Unit 10 Lung Ca/Children/COVID
Cancer of the Lung
Overview of Lung Cancer
Lung cancer is the leading cause of cancer deaths in the US.
Average age at diagnosis: 71 years.
Prevalence in smokers: 10-15% of active smokers develop lung cancer.
Etiology: Cigarette smoking accounts for over 80% of all lung cancer cases.
Tobacco smoke contains approximately 30 carcinogens.
Risk increases with duration of smoking and the number of cigarettes smoked per day.
Familial predisposition linked to cigarette smoking.
Approximately 10-25% of lung cancers occur in never-smokers.
An estimated 25% of lung cancer cases in never-smokers are attributed to passive tobacco smoke exposure.
Industrial hazards linked to lung cancer include asbestos, silica, and radiation exposure.
Histologic Subtypes and Pathogenesis
Lung cancers are predominantly carcinomas:
> 95% of primary respiratory tumors are carcinomas from lung tissue (epithelial lining of bronchi).
The remaining 5% include bronchial carcinoid tumors (neuroendocrine tumors), bronchial gland tumors, lymphomas, and fibrosarcomas.
The lung is a common site for metastasis from other body cancers.
Many inherited genetic mechanisms contribute to lung cancer risk.
Environmental and occupational risk factors include radon gas, asbestos fiber, and diesel exhaust.
Pathogenesis involves carcinogen exposure combined with inherited genetic predisposition leading to tumor development.
Lung cancer is identified as aggressive/non-aggressive, locally invasive/widely metastatic.
Tumor Growth and Paraneoplastic Syndromes
Tumors typically start as small mucosal lesions, following various growth patterns.
All lung cancer types, particularly small cell lung carcinoma (SCLC), can synthesize bioactive products leading to paraneoplastic syndromes:
Paraneoplastic syndromes generally have endocrine, neurologic, and/or immunologic origins.
Caused by ectopic hormonal production by the tumor or autoantibodies responding to the tumor.
Major Categories of Lung Cancer
Lung cancers can be categorized into four major types:
Adenocarcinoma (20-40%)
Originates in bronchiolar or alveolar tissue.
Most common type in North America and in non-smokers, especially assigned-at-birth females.
Weaker association with cigarette smoking than squamous cell carcinoma.
Usually located in peripheral bronchiolar tissue.
May relate to scarring (e.g., old tuberculosis lesions (tubercle).
Poorer stage-to-stage prognosis than squamous cell carcinoma.
Squamous Cell Carcinoma (SCC) (25-40%)
Commonly affects assigned-at-birth males.
Strongly associated with smoking history.
Typically starts in central bronchi as intraluminal growth.
More amenable to early detection via sputum cytologic examination.
Associated with hypercalcemia as a paraneoplastic syndrome.
Small Cell Carcinoma (SCLC) (20-25%)
Characterized by small round to oval cells similar to lymphocytes, growing in clusters.
Highly malignant with early dissemination; rarely resectable.
Common sites for brain metastases, sometimes the first evidence of the tumor.
Associated with paraneoplastic syndromes like:
Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Cushing syndrome from ectopic ACTH production.
Eaton-Lambert syndrome (neuromuscular disorder).
Large Cell Carcinoma (10-15%)
Includes highly anaplastic tumors challenging to categorize as squamous or adenocarcinoma.
Composed of large polygonal cells.
Invades subsegmental bronchi and larger airways.
Poor prognosis due to early distant spread.
Clinical Manifestations of Lung Cancer
Manifestations are categorized into three types:
Symptoms from lung involvement and adjacent structures.
Effects of local spread and metastasis.
Nonmetastatic paraneoplastic effects associated with endocrine, neurologic, and connective tissue function.
Early symptoms are often nonspecific:
Similar to those in chronic bronchitis and smoking-related conditions:
Coughing.
Chest pain.
Excessive sputum production.
Hemoptysis (coughing blood).
Pneumonia.
Airway obstruction.
Pleural effusions.
Weight loss and anorexia may also be noted.
Many lung cancer patients may have metastases visible at the time of presentation.
Common metastasis locations include:
Brain.
Bone.
Liver.
Prior health history considerations:
Recurring bronchitis or pneumonia most common.
Early symptoms: chronic cough, dyspnea, and wheezing from airway irritation and obstruction.
Persistent localized pain worsens upon pleural invasion.
Dull, intermittent, poorly localized retrosternal pain in mediastinal tumors.
Hemoptysis indicates blood vessel erosion by lesions.
Potential clinical signs:
Hard nodes in the neck and/or axillary areas.
Diagnosis of Lung Cancer
Diagnosis relies on:
Detailed history and physical examination complemented by imaging and testing.
Chest radiography and supplementary imaging studies (CT scans, MRI, ultrasound).
Bronchoscopy for direct visualization and percutaneous needle biopsy of lung tissue.
Cytologic studies of sputum or bronchial lavage and scalene lymph node biopsy.
Classifications include:
NSCLCs classified by cell type (squamous cell carcinoma, adenocarcinoma, large cell carcinoma).
Staged via the TNM international staging system.
SCLCs are classified as limited or extensive disease, without TNM staging, as micrometastases are presumed present.
Respiratory Disorders in Children
Most common cause of illness in infancy and childhood
Asthma→ most common peds non-infectious disorder
Pneumo→ huge cause of childhood mortality
Summary of Lung Development
In utero lung development is slower than other systems and often immature at birth,
Leading to morbidity and mortality in preterm infants.
Lung development proceeds through five stages:
Embryonic Period (weeks 4-6 gestation): Formation of rudimentary bronchial structures.
Pseudoglandular Period (weeks 5-16 gestation): Formation of conducting airways resembling glands.
Canalicular Period (weeks 17-27): Major lung structures formed; primitive alveoli begin developing, facilitating respiratory function around week 24.
Type 2 alveolar cells→ surfactant→ develop at 24 weeks
Saccular Period (weeks 27-35): Development of terminal alveolar sacs enhances air exchange and begins to allow survival.
28-30 weeks→ enough surfactant to precent alveolar collapse when breathing begins
Alveolar Period (late fetal through early childhood): Expansion and maturation of alveoli; the capability for respiration is established late in fetal development.
30 weeks→ saccular structures become alveoli
At birth, only a small fraction (1/6 to 1/8) of adult alveoli are present.
Growth of the lung in early years involves an increase in alveoli number rather than size.
Development of Breathing in the Fetus and Neonate
Fetal lungs function as a secretory organ, producing fluids critical for alveolar development.
must be cleared shortly after birth
Irregular fetal breathing movements help condition respiratory muscles without moving fluid in or out of lungs.
At birth, transition occurs from placental dependency to independent respiration:
Rapid expansion of lungs and absorption of lung fluid begins upon first breath.
Highly compliant chest wall facilitates the birthing process and poses subsequent complications in the neonatal period, potentially impairing physiological control of breathing.
Newborns are vulnerable to infections due to immature immune systems.
Respiratory retractions may occur as signs of potential airway obstruction or atelectasis.
Manifestations of Respiratory Disorders in Infants and Children
Respiratory disorders lead to decreased lung compliance or increased airway resistance.
Observable manifestations may include:
Changes in breathing patterns,
Rib cage distortions or retractions,
Audible respiratory sounds,
Accessory muscle usage during respiration.
Children with restrictive lung disorders (pulm edema, RDS) often exhibit:
Rapid shallow breathing and expiratory grunting→ common, increases end-expiratory pressure
Airway obstruction can provoke prolonged inspiratory breath sounds and potential wheezing during exhalation.
Respiratory Disorders in the Neonate
Neonatal respiratory function transitions from placental dependency to air breathing.
Key transition requirements include:
Functioning surfactant system,
Conditioning respiratory muscle integrity,
Establishment of parallel pulmonary and systemic circulations.
Respiratory Distress Syndrome (RDS)
RDS Overview:
Common in premature infants, linked to pulmonary immaturity and surfactant deficiency causing alveolar collapse.
Incidence notably high in infants:
Born at <29 weeks gestation (50-60% incidence).
Risk factors include
Male gender
Birth before 36 weeks
Maternal diabetes
Birth complications.
Etiology and Pathogenesis:
Type II alveolar cells begin surfactant maturation from 25-28 weeks gestation.
Surfactant synthesis is influenced by hormones (insulin inhibits, cortisol promotes).
Labor→ high cortisol for baby→ improved surfactant production
Without adequate surfactant, the alveoli collapse, impairing gas exchange and leading to atelectasis and compromised pulmonary function.
Small underdeveloped alveoli→ difficult to inflate
Chest wall is weak & compliant→ atelectasis (rib cage collapses instead of holding open)
Clinical Manifestations:
Rapid onset of symptoms post-birth within first 24 hours
Tachypnea, expiratory grunting, retractions, nasal flaring, cyanosis.
Progression to hypoxemia and dyspnea→ first 48 hours
Apnea and irregular RR as neonate tires
Chest radiographs show characteristic “ground glass” appearance.
Treatment Approaches:
Administration of exogenous surfactant
Oxygen therapy
Mechanical ventilation.
Mortality Rates:
Decreased due to:
Improved antenatal care→ glucocorticoids >24 birth)
Prevention of asphyxia
Postnatal surfactant therapies.
Bronchopulmonary Dysplasia (BPD)
Overview:
Chronic lung disease stemming from premature birth and treatments, significantly associated with RDS.
High inspired O2 concentrations
Injury from positive-pressure ventilation
Defined by ongoing oxygen dependence after 36 weeks of gestation.
Clinical Features:
Characterized by persistent hypoxemia, chronic respiratory distress, low lung compliance, and high airway resistance
Barrel chest, tachy, rapid/shallow breathing, chest retractions, poor weight gain
Respiratory Infections in Children
→ very common, most are not serious
Infants and young children tend to have more viral infections
immune systems not exposed yet, leads to high amount of infections
Upper Airway Infection
→infection tends to exert its greatest effect during the inspiratory phase of respiration
→ inspiratory stridor is more prominent
Cartilaginous trachea and larynx are poorly developed in infants and small children.
collapses with obstruction→ like when crying→ increases stridor and inspiratory effort
Croup
Common URI in kids
self limiting and benign
2 Types
Viral Croup
Croup (acute laryngotracheobronchitis):
Infection and obstruction of the upper airways
Most common etiology of acute upper respiratory airway obstruction in children
Accompanied by subglottic edema that may be mild to severe
Most common in children three (3) months to five (5) years old
Etiology
most commonly parainfluenza
→ can also be, influenza A virus, respiratory syncytial virus (RSV), rhinovirus, adenovirus, and rubella virus (measles)
Croup pathogenesis: subglottic edema from the infection → upper airway obstruction
→ ↑ resistance to airflow → ↑ intrathoracic negative pressure → upper airway collapse
→ respiratory failure
Common clinical manifestations
High-pitch breath sounds
Barking cough (“seal-like”)→Worse at night
Stridor
Hoarseness
→ needs immediate attention, might lead to resp failure
Spasmodic Croup
Spasmodic or recurrent croup
Etiology unclear: thought to have an allergic origin
Usually affects older children
→sudden onset, usually at night and without viral prodrome
Clinical manifestations: most affected children have a barking cough and viral
symptoms
-Affected children are generally afebrile
usually managed at home; and may not need specific tx
→Presence of stridor (more so at rest), retractions, and/or agitation may suggest a sicker child in need of clinician evaluation and tx
Bacterial Tracheitis
→laryngotracheobronchitis or bacterial croup
Most common life-threatening upper airway infection in children
Generally follows a viral infection
Airway edema and copious purulent secretions → airway obstruction
Clinical Manifestations
May be sudden or preceded by a pre-existing viral upper respiratory tract infection or croup
Acute clinical presentation frequently includes tachypnea, stridor, hoarse voice, fever, cough, and/or ↑ secretions from the mouth and nose
Concurrent infections may be present: sinusitis, otitis, pneumonia, or pharyngitis
Life-threatening emergency requiring immediate clinical attention and tx
Epiglottitis
→Haemophilus influenza type B (Hib) is the most common etiology of acute epiglottitis in children, with infants < 1 year of age being at greatest risk
Incidence has seriously dropped since vaccine advent
Pathogenesis: the epiglottis, rich in blood and lymphatic circulation, arises from the posterior base of the tongue and covers the laryngeal outlet during swallowing
Pathogen invasion of the mucosa with associated inflammation → rapid development of marked edema → severe, life-threatening obstruction of the upper airway
Clinical manifestations:
→In the classical form of the dz, a child between 2 to 6 years of age develops a sudden high fever, severe sore throat, “hot potato” voice, inspiratory stridor, and severe respiratory distress
Classic clinical finding: acute pain and difficulty swallowing (dysphagia)
Child appears acutely ill (pale, toxic, and lethargic) and classically will adopt a forward-leaning position (tripod position) with obvious drooling
Life-threatening emergency requiring immediate clinical attention and tx
Lower Airway Infections
→Lower airway infections → air trapping with prolonged expiration
Wheezing occurs 2⁰ bronchospasms, mucosal inflammation, and edema
Clinical manifestations: child presents with ↑ expiratory effort, ↑ respiratory rate, and wheezing
Severe→ marked intercostal contractions, and signs of impending respiratory failure
Acute Bronchiolitis/Respiratory Syncytial Virus
Common viral-induced lower respiratory tract infection of the small airways
(bronchioles)
children < two (2) years of age →peak incidence, 3-6 months of age
Underlying etiology of respiratory failure in a child affected by acute
bronchiolitis: impaired gas exchange
Distinguishing clinical features: airway inflammation and mucus formation
Most commonly associated pathogen is RSV (respiratory syncytial virus)
→adenovirus, influenza, parainfluenza virus (PIV), and
rhinovirus (in older children)
Peak incidence: winter (late December) with a spike in February
Initial clinical manifestations: significant rhinorrhea followed by a tight cough
(“seal barking”) over several days accompanied by ↓ appetite, lethargy, and fever
Subsequent manifestations:
oVarying degrees of respiratory distress
Severely affected infants appear anxious and distressed 2º dyspnea or
hypoxemia
oAcute bronchiolitis is a major etiology of infant hospital admissions
Dx: nasal swabs are positive for RSV in 70% of suspected cases
Healthy infants generally make a full recovery from bronchiolitis
Bronchiolitis may be linked to asthma later in childhood
Signs of Impending Respiratory Failure
Kids→ respiratory problems originate suddenly, and recovery is usually rapid and complete
Risks:
Epiglottitis → airway obstruction
Bronchiolitis → respiratory failure 2º impaired gas exchange
Clinical manifestations in children with impending respiratory failure due to
airway or lung dz: rapid breathing, nasal flaring, exaggerated use of accessory
muscles, retractions (more pronounced in the child than in the adult because of the more
compliant chest wall), and grunting during expirations
Manifestations of respiratory distress and impending respiratory failure in the
infant and small child:
Severe ↑ in respiratory effort, including severe retractions or grunting; ↓ chest
movement
Tachycardia (heart rate of 150/minute or greater) or advancing bradycardia
Tachypnea (very rapid breathing: 60/minute in newborn to 6 months; or > 30/minute in
children 6 months to 2 years)
Cyanosis not relieved by the administration of oxygen (40%)
Very depressed breathing: ≤ 20 bpm
Retractions of the supraclavicular area, sternum, epigastrium, and intercostal space
Extreme anxiety and agitation
Marked fatigue
COVID-19 Infection
Etiology: SARS-Co-V-2 virus
Individuals at highest risk for adverse sequelae, including death:
> 60 y/o
Those affected by chronic medical conditions, obesity, cancer, and
immunosuppression
Risk factors for children < 17 y/o are similar to those of adults
oMost common risk factors in children: asthma, developmental delays, congenital
cardiovascular dz, and sickle cell dz
Severe COVID-19 dz and mortality: associated with improperly managed chronic
conditions and immunocompromised states
Virus is highly infectious and is transmitted through via droplet or aerosol
Modes of transmission: cough, sneeze, speaking, and/or breathing
Three (3) phases: (1) incubation, (2) symptomatic, and (3) pulmonary
Affected individuals are most contagious during the late period of the incubation
phase (levels of the virus in the body are the highest)
Symptoms emerge 2-14 days after exposure to the virus
In adults, the respiratory system is most commonly affected
oClinical presentation: fever, cough, and dyspnea
In children, clinical manifestations vary widely
oIn many cases, children are asymptomatic or have very mild symptoms
oFever and respiratory symptoms may be absent in children
Early screening and dx: rapid antigen (or rapid diagnostic) tests
COVID-19: Vaccines
Available vaccines deemed safe for most individuals > 18 y/o
Recommended for children > 6 months old or older
After initial vaccination, periodic booster doses are recommended