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Danger of Nasal Congestion in Infants

• Infants and young children have smaller airways compared to adults, making them more susceptible to obstruction from mucosal edema or secretion accumulation.
• Younger children have proportionally larger tonsils, adenoids, and epiglottis, increasing the risk of obstruction when swelling is present.
• Infants, especially up to 2-3 months old, are obligate nose breathers, making nasal congestion a serious threat, particularly during sleep.

Cystic Fibrosis (CF) Overview

• CF is an autosomal recessive inherited disease affecting multiple organs, especially the lungs, pancreas, and digestive system.
• The condition stems from defective chloride ion transport caused by mutations in the CFTR gene.
• The CFTR gene regulates salt and fluid flow in and out of cells.
• The CFTR protein, an activated chloride channel, is found on epithelial cells lining airways, bile ducts, the pancreas, sweat ducts, sinuses, and the vas deferens.
• Mutations in the CFTR gene result in a malfunctioning or absent CFTR protein, leading to a buildup of thick mucus that causes persistent lung infections, pancreatic destruction, and other organ complications.

Etiology of CF

• CF results from mutations in the CFTR gene on chromosome 7.
• Over 2,000 different mutations have been identified, grouped into 6 classes.
• Classes 1-3 mutations are generally more severe, while classes 4-6 are milder, often with pancreatic sufficiency.
• Disease severity correlates with the gene class.
• CF is more common in white individuals; about 28,680 people in the US and 70,000 worldwide have CF.
• Mortality rates are linked to the gene class, with therapy targeting specific classes.
• The median age of diagnosis is 4 months, with over half of the CF population being 18 or older.
• The median predicted age at death is 30.1 years.

Inheritance Pattern of CF

• Both parents must carry a mutated CFTR gene for their child to have CF.
• Carriers have one normal and one mutated gene, but don't show symptoms.
• If both parents are carriers: There is a 25% chance the child will have CF, a 50% chance the child will be a carrier, and a 25% chance the child will neither have CF nor be a carrier.
• If one parent has CF and the other is a carrier: There is a 50% chance the child will have CF and a 50% chance the child will be a carrier.
• CF carriers don't have the disease but can pass the defective gene to their children, with approximately 10 million carriers in the US.

Key Points for Exam

• CF is inherited in an autosomal recessive pattern.
• The most common mutation is F508delCFTR.
• Mortality rates are higher in severe gene classes (1-3) compared to milder classes (4-6).

Teaching

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

Clinical Manifestations of CF

• CF affects the lungs, pancreas, and digestive system, with the most common symptoms involving the respiratory and GI systems.
• The 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 (airways, sinuses, GI tract, pancreas, biliary system, sweat glands, and genitourinary system) thus causing phenotypic variation in clinical manifestations with influences on disease progression and survival
• Respiratory symptoms can include: Persistent cough, excessive sputum production, wheezing, chronic pneumonia, digital clubbing (early sign), barrel chest or persistent crackles (late sign)
• Digital clubbing (bulbous enlargement of the distal segments of the fingers) is also associated with bronchiectasis, pulmonary fibrosis, lung abscess, and congenital heart disease.
• Digestive symptoms include: Poor growth due to nutrient malabsorption and steatorrhea (fatty stools) due to pancreatic insufficiency.

Diagnosis of CF

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

Pathophysiology of CF

• CF is a multi-organ disease affecting the airways, digestive tract, and reproductive organs.
• Lungs: Defective chloride transport leads to thick, sticky mucus, blocking airways, leading to infection and inflammation. Common infections are caused by Pseudomonas aeruginosa and Staphylococcus aureus. That mucus is difficult to clear, leading to chronic inflammation and structural damage like bronchiectasis (airway dilation).
• Pancreas: 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; the most common mutation is F508delCFTR.

Complications of CF

• Chronic respiratory infections and bronchiectasis.
• Diabetes from pancreatic damage.
• Pulmonary hypertension and cor pulmonale due to pulmonary vascular remodeling (localized hypoxia and arteriolar vasoconstriction).
• The most important effects are on the lungs (respiratory failure is almost always the cause of death).
• Hemoptysis (life-threatening) due to inflammation associated with bronchiectasis, leading to erosion of enlarged bronchial arteries.
• Peripheral bullae development (due to airway obstruction and weakening of airway wall) leading to pneumothorax.
• Microabscess formation, patchy consolidation leading to pneumonia, peribronchial fibrosis, and cyst formation.
• Typical features of CF lung disease include: Mucus plugging due to increased numbers and size of goblet cells, altered physiochemical properties of mucus, and impaired mucociliary clearance, leading to increased mucus production. Consequently, Mucus is dehydrated and viscous (defective chloride secretion and excess sodium absorption).
• The periciliary fluid layer is depleted in volume, impairing cilia mobility, allowing mucus to adhere to airway epithelium along with bacteria and injurious byproducts from neutrophils.
• Chronic inflammation: Neutrophils are present in great excess in airways, releasing damaging oxidants and proteases (e.g., elastase), directly damaging lung structural proteins, and remodeling the airway leading to bronchiectasis development.
• Neutrophils promote inflammation and induce airway cells to produce interleukin-8. This attracts more neutrophils, stimulates mucus secretion, and destroys immunoglobulin G and complement components, impairing opsonization and phagocytosis of pathogens.
• Chronic infection of small airways: Bacteria then form biofilms, promoting chronic endobronchial infection (the large majority of children have this). Staphylococcus aureus, Burkholderia cepacian, and Pseudomonas aeruginosa colonize 75% of airways with CF.
• Colonies of pseudomonas adopt a mucoid phenotype, organize themselves into adherent biofilms, making it difficult for antibiotics and local defenses to reach them. The biofilm resists β-lactam antibiotics, and rapid mutation makes them antibiotic-resistant.

Treatment of CF

• The primary focus of treatment is on pulmonary health and nutrition.
• Pulmonary care includes: Chest physiotherapy (CPT), high-frequency chest wall oscillation, and PEP devices to help clear mucus.
• Medications include: Aerosol therapy with bronchodilators, dornase alfa (to break down mucus), and hypertonic saline (liquifies mucus) and antibiotics (oral, inhaled, intravenous) to treat different pathogens.
• Other medications: 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
• Nutritional care involves: A high-calorie, high-fat diet (35 – 45% of calories from fat).
• Pancreatic enzyme replacements for fat digestion and Vitamin supplementation (A, D, E, K) to maintain vitamin D serum concentrations at 30ng/ml.
• Controlling fat malabsorption where Weight-For-Length value is > 50th percentile (children younger than 2 years of age) and BMI > 50th percentile (children older than 2 years of age).
• Approximately 90% of children have pancreatic insufficiency due to abnormal ion transport (decreased fluid and bicarbonate secretion from pancreatic acinar cells), thickened secretions plugging smaller pancreatic ducts, and eventual autodigestion or atrophy of acinar cells. They MUST take exogenous pancreatic enzymes with meals and snacks to absorb nutrients and control malabsorptive symptoms (particularly fat absorption).
• A fecal pancreatic elastase-1 is a common diagnostic test for evaluation pancreatic insufficiency.

Croup Definition

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

Etiology of Croup

• Most commonly caused by the parainfluenza virus.
• Affects children under 5 years old.
• Viral croup (laryngotracheitis) is the most common type
• Another type of croup is called Recurrent croup (spasmodic croup or atypical croup)

Recurrent Croup

• Defined as two or more episodes of croup with similar symptoms, except it recurs without symptoms of a respiratory tract infection.
• Resolves as quickly as it develops.
• Usually occurs in older children.
• Etiology: Unknown; some cases present with an underlying congenital obstruction or airway narrowing (e.g., laryngomalacia or tracheomalacia); also associated with GERD or asthma.

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

• The larynx mucus membranes are tightly adherent to the underlying cartilage, and the subglottic space is looser, allowing accumulation of mucosal and submucosal edema.
• The cricoid cartilage is structurally the narrowest point of the airway; edema of this area is a critical emergency. Viral Croup is primarily caused by subglottic edema from the infection.
• Increased resistance to airflow leads to an increased work of breathing, generating more negative intrathoracic pressure, which 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 and resolve spontaneously after several days.
• Upper airway obstruction can occasionally occur and this is a medical emergency

Diagnosis of Croup

• The degree of symptoms determines the level of treatment
• Most children have a barking cough and viral symptoms and may need no specific treatment.
• The presence of stridor (especially at rest), retractions, or agitation indicates a sick child.
• There is an Estimating Croup Severity Tool called the Westley Croup Score. This provides a cumulative score for the degree of stridor, retractions, air entry, cyanosis, dyspnea, and level of consciousness in the child. The degree of seriousness of croup is also classified as mild, moderate, and severe.

Treatment of Croup

• Most children with croup require no treatment.
• The 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; it stimulates α- and β-adrenergic receptors, decreasing airway secretions and mucosal edema.
• The use of Epinephrine is a temporary treatment until concomitantly given corticosteroids begin to work. Children given nebulized epinephrine should be closely observed for 2 to 3 hours to ensure they remain stable.
• Oxygen should be administered. Heliox (helium/oxygen mixture 80:20 or 70:30) for severe cases of croup
• In rare cases, placement of an ET Tube is required for a patient with severe croup or recurrent croup
• Recurrent croup requires evaluation for anatomic abnormalities and the presence of associated diseases

Respiratory Distress Syndrome (RDS) of Newborn

• Respiratory Distress Syndrome (RDS), previously called hyaline membrane disease, is a condition that mainly affects premature infants due to a lack of surfactant, leading to difficulty in breathing and lung collapse.
• Additional epidemiology includes: Worldwide, perinatal asphyxia, meconium aspiration, advanced maternal age, maternal DM if less than 37 weeks.

Etiology of RDS

• Surfactant is NOT secreted until approximately 20-24 weeks gestation.
• Most often occurs in premature infants, especially those born before 36 weeks gestation; it is common in infants of diabetic mothers or those born via C-sections, occurring in 50-60% of infants born at 29 weeks' gestation and decreases significantly by 36 weeks.
• RDS is a significant cause of neonatal morbidity and mortality.
• The incidence increased in U.S. in past 2 decades and is more common in boys and African Americans
• Death rates have declined due to antenatal steroid therapy and postnatal surfactant therapy.

Pathophysiology of RDS

• The lack of surfactant causes the alveoli to collapse at the end of exhalation, reducing lung compliance. This leads to increased work of breathing, hypoxia, and possible right-to-left shunting in the heart.
• Reduced lung compliance with poor lung distensibility and poor alveolar stability.
• Right-to-left shunts with ineffective pulmonary blood flow.
• Patent ductus arteriosus contributes to the above.
• If hypotensive and hypoxic, poor peripheral perfusion, poor renal perfusion, and myocardial malfunction.

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 early; increased later).

Premature infants are born with

• Surfactant deficiency (main cause): Surfactant lipoproteins have detergent-like effects, separating liquid molecules inside the alveoli, decreasing alveolar surface tension; without it, alveoli collapse at the end of exhalation, resulting in low alveolar surface area available for gas exchange.
• Underdeveloped lungs and small alveoli are difficult to inflate with thick walls of alveoli with inadequate capillary blood supply, leading to significantly impaired gas exchange.
• A weak chest wall (highly compliant) means the rib cage tends to collapse inward with respiratory effort, leading to atelectasis, and requires a significant negative inspiratory pressure to open alveoli with each breath (difficult for neonate to overcome), leading to significant hypoxemia.
• Increased work of breathing and low tidal volume lead to alveolar hypoventilation and hypercapnia, causing pulmonary vasoconstriction and increased intrapulmonary resistance and shunting and hypoperfusion of the lung and ineffective pulmonary blood flow
• Increased pulmonary vascular resistance can cause partial return to fetal circulation with right-to-left shunting of blood through the ductus arteriosus and foramen ovale. Hypoperfusion of tissues and hypoxemia can lead to metabolic acidosis.
• The condition is further complicated by an increase pulmonary capillary permeability
• Premature infant with SDD require positive pressure mechanical ventilation with high oxygen content damages the alveolar epithelium (e.g. barotrauma and oxygen toxicity) This leads to leakage of plasma protein into alveoli and pulmonary edema and Fibrin deposits in air spaces, creating the appearance of hyaline membranes, plasma proteins leaked into the air space inactivate any surfactant that is present.

Clinical Manifestations of RDS

• Signs of SDD (RDS) appear within minutes of birth and include: Tachypnea (RR > 60 breaths per minute), Expiratory grunting, Intercostal and subcostal retractions, Nasal flaring, and Cyanosis.
• The natural course is characterized by progressive hypoxemia and dyspnea that becomes more severe over the first hours of birth.
• Apnea and irregular respirations indicate the infant is becoming tired.
• The severity of hypoxemia and difficulty in providing adequate supplemental oxygenation is determined by the Vermont Oxford Network definitions of RDS.
• Clinical manifestations peak within 3 days, after which there is gradual improvement with appropriate treatment.

Additional Clinical Manifestations

• Onset near the time of birth with a course to death or improvement by 3 to 5 days.
• Systemic hypotension.
• Fine inspiratory rales.
• Hypothermia.
• Peripheral edema and pulmonary edema.

Diagnosis of RDS

• Clinical signs like fast breathing, grunting, and cyanosis.
• Chest X-ray: Shows a "ground glass" appearance (patchy areas in the lungs)
• Amniotic fluid tests: Can estimate lung maturity (L/S ratio).

Risk of Preterm Labor & Treatments

• For women at risk of preterm labor: Antenatal corticosteroid therapy is given (for more than 24 hours) between 24 and 34 weeks gestation to greatly reduce the incidence of RDS and death of premature infants.
• Glucocorticoids stimulate lung maturation, particularly type 1 and type 2 pneumocytes, speeding up the production of surfactant.
• Betamethasone is often given to women with a singleton pregnancy between 34 0.7 and 35 6/7 weeks gestation at imminent risk of preterm birth within 7 days to improve outcomes.
• Maternal steroid therapy significantly reduces the incidence of SDD, bronchopulmonary dysplasia, CNS hemorrhage, and neonatal mortality.

For Pre-Term Infant

• Prophylactic exogenous surfactant therapy: Infants weighing between 500-2000 grams should receive surfactant treatment within 15-30 minutes of birth to prevent or treat RDS; this can be administered through a catheter, nebulizer, or nasal CPAP.

Delivery of Pre-Term Infant

• Prevention of premature birth is the ultimate treatment for surfactant deficiency disorder (SDD)
• Other preventative measures include prevention of asphyxia and surfactant replacement (prophylactically within 15 min after birth, or early rescue within 60 min after birth)

Supportive Care for Infant

• Oxygen administration.
• Mechanical ventilation can trigger a proinflammatory state, contributing to the development of chronic lung disease (e.g., bronchopulmonary dysplasia [BPD]).
• Strategies evaluated for lung protective mechanisms include: Greater reliance on nasal continuous positive airway pressure [NCPAP] to prevent lung injury, permissive hypercapnia, lower oxygen saturation targets, modulation [LOWER] of tidal volume settings, and the use of high-frequency oscillation or jet ventilation.
• Improved outcomes are seen with ventilation using mixtures of oxygen and nitric oxide / helium, which improve gas exchange and reduce airflow resistance.
• Rescue surfactant therapy is only given to preterm infants with established RDS, most often administered within the first 12 hours after birth (when specified criteria for severity is met). It produces a dramatic improvement in oxygenation, decreased incidence of SDD death, pneumothorax, and pulmonary interstitial emphysema.
• It can be considered a complimentary treatment with antenatal glucocorticoids for an additive effect on improving lung function.
• Supplemental inositol can promote the maturation of surfactant and prevent adverse neonatal outcomes.

Prognosis of RDS

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