in the neck,
chest, or face.
DIFFERENTIAL TREATMENT
DIAGNOSIS ● Voice rest
● Steam inhalation
● Spasmodic dysphonia
● Medications
● Epiglottitis
○ Bacterial → Antibiotics and
● Reflux laryngitis
corticosteroids
● Chronic allergic laryngitis
○ Viral → Analgesics and
● Neoplasm
mucolytics
● Laryngeal cancer
● Diet modifications
○ Avoidance of irritants
LARYNGEAL CANCER
REPRESENTS ⅓ OF ALL HEAD & NECK CANCERS AND MAYBE A
SIGNIFICANT SOURCE OF MORBIDITY & MORTALITY
● It affects larynx and part of throat which helps to speak,
breath and swallow.
● They are most often diagnosed in patients with significant
smoking history.
● It can involve different subsites of the larynx such as →
supraglottic, glottic and subglottic.
● It is relevant to know that early stage disease is highly curable
with either surgical or radiation monotherapy.
 ETIOLOGY & RISK FACTOR
Smoking is the most significant risk factor for cancers of the larynx, associated with an
estimated 70% to 95% of all cases.
● Smoking ● Advanced age
● Alcohol consumption ● Exposure to paint, asbestos

HISTORY AND PHYSICAL

● Patients are typically male with a history of current or past tobacco
smoking.
● The most crucial component of a physical examination is an invasive
assessment of the primary lesion, including: indirect laryngoscopy,
mirror exam, and often fiberoptic endoscopy.
● We should look for: nodal metastases, weight loss, dysphagia,
aspirations.
SIGNS & EVALUATION
SYMPTOMS 1. Fine needle aspiration if any
suspected nodal disease.
● Sore throat
2. Contrasted - enhanced CT of
● Lump in neck or throat
neck → this allow us to visualize
● Dyspnea
neck lymphatics.
● Dysphonia
3. Esophagogastroduodenoscopy
● Hoarseness
or barium swallow.
● Ear pain
● Cough

CONSIDER: vocal mobility, # of regions

involved, metastatic lesions, involvement of
the: thyroid cartilage, paraglottic and
pre-epiglottic space.
DIFFERENTIAL TREATMENT
DIAGNOSIS ● Radiation therapy
● Chemotherapy
● Acute sialadenitis
● Target therapy
● Bacterial lymphadenopathy
● Surgery
● Benign tumors
● Immunotherapy
● Chronic laryngitis
● Radiosensitizers
● Laryngocele
● Hemangioma
CROUP
Respiratory illness that can affect trachea, larynx and bronchi as a result
it can produce laryngotracheitis, laryngotracheobronchitis and laryngo
tracheo bronchopneumonitis.
● Self-limited illness. If the disease prolongs consider other diagnosis.

ETIOLOGY
● VIRAL AGENTS → Parainfluenza, Respiratory syncytial virus, Adenovirus.
● BACTERIAL AGENTS → Staphylococcus aureus, Streptococcus pneumoniae,
Moraxella catarrhalis.
SIGNS & EVALUATION
SYMPTOMS 1. Quick assessment and initial
management.
Croup is characterized by "seal-like barking"
2. Check vital signs such as: pulse
● Cough
oximetry, airway stability and mental
● Stridor
status.
● Hoarseness
3. Patient stable - history which must
● Difficulty breathing which becomes
include description of onset, duration
worse at night
and progression of symptoms.
● Fever
● Dyspnea PHYSICAL EXAMINATION
● Retractions - nasal flaring, retraction
TO DETERMINE THE SEVERITY
WESTLEY SCORE → 0 TO 17 POINTS
Divided by 5 factors
- Level of consciousness
- Cyanosis
- Stridor
- Air entry
- Retractions
TREATMENT
Depends on the severity based on Westley score
● Dexamethasone
● Nebulized epinephrine + dexamethasone
● Supplemental oxygen
Nasal and vocal cords polyps
 DEFINITION
● The benign inflammatory and hyperplastic outgrowths of the sinonasal mucosa
● Teardrop-shaped growth

ETIOLOGY
● Not entirely clear
Associated with:
● Seasonal allergy
● Asthma
● Chronic sinusitis
● Aspirin-exacerbated respiratory disease
Genetic conditions related:
● Cystic Fibrosis
● Primary ciliary dyskinesia
Frequent nose Breathing through
bleeding mouth Runny nose
 DIAGNOSIS
Suspect in patients with cardinal symptoms
● Progressive nasal obstruction
● Nasal and/or facial congestion
● Rhinorrhea,
● Decreased sense of smell

Inquired about
● Asthma
● NSAIDS

Physical examination
● Anterior rhinoscopy

Imaging Studies
● Computed tomography of the paranasal sinuses
 TREATMENT
The management is determined by the endotypes and
phenotypes of nasal polyps.
Initial Treatment (2-3 months):
● Intranasal corticosteroids and nasal
saline irrigations.
● To clear out the nose and reduce swelling
and polyp size.

Surgery (If initial treatment doesn't work):

- Endoscopic sinus surgery (FESS)
Fix structural issues and improve drainage.
- After surgery, continue with intranasal
steroids and address any allergies you might
have.

Specialized Treatment During Surgery:

- Some patients might get special stents
during surgery that slowly release steroids to
reduce inflammation and prevent polyps
from coming back.
 Advanced Treatment:
for stubborn cases
- Monoclonal antibodies, if nothing else
works. For Underlying Systemic Diseases:
- If your nasal polyps are part of a
Candidates for this therapy have specific bigger condition like cystic fibrosis,
criteria, like severe symptoms or evidence treat the main disease as well.
of a certain type of inflammation.
 VOCAL FOLD POLYPS
Vocal cord lesions, also known as vocal fold lesions, are benign (non-cancerous) growths
called nodules, cysts, or polyps.

hemorrhagic

edematous

They are generally

Unilateral pedunculated

sessile

gelatinous

hyalinized
CAUSE SIGNS & SYMPTOMS
The clinical presentation of benign vocal
Vocal fold polyps are believed to result from fold lesions is most commonly associated
phonotrauma; however, they are also with voice change.
recognized to potentially arise from a single
● Persistent hoarseness
episode of hemorrhage.
● Breathiness
It can also be caused by smoking and/or
● Hoarseness
reflux such as in polypoid corditis (Reinke
● Neck pain
edema).
● Rough or scratchy voice
● Sensation of a lump in the throat
DIAGNOSIS & TREATMENT
Videostroboscopy can be used to detect laryngeal
lesions and characterize them. Both nodules and polyps
may interrupt the vibratory patterns of the vocal fold by
increasing the mass and reducing the pliability of the
overlying cover (ie, cover/body theory of vocal fold
vibration), as well as by impeding proper closure of the
membranous folds throughout the glottic cycle.

Treatment options for VFNs and VFPs include invasive

and noninvasive techniques.
TREATMENT
May initially be treated with voice therapy microlaryngoscopy with excision of the polyps is
performed.

Invasive Techniques
- Microsurgery
- Vocal cord nasal surgery

Noninvasive Techniques
- Voice therapy
- Medical management → medications to treat chronic cough, acid reflux, allergies,
and other medical problems that may contribute to voice disorders.
SINUSITIS
 SINUSITIS
● Sinusitis is an inflammation of paranasal sinuses
● Fifth most common reason for an antibiotic prescription.
● The newer term is rhinosinusitis because purulent sinus disease without similar rhinitis is rare

Classification
● Acute : < 4 weeks
● Subacute: 4 - 12 weeks
● Chronic: > 12 weeks
● Recurrent acute: 4 or more episodes that Paranasal sinus act like echo chambers that amplify voice
lasts at least 7 days in any 1 year period
 ETIOLOGY

Acute Subacute & Chronic

VIRAL
● Infections
● Rhinovirus → Common cold
● Environmental
● Parainfluenza virus → Common cold
● Allergies: dust, pollution
● Influenza virus → The Flu
● Fungi: Aspergillus → usually in
BACTERIAL
immunocompromised patients
● Streptococcus pneumoniae
● Haemophilus influenzae
● Moraxella catarrhalis
● During or after a viral infection
● Blocked sinuses → deviated septum
 Risk factors Signs & symptoms
● Previous cold Major Factors
● Seasonal allergies
● Facial pain/pressure
● Smoking and exposure to secondhand
● Facial congestion/fullness
smoke ● Nasal obstruction
● Structural problems within the sinuses. ● Nasal or post nasal purulence
Eg. nasal polyps ● Hyposmia
● Fever.
● Weak immune system
Minor Factors
(diagnostically significant only with one or
more major factors)

● Headache
● Halitosis
● Fatigue
● Malaise
● Dental pain
● Cough
● Otalgia.
DIAGNOSIS

Waters’ Projection
(X-RAY) Maxillary
sinusitis
 Treatment
● Humidification
● Nasal wash
● Decongestants → pseudoepinephrine, oxymetazoline
○ Caution: in hypertensive patients
● Antihistamines → just in allergic sinusitis
● Topical steroids: allergic sinusitis or chronic sinusitis
● Antibiotics: in case of a suspected infection
○ First line treatment: Amoxicillin or amoxicillin - clavulanate for 10 - 14 days
○ Other antibiotics: Trimethoprim-sulfamethoxazole (High rate of resistance)
○ Resistance cases: switch to a broader spectrum agent:
■ Cefuroxime axetil,
■ Second or third-generation cephalosporins
■ Clindamycin (alone) or + ciprofloxacin
● Chronic sinusitis:
○ Treatment in adults for 5 - 7 days.
○ Children treatment lasts at least 10-14 days.
○ Antibiotics should cover S. aureus.
○ Add metronidazole or clindamycin → if patient hasn’t improved after 5 - 7 days of
treatment. Metronidazole increases anaerobic coverage
 BIBLIOGRAPHY & REFERENCES
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