Ch 36- ALT of pulmo fxn in children

• Infants and children have smaller airways than adults, leading to greater obstruction from mucosal edema or secretion.
• Younger children have proportionately larger tonsils, adenoids, and epiglottis, increasing obstruction risk with swelling.
• Infants up to 3 months are obligate nose breathers, making nasal congestion a serious threat, especially during sleep.

Cystic Fibrosis (CF) Overview

• CF is an autosomal recessive inherited disease affecting the lungs, pancreas, and digestive system.
• Caused by defective chloride ion transport due to mutations in the CFTR gene.
• CFTR protein regulates salt and fluid flow in and out of cells.
• CFTR protein is an activated chloride channel present on epithelial cells lining airways, bile ducts, pancreas, sweat ducts, paranasal sinuses, and vas deferens.
• Mutations in the CFTR gene cause CFTR protein malfunction or absence -> buildup of thick mucus -> persistent lung infection, pancreatic destruction, and complications.

Etiology of CF

• CF results from mutations in the CFTR gene on chromosome 7.
• There are over 2,000 different CFTR mutations, grouped into 6 classes.
• Classes 1-3 are more severe, while classes 4-6 are milder, generally pancreatic sufficient.
• CF severity correlates with the gene class.
• CF is more common in white individuals, with approximately 28,680 cases in the U.S. and 70,000 worldwide.
• Mortality is related to CF class, with treatment directed at specific gene classes.
• The median age of CF diagnosis is 4 months; more than half of the CF population is 18 years or older.
• The median predicted age at death for CF patients is 30.1 years.

Inheritance Pattern of CF

• Both parents must carry a mutated CFTR gene for a child to have CF.
• Carriers have one normal and one mutated gene but show no symptoms.
• When both parents are carriers the child has a 25% chance of having CF, a 50% chance of being a carrier, and a 25% chance of neither having CF nor being a carrier.
• If one parent has CF and the other is a CF carrier, there is a 50% chance the child will have CF and a 50% chance the child will be a carrier.
• CF carriers do not have the disease but can pass the defective gene to their children; approximately 10 million people in the U.S. are carriers.
• Autosomal recessive inheritance is a key concept to remember in the context of CF.
• F508delCFTR is the most common CF mutation.
• Mortality is higher in severe gene classes (1-3) compared to milder classes (4-6).

Teaching of CF

• Nutritional guidelines and counseling are a necessary care component for individuals with CF

Clinical Manifestations of CF

• CF affects the lungs, pancreas, and digestive system.
• Respiratory and GI systems are most commonly involved.
• Overall severity of CF is highly variable.
• Affected siblings may have disparate courses and different clinical phenotypes, despite identical CFTR mutations, environment, and treatment strategy.
• CFTR genotype is expressed differently in epithelial cells of different organs, influencing phenotypic variation in clinical manifestations and disease progression.
• Respiratory symptoms include persistent cough, excessive sputum production, wheezing, chronic pneumonia, digital clubbing (early sign), and barrel chest or persistent crackles (late sign).
• Digestive symptoms include poor growth due to nutrient malabsorption and steatorrhea (fatty stools) due to pancreatic insufficiency.

Diagnosis of CF

• Newborn screening for CF is universal in the United States, using the Immunoreactive trypsinogen (IRT) blood test.
• Sweat chloride test (sweat chloride >60 mEq/L is diagnostic).
• Genetic testing for CFTR mutations.
• A history of CF in a sibling or a positive newborn screen may lead to CF diagnosis

Pathophysiology of CF

• CF involves multi-organ disease affecting the airways, digestive tract, and reproductive organs.
• In the lungs, defective chloride transport leads to thick, sticky mucus, blocking airways, causing infection, and inflammation.
• Common lung infections are caused by Pseudomonas aeruginosa and Staphylococcus aureus.
• Buildup of mucus is difficult to clear, leading to chronic inflammation and structural damage like bronchiectasis (airway dilation).
• CF leads to pancreatic insufficiency due to mucus plugging in the ducts, impairing nutrient absorption. Patients need pancreatic enzyme replacements to digest food properly.
• CFTR variants are grouped into 6 classes, with the most common mutation being F508delCFTR.

Complications of CF

• Chronic respiratory infections and bronchiectasis
• Pulmonary vascular remodeling (due to localized hypoxia and arteriolar vasoconstriction) results in pulmonary hypertension and cor pulmonale.
• Respiratory failure is commonly the cause of death in CF patients
• Hemoptysis (LIFE-THREATENING; due to inflammation associated with bronchiectasis and enlarged bronchial arteries)
• Development of peripheral bullae (due to airway obstruction and weakening of airway wall) may lead to Pneumothorax
• Microabscess formation, and patchy consolidation, which can lead to Pneumonia
• Peribronchial fibrosis and Cyst formation

Treatment of CF

• Primary focus of treatment is pulmonary health and nutrition.
• Pulmonary care includes chest physiotherapy (CPT), high-frequency chest wall oscillation, and PEP devices to help clear mucus.
• Aerosol therapy involves bronchodilators, dornase alfa(to break down mucus, and hypertonic saline (liquifies mucus)
• Antibiotics (oral, inhaled, intravenous) are used to treat different pathogens (e.g. Pseudomonas aeruginosa, S. aureus, Burkholderia cepacis nontuberculous mycobacteria)
• Azithromycin, ibuprofen, and corticosteroids reduce airway inflammation and improve lung function.
• CFTR modulators: Ivacaftor and Lumacaftor-ivacaftor help correct CFTR protein function.
• Oral antibiotics and anti-inflammatory drugs.
• Ivacaftor - approved in U.S., Canada, Australia, and European Union; ages 2 years and older; used for G551D CFTR gating mutation
• Lumacaftor-ivacaftor (corrector-potentiator combo drug) – approved in U.S.; ages 12 years and older; must be homozygous for the CFTR mutation F508del (34% of the U.S. CF population)
• Drugs are effective in → lung, GI tract, and sweat glands
• VERY EXPENSIVE
• Recombinant human growth hormone → shown to improve lung function, height, and weight in children with severe CF
• Lung transplantation may be needed in severe cases. Nutritional care: High-calorie, high-fat diet, diet composed of 35 – 45% of calories from fat, and Pancreatic enzyme replacements for fat digestion, and vitamin supplementation (A, D, E, K)

Croup Definition

• Croup is a viral infection causing inflammation and obstruction of the upper airway, often leading to a characteristic "barking" cough.

Etiology of Croup

• Most commonly caused by parainfluenza virus and affects children under 5 years old.
• Viral croup or laryngotracheitis is most common.
• Recurrent croup (spasmodic or atypical croup) is also common

Acute Laryngotracheitis

• Most commonly occurs in children from 6 months to 5 years of age.
• Peak incidence is at about 2 years of age

Pathophysiology of Croup

• Larynx mucus membranes are tightly adhered to the underlying cartilage
• Edema of the cricoid cartilage area is considered a medical emergency
• Viral croup is primarily caused by subglottic edema from the infection
• Increased resistance to airflow increases the work of breathing and may exacerbate dynamic collapse of the upper airway

Clinical Manifestations of Croup

• Early signs include rhinorrhea, sore throat, and low-grade fever.
• Harsh, (seal like) barking cough.
• Hoarseness and inspiratory stridor.
• Most cases are mild; resolve spontaneously after several more days.
• Upper airway obstruction can occasionally occur → MEDICAL EMERGENCY

Diagnosis of Croup

• The degree of symptoms determines the level of treatment.
• Most children have a barking cough and viral symptoms.
• Prescence of stridor (especially at rest), retractions, or agitation → SICK CHILD
• Estimating Croup Severity Tool → Westley Croup Score; score for the degree of stridor, retractions, air entry, cyanosis, dyspnea, and level of consciousness in the child

Treatment of Croup

• Most children with croup require no treatment.
• Inhalation of humidified air does not improve symptoms in mild to moderate croup.
• Dexamethasone (IM or oral) or Budesonide (nebulized) → improve symptoms within 6 hours
• Racemic epinephrine (nebulized) → improves outcomes with moderate to severe croup

Respiratory Distress Syndrome (RDS) of the Newborn

• RDS is a condition mainly affecting premature infants due to a lack of surfactant, leading to difficulty in breathing and lung collapse.

Additional Epidemiology

• Additional risk factors include Perinatal asphyxia, Meconium aspiration, Second-born twin, Advanced maternal age, Maternal DM
• PROM decreases risks

Etiology of RDS

• Surfactant is not secreted until 20-24 weeks of gestation.
• RDS occurs most often in premature infants or in infants of diabetic mothers or those born via C-sections
• Decreases significantly by 36 weeks.
• Surfactant deficiency can be caused by inadequate hormonal stimulus.
• Significant cause of neonatal morbidity and mortality

Pathophysiology of RDS

• Lack of surfactant causes alveolar collapse at the end of exhalation, leads to increased work of breathing, hypoxia, and possible right-to-left shunting in the heart
• Reduced lung compliance, Reduced FRC, and Poor lung distensibility
• Premature infants are born with surfactant deficiency, underdeveloped lungs and small alveoli, and a weak chest wall

Pathobiochemistry of RDS

• Respiratory acidosis
• Decreased saturated phospholipids
• Low amniotic fluid L/S ratio
• Low surfactant-associated proteins
• Decreased total serum proteins
• Decreased fibrinolysis
• Low thyroxine levels

Pathology of RDS

• Atelectasis
• Injury to epithelial cells, edema
• Membrane contains fibrin and cellular products
• No tubular myelin
• Osmiophilic lamellar bodies (decreased; increased later)

Clinical Manifestations of RDS

• Signs of SDD (RDS) APPEAR WITHIN MINUTES OF BIRTH and include tachypnea.
• Expiratory grunting and Intercostal and subcostal retractions
• Natural course is characterized by progressive hypoxemia and dyspnea that worsens over the first hours of birth

Network Definitions of RDS

• PaO2 < 50 mmHg in room air
• Chest X-Ray is positive

Risk of Preterm Labor and Treatments

• For women at risk of preterm labor, antenatal corticosteroid therapy between 24 and 34 weeks gestation reduces RDS incidence and death of premature infants.
• Maternal steroid therapy significantly reduces incidence of CNS Hemorrhage

For Pre-term Infant

• Prophylactic exogenous surfactant therapy should be give to infants weighing 500 - 2000 grams to treat RDS
• Prevention/treatment of asphyxia
• Supplemental inositol promote maturation of surfactant and prevent adverse neonatal outcomes

Prognosis of RDS

• Most infants recover from RDS within 10-14 days, especially with treatment
• Babies with low birth weight are at higher risk for chronic lung diseases like bronchopulmonary dysplasia.