Congenital Developmental Respiratory Disorders.pdf

Congenital Developmental Respiratory Diseases The most commonly encountered congenital lung anomalies include: 1. Lung agenesis-hypoplasia complex (pulmonary underdevelopment) 2. Congenital pulmonary airway malformations (CPAM) 3. Bronchogenic cysts 4. Scimitar syndrome 5. Bronchopulmonary sequestra...

Congenital Developmental Respiratory Diseases The most commonly encountered congenital lung anomalies include: 1. Lung agenesis-hypoplasia complex (pulmonary underdevelopment) 2. Congenital pulmonary airway malformations (CPAM) 3. Bronchogenic cysts 4. Scimitar syndrome 5. Bronchopulmonary sequestration. The most common upper airway congenital anomalies are laryngo-tracheomalacia and trachea-esophageal fistula. Recognizing the antenatal and postnatal features of these abnormalities, based on clinical presentation and imaging, is necessary for optimal prenatal counseling and appropriate periand postnatal management. Pathogenesis Due to defective foregut budding and differentiation and / or fetal airway obstruction with secondary pulmonary dysplastic changes. Embryology of the respiratory system development • • • Five phases: embryonic, pseudo-glandular, canalicular, saccular, and alveolar. The embryonic phase: begins in 4th week of gestation with the formation of the respiratory diverticulum (laryngotracheal bud) from the ventral wall of the primitive foregut. o As the lung bud elongates, lateral invagination of the mesoderm gives rise to the tracheoesophageal septum, which separates the esophagus and trachea. o Between 5 - 7 weeks gestation, the distal end of the laryngotracheal bud bifurcates into two lung buds that grow to form the right and left mainstem bronchi, which in turn branch into lobar bronchi. The pseudo-glandular phase (7 - 16 weeks gestation): formation of segmental and subsegmental bronchi. 1 o Through a series of divisions, the bronchi give rise to bronchioles, and each terminal bronchiole gives rise to a number of alveolar ducts and alveoli. o By the end of the pseudo-glandular phase, all the bronchi are formed. • • • Canalicular phase (16 to 24 weeks gestation): distal acinar unit develops and further airspaces are being “canalized” and approximated by a network of capillaries. Saccular phase (∼24 to 36 weeks gestation): the alveoli and terminal sacs continue to develop, with compression of intervening interstitium and the beginning of alveolar septation. US image shows a normal fetal diaphragm (arrows), which is seen as a smooth, hypoechoic band of tissue separating the thorax and the abdomen. Note that the fetal lung (L) appears slightly more echogenic than the liver (Li). Alveolar phase (after 36 weeks gestation): appearance of fully mature alveoli commences, with the majority of alveoli being formed during the first 2 years of life. 2 A. Pathologies associated with congenital developmental lung disease 1. Oligohydramnios 2. Polyhydramnios 3. Micrognathia 1. Oligohydramnios • • • Definition: amount of amniotic fluid is less than expected for gestational age Etiology o Fetal anomalies ▪ Urethral obstruction (e.g., posterior urethral valves) ▪ Bilateral renal agenesis ▪ Autosomal recessive polycystic kidney disease (ARPKD) o Maternal conditions ▪ Placental insufficiency ▪ Late or postterm pregnancies (> 42 weeks of gestation) ▪ Premature rupture of membranes Diagnosis o Ultrasound: determine amniotic fluid and assess for fetal anomalies o Amniotic fluid index (AFI): a semiquantitative tool used to assess amniotic fluid volume (normal range: 8–18 cm) ▪ Oligohydramnios: ≤ 5 3 Ultrasound fetal (amniotic fluid index) Amniotic fluid index (AFI) is part of the fetal biophysical profile. The deepest pocket of amniotic fluid without fetal parts or umbilical cord is measured in centimeters in each quadrant. The AFI is the sum of the four measurements. P: placenta • Complications o Intrauterine growth restriction o Birth complications (e.g., umbilical cord compression) o Potter sequence 2. Polyhydramnios Polyhydramnios • Definition: excessive amniotic fluid volume expected for gestational age • Etiology o Typically idiopathic o Fetal anomalies o Gastrointestinal (e.g., esophageal atresia, duodenal atresia and stenosis): reduced swallowing and absorption of amniotic fluid o CNS: anencephaly; leads to impaired swallowing of amniotic fluid o Pulmonary: cystic lung malformations o Multiple pregnancy: twin-to-twin transfusion syndrome 4 • • o Fetal anemia o Maternal conditions o Diabetes mellitus o Rh incompatibility Diagnostics o Physical examination: abdominal girth and uterine size large for gestational age o Ultrasound ▪ AFI ≥ 25 ▪ Assess for fetal anomalies o Others: Rh screen Complications o Fetal malposition o Umbilical cord prolapse o Premature birth 3. Micrognathia Embryological development of facial structures • Pharyngeal groove: ectodermal origin • Pharyngeal arch o Central mesenchymal core, which contains a nerve, an artery, and cartilage o Derived from the neural crest and mesoderm • Pharyngeal pouch: endodermal origin Derivatives from the outer to the inner layer (Groove: ectoderm; Arch: mesoderm and neural crest; Pouch: endoderm): GAP 5 B. Congenital developmental lung disorders 1. Lung aplasia 2. Pulmonary hypoplasia 3. Bronchogenic cysts 4. Pulmonary sequestration/accessory lung 5. Congenital pulmonary airway malformations (CPAM) 1. Lung aplasia 6 Pulmonary aplasia. (a) Frontal chest radiograph depicts the trachea (white arrow) and the right main bronchus (arrowhead); however, the left main bronchus is not seen. There is leftward mediastinal shift. Compensatory hyperinflation of the right middle lobe extending into the left hemithorax is also noted (black arrow). (b) Coronal CT scan shows a blind-ending left main bronchus (arrowhead) with absence of the left lung parenchyma. Pulmonary aplasia. Unenhanced CT scan shows the main pulmonary artery (MPA) and right pulmonary artery (RPA), but the left pulmonary artery is not seen. 2. Pulmonary hypoplasia a. Bilateral renal agenesis causing oligohydramnios b. Potter sequence c. Prune-belly syndrome d. VACTERL e. Williams syndrome • • Underdevelopment of the lungs characterized by a decreased number of alveoli and small airways. Primary or secondary. o Primary (no apparent cause) = much less common than secondary hypoplasia. o Secondary = result of an intrathoracic or extrathoracic process limiting the lung development: ▪ Intrathoracic causes: • Most common = congenital diaphragmatic hernia (left sided in 75%–90% of cases, right sided in 10%, and bilateral in 5%). Left-sided congenital diaphragmatic hernia is relatively easier to detect due to the presence of an identifiable fluid-filled stomach in the thorax. In right-sided congenital 7 ▪ diaphragmatic hernia, the liver herniates into the chest, which may be difficult to detect due to the solid echotexture of the liver. Extrathoracic: • Bilateral renal agenesis causing oligohydramnios • Potter sequence • Prune-belly syndrome • VACTERL a. Congenital diaphragmatic hernia = impaired development and/or fusion of embryonic structures (pleuroperitoneal membrane) → defect in the diaphragm persists during fetal development → displacement of abdominal contents into the pleural cavity ; → compression of lung tissue; → pulmonary hypoplasia • Because the liver protects the right hemidiaphragm, diaphragmatic hernias most commonly occur on the left side! 8 Clinical presentation: Respiratory distress (e.g., nasal flaring, tachypnea, cyanosis, intercostal retractions, grunting) Barrel-shaped chest, scaphoid abdomen (concave anterior abdominal wall), and auscultation of bowel sounds in the chest Absent breath sounds on the ipsilateral side Possible syndromic dysmorphism Diagnosis: • Antenatal ultrasound: most cases are diagnosed on routine antenatal ultrasound o Fluid-filled stomach/bowel seen in the thorax o Esophageal compression can cause polyhydramnios o Hydrops fetalis may also be seen in severe cases • Chest x-ray o Abdominal contents, air/fluid-filled bowel, and poorly aerated lung in the ipsilateral hemithorax 9 10 DDx: • Prenatal CDH o Bronchogenic cysts ▪ Clinical features ▪ Usually asymptomatic ▪ In some cases, failure to drain can cause airway compression with significant respiratory distress or recurrent respiratory tract infections. ▪ Diagnostics ▪ Chest x-ray: discrete, round, and sharply defined fluid-filled densities; infection indicated by air inclusions ▪ Pathogenesis: abnormal budding of the ventral foregut → dilation of the terminal or large bronchi → unilateral or bilateral unilocular cysts • Postnatal CDH o Other causes of pulmonary hypoplasia (e.g., oligohydramnios, renal hypoplasia) b. Bilateral renal agenesis with oligohydramnios Pulmonary hypoplasia due to bilateral renal agenesis. (a) Transverse fetal US image shows a small chest with severe oligohydramnios. A small pericardial effusion (calipers) is also seen. (b) AP chest x-ray demonstrates bilateral pulmonary hypoplasia due to severe oligohydramnios secondary to bilateral renal agenesis. Note the low lung volumes and the bell-shaped configuration of the thorax. 11 c. Potter sequence Etiology • Chronic placental insufficiency • ↓ Renal output (e.g., due to bilateral renal agenesis, ARPKD, obstruction of posterior urethral valves) Pathophysiology: oligohydramnios → intrauterine compression and decreased amniotic fluid ingestions → ↓ space for fetal development → internal and external deformations Clinical features • Pulmonary hypoplasia (cause of death due to severe neonatal respiratory insufficiency) • Craniofacial abnormalities (e.g., prominent epicanthal and infraorbital folds, flattened nose, receding chin, low set ears) • • • • • Wrinkling of the skin Limb anomalies (e.g., bowed legs, clubbed feet) Potter babies cannot Pee. POTTER sequence: Pulmonary hypoplasia (lethal), Oligohydramnios (origin), Twisted facies, Twisted skin Classic form: extremity deformities + renal agenesis. 12 d. Prune belly syndrome (PBS) • = Triad syndrome of deficient abdominal musculature, cryptorchidism, and genito-urinary tract abnormalities. • Range of severity: death in the perinatal period to an almost normal life. 1. Abdominal wall musculature: • In rare cases, completely absent (skin, subcutaneous fat and a single fibrous layer may be all that is overlying the peritoneum) • In the lower part of the abdominal wall. • Mainly affected rectus muscles and internal and external obliques => severe constipation. due to ineffective Valsalva maneuver. 2. Urinary tract abnormalities: • Hydroureteronephrosis: o Almost always present o Mostly bilateral. o Due to: ▪ Posterior urethral valves ▪ Vesicoureteral reflux (VUR) ▪ Histologic deficiency of smooth muscle and preponderance of fibrous tissue in ureters leading to ineffective peristalsis => ureteral urinary stasis and poor bladder emptying. • Severe hydronephrosis => renal insufficiency in utero => oligohydramnios, pulmonary hypoplasia, micrognathia, facial wrinkling (Potter sequence) in >58% of the patients • Pulmonary hypoplasia is the most significant complication in newborns with PBS. • 75% patients will have at least one documented urinary tract infection (UTI), and one-third will develop pyelonephritis. 3. Cryptorhisdism in male infants: • Testes lie intra-abdominally, adjacent to the dilated ureters at the level of iliac arteries. • Patients with PBS require interprofessional management, an aggressive bowel regimen and prevention of UTI’s. 13 e. VACTERL association • • • defect during the first semester development of embryonic mesoderm Vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb abnormalities poor prognosis. Its early detection allows discussion of management options, including medical termination of pregnancy. f. Williams syndrome (WS) • • • • • • • • • Multisystem, contiguous gene deletion syndrome caused by a recurrent microdeletion of 7q11.23. Autosomal dominant but most cases = de novo mutations "Elfin" facies: remarkably uniform, with eyebrows that flare medially, depressed nasal bridge, prominent epicanthal folds, anteverted nares are anteverted, prominent lips and full cheeks. Cardiovascular anomalies (rare, but associated with sudden death): supravalvar aortic stenosis and peripheral pulmonary artery stenosis. Hypertension: 50% of patients with WS Metabolic and endocrine abnormalities: o Hypercalcemia o Hypothyroidism o Adult patients: type 2 diabetes mellitus. Cognitive: intellectual disability accompanied by a friendly, social personality. Short stature. Genitourinary abnormalities include congenital anomalies of the kidney and urinary tract (CAKUT): o Dysfunctional voiding o Nephrocalcinosis due to hypercalciuria, and recurrent urinary tract infections o Renal aplasia or hypoplasia => oligohydramnios => pulmonary hypoplasia 14 Chromosome 7 (Williams) 3. Bronchogenic cysts Epidemiology • rare (5-10% of pediatric mediastinal masses). • Incidence of mediastinal cysts is equal between the sexes; • Intrapulmonary cysts have a male predilection. Clinical presentation • Asymptomatic -> found incidentally when the chest is imaged. • When large, mass effect may result in bronchial obstruction leading to air trapping and respiratory distress. • Also symptomatic when it becomes infected. Pathology • Form as a result of abnormal budding of the bronchial tree during embryogenesis (between 4th-6th weeks) => are lined by secretory respiratory epithelium = cuboid or columnar ciliated epithelium. • The wall = tissues similar to that of the normal bronchial tree, including cartilage, elastic tissues, mucous glands, and smooth muscle. • Do not usually communicate with the bronchial tree and are therefore typically not airfilled. • Contain fluid (water) with variable amounts of proteinaceous material, blood products, and calcium oxalate => increased attenuation mimicking solid lesions. 15 • • Occasionally a communication may develop following infection or intervention=> air-filled cystic structure +/- an air-fluid level They are rarely multiple. Imaging • Plain radiograph o soft-tissue density rounded structures, sometimes with compression of surrounding structures. Occasionally such compression can lead to air-trapping and a hyperlucent hemithorax. o As the cysts may contain Ca oxalate, dependent layering of calcific density material may on occasion be seen. • CT scan o Typically appear as well-circumscribed spherical or ovoid masses of variable attenuation due to variable fluid composition. • MRI o Sometimes performed for confirmation, especially with atypical cases. o Mostly homogeneous. Treatment and prognosis • Conservative with follow up for small lesions (because they tend to grow) • Surgical excision due to tendency to become infected or undergo malignant transformation. • Alternatively, use transbronchial or percutaneous aspiration under CT guidance (diagnostic and treatment). Complications • fistula formation with the bronchial tree • ulceration of the cyst wall • secondary bronchial atresia • superimposed infection • hemorrhage • malignant transformation - very rare Differential diagnosis • other congenital cysts and malformations • pericardial cyst • cystic hygroma and lymphangioma • neurenteric cyst • anterior or lateral meningocoele • oesophageal duplication cyst • thyroid colloid cyst • thymic cyst • intrathoracic pancreatic pseudocyst • abscess 16 • • enlarged lymph nodes, especially if centrally necrotic pulmonary masses • congenital pulmonary airway malformation (CPAM) • pulmonary sequestration Distribution The most common location is the middle mediastinum (65-90%). • mediastinal (~70%) o usually does not communicate with the tracheobronchial tree o subcarinal, right paratracheal and hilar locations most common o approximate incidence includes ▪ carinal: ~50% ▪ paratracheal: ~20% ▪ oropharyngeal wall: ~15% ▪ retrocardiac: ~10% • parenchymal (intrapulmonary) o typically, perihilar o predilection for lower lobes • other uncommon locations o neck o cutaneous o pericardium o extending across the diaphragm and appearing dum-bell shaped o retroperitoneal: tend to be in a subdiaphragmatic or peripancreatic distribution, usually to the left of the midline Ultrasound with Doppler in transverse B-mode: avascular cystic lesion (arrow) in the left lung adjacent to the ductus arteriosus 17 Contrast material–enhanced postnatal CT scan shows a well-circumscribed unilocular waterattenuation cyst in the middle mediastinum. The cyst has smooth, imperceptible walls with no enhancement and was pathologically confirmed to be a bronchogenic cyst. Resected translucent bronchogenic cyst specimen (Ellen M. Chung, LTC, MC, USA, Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC.) 18 H-E stain of a bronchogenic cyst lined by respiratory epithelium and containing cartilage plates, bronchial glands, and smooth muscle within its wall. 4. Pulmonary sequestration/accessory lung = refers to the aberrant formation of segmental lung tissue with no connection with the bronchial tree or pulmonary arteries = bronchopulmonary foregut malformation (BPFM). Types: • intralobar sequestration (ILS) • extralobar sequestration (ELS) o extralobar intrathoracic o extralobar subdiaphragmatic Clinical presentation o ELS: presents in newborns as respiratory distress, cyanosis, infection o ILS: presents in late childhood or adolescence with recurrent pulmonary infections. Pathology Pulmonary sequestrations have no communication with the tracheobronchial tree can be divided based on the relationship of the aberrant segmental lung tissue to the pleura: • ILS: o majority (75-85%) of all sequestrations o present later in childhood with recurrent infections o closely connected to the adjacent normal lung and do not have a separate pleura • ELS o less common (15-25% of all sequestrations 4,5,7) o usually present in the neonatal period with respiratory distress, cyanosis, or infection o recognised male predilection M: F ratio ~4:1 19 o can be infradiaphragmatic in ~10% of cases o separated from any surrounding lung by its own pleura Bronchioles (1) lined by ciliated columnar epithelium and alveoli (2) Bronchiole (1) lined by ciliated columnar epithelium 20 Pulmonary sequestration: immature lung tissue with non-cartilaginous airways and dilated simplified The abnormal lung tissue has a systemic arterial supply from a branch of the aorta. For the venous supply: • ILS: mostly via the pulmonary veins into left atrium • ELS: mostly via systemic veins into the right atrium Genetics • Almost all cases occur sporadically. Location • Preferentially affects the lower lobes. • 60% of intralobar sequestrations affect the left lower lobe, and 40% the right lower lobe. • Extralobar sequestrations almost always affect the left lower lobe, however, ~10% of extralobar sequestrations can be subdiaphragmatic 8. Associations • Associated disease is common with the extralobar type (50-60%): • congenital pulmonary airway malformation (CPAM) => hybrid lesion • congenital heart disease • congenital diaphragmatic hernia • Scimitar syndrome 21 Imaging Plain radiograph • triangular opacity in the affected segment • cystic spaces if infected Ultrasound • The sequestrated portion of the lung is usually more echogenic than the rest of the lung. On antenatal ultrasound, an extralobar sequestration may be seen as early as 16 weeks gestation and typically appears as a solid well-defined triangular echogenic mass 8. Colour Doppler may identify a feeding vessel (in-utero cases) from the aorta. If the sequestration is subdiaphragmatic, it may appear as an echogenic intra-abdominal mass. CT • cross-sectional imaging frequently demonstrates the arterial supply by the descending aorta • Angiography (DSA) not part of the routine investigation but is the gold standard in determining arterial supply. 22 MRI Treatment and prognosis • Surgical resection: 1. ELS: remove sequestration with the separate pleural investments, sparing normal lung tissue 2. ILS: segmental resection or even lobectomy will be necessary. • Coil embolization of arterial supply • Spontaneous involution. Complications • frequent respiratory tract infection • in neonates can be complicated by high output cardiac failure Differential diagnosis General imaging differential considerations include: • persistent pneumonia • pulmonary abscess • congenital pulmonary airway malformation (CPAM) • bronchogenic cyst • pulmonary arteriovenous malformation • scimitar syndrome o small lung with ipsilateral mediastinal shift o tubular structure parallelling the right heart border in the shape of a Turkish sword (“scimitar”) o right heart border may be blurred and may be mistaken by a triangular-shaped sequestration 23 Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID: 10689 24 5. Congenital pulmonary airway malformations (CPAM) = CPAMs are a heterogeneous group of cystic and non-cystic lung masses of segmental lung tissue with abnormal bronchial proliferation, which largely result from early airway maldevelopment. = part of the spectrum of bronchopulmonary foregut malformations. = Previously known as congenital cystic adenomatoid malformations (CCAM). ~25% of congenital lung lesions (incidence is ~ 1:1500-4000 live births) • male predominance. Clinical presentation • The diagnosis is usually either made on antenatal ultrasound, or in the neonatal period on the investigation of progressive respiratory distress. • If large, they may cause pulmonary hypoplasia. • If small, diagnosed late, even adulthood, due to recurrent chest infection. Pathology • The condition results from failure of normal bronchoalveolar development with a hamartomatous proliferation of terminal respiratory units in a gland-like pattern (adenomatoid) without proper alveolar formation. • Histology: adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands. • Have intracystic communications • Unlike bronchogenic cysts, have a connection to the tracheobronchial tree. Subtypes Five subtypes are currently classified, mainly according to cyst size: • type 0 = very rare, lethal postnatally • type I = most common (70% of cases), with one or more dominant large cysts that may be surrounded by smaller cysts 25 • type II = 15-20% of cases, with cysts <2 cm in diameter, associated with other abnormalities o renal agenesis or dysgenesis o pulmonary sequestration o congenital cardiac anomalies o congenital cardiac anomalies • type III o ~10% of cases o microcysts: <5 mm in diameter o typically involves an entire lobe o has a poorer prognosis • type IV = global arrest of lung development => unlined cyst Location Usually unilateral and involve a single lobe. Associations • hybrid lesion: i.e. CPAM and pulmonary sequestration • renal agenesis • polyhydramnios • hydrops fetalis • lung malignancy Imaging The appearance of CPAMs will vary depending on the type. 1. Antenatal ultrasound = isolated cystic or solid intrathoracic mass (hyperechoic, in type III CPAM). • There can be a mass effect where the heart may appear displaced to the opposite side. • Detects hydrops fetalis and polyhydramnios. 2. Plain radiograph • Type I and II CPAMs: multicystic (air-filled) lesion. o Large lesions => mass effect => mediastinal shift, depression, inversion of the diaphragm. o In the early neonatal period, the cysts may be completely or partially fluid-filled => appear solid or with air-fluid levels. o May change in size in time -> expand from collateral ventilation via pores of Kohn. • Type III lesions = solid. CT scan: • Accurately delineates the location and extent of the lesion. • CT angiography = to identify systemic arterial supply in surgical candidates. Treatment and prognosis 26 • Surgery o Elective lobectomy = treatment of choice in symptomatic patients with early respiratory compromise and recurrent infection. o Type I lesions have the best prognosis. • In small stable asymptomatic lesion watch and wait. There are reports of spontaneous regression, particularly in those serially followed up on antenatal ultrasound. Complications Potential postnatal complications include: • recurrent pneumothorax • hemopneumothorax • pyo-pneumothorax • malignancies Potential in utero complications include: • hydrops fetalis if severe compression of the fetal heart or great vessels • compression of the normal fetal lung => pulmonary hypoplasia Differential diagnosis General imaging differential considerations include: • bronchogenic cyst: Unilocular, does not usually communicate with the bronchial tree, and are therefore typically not air-filled • pulmonary sequestration: has systemic arterial supply • congenital diaphragmatic herniation: bowel loops within a hemithorax • congenital lobar emphysema (congenital lobar overinflation): hyperlucent and hyperinflated lung segment, with no cystic or solid components • localized congenital cystic bronchiectasis For type I lesions on CT also consider: cicatrization collapse with scarring and traction bronchiectasis. 27 28 Primary ciliary dyskinesia • • Definition: rare autosomal recessive disorder characterized by absent or dysmotile cilia caused by a defect in the dynein arm of microtubules Clinical features 29 o o o o o o o • • • Chronic productive cough Recurrent otitis, sinusitis, and nasal polyps Bronchiectasis Conductive hearing loss Displaced heart sounds Infertility in men due to decreased sperm motility as a result of defective flagella Reduced fertility in women (and rarely ectopic pregnancy) due to defective cilia in fallopian tubes o Kartagener syndrome: classic triad of situs inversus, recurrent sinusitis, and bronchiectasis Diagnostics o Nasal nitric oxide test: reduced nasal nitric oxide (screening test) o Genetic tests for dynein arm mutations o Chest x-ray: bronchiectasis, dextrocardia, and situs inversus You can memorize the cause of Kartagener syndrome by thinking of Kartagener's restaurant that only has 'take-out' service because there is no dine-in (dynein). Kartagener syndrome is a subtype of primary ciliary dyskinesia characterized by the triad of situs inversus, chronic sinusitis, and bronchiectasis. B. Developmental abnormalities of the upper airways 1. Tracheoesophageal fistula and esophageal atresia 30 2. Laryngomalacia and tracheomalacia a. Laryngomalacia (LM) = most common laryngeal anomaly in infants (incidence 1:2100–2600 children). = collapse of the supraglottic structures during inspiration. It is distinct from tracheomalacia (an abnormally compliant trachea), which is far less common. Laryngomalacia causes inspiratory stridor, whereas tracheomalacia causes expiratory or biphasic stridor. In addition, tracheomalacia is often associated with other congenital malformations such as tracheoesophageal fistula or vascular rings. Etiology — Proposed mechanisms include: Delayed maturation or "hypotonia" of the supporting cartilaginous structures of the larynx • Redundant soft tissue in the supraglottis • A foreshortened or tight aryepiglottic fold • Underlying neuromuscular disorders • Supraglottic inflammation or edema (A) Flexible laryngoscopy during inspiration. Note collapse of the epiglottis. (B) Flexible laryngoscopy during expiration. Note the omega-shaped epiglottis. Main symptom is stridor: • In neonates: intermittent low-pitched, "wet" inspiratory stridor that worsens in supine position and during sleeping or feeding. 31 • Loudest at 4-8 months of age and resolves by 12 to 18 months Hoarseness is not associated with stridor! Associated with: • Snoring and/or sleep-disordered breathing • severe respiratory distress: respiratory failure, apnea, cyanosis, and feeding disorders: swallowing • feeding difficulties with choking, regurgitation, and microaspiration events • gastro-esophageal reflux disease (GERD) • failure to thrive due to increase work load while breathing and at the same time greater energy expenditure (89%) Diagnosed and classified by its laryngoscopic appearance: type 1—prolapse of the mucosa overlying the arytenoid cartilages, type 2—foreshortened aryepiglottic folds, and type 3— posterior displacement of the epiglottis. Increased severity if associated with comorbidities: general hypotonia in neurological diseases, increased work of breathing in cardiac diseases, and anatomic airway obstruction in micrognathia. If severe, may be accompanied by synchronous airway lesions (SAL) - 7.5 to 64 %: • other airway malacia [tracheomalacia (TM) and/or bronchomalacia (BM)], • subglottic stenosis • vocal cord paralysis. Self-limiting => supervision by primary care physicians (no need for referral). If severe: surgery (supraglottoplasty) DDx: other causes of stridor = subglottic stenosis, vocal cord paralysis, vascular ring, laryngeal mass (eg, cyst or hemangioma), subglottic hemangioma, and tracheomalacia. b. Tracheomalacia = relatively common anomaly with dynamic collapse of the trachea during breathing => airway obstruction • Most lesions are intrathoracic => airway collapse typically occurs during expiration. • Extrathoracic lesions in the cervical trachea are rare and lead to collapse during inspiration. • Tracheobronchomalacia is the more general term for dynamic collapse of large or smaller conducting airways. Classification: congenital (primary) or acquired (secondary). • Congenital disorders = anything leading to in utero tracheal compression: congenital heart disease with cardiomegaly or intrathoracic masses), craniofacial anomalies and other genetic syndromes, mucopolysaccharidoses, connective tissue diseases, and others. • Acquired causes: chronic barotrauma from positive pressure ventilation, eg, in premature infants with bronchopulmonary dysplasia, infection, or inflammation. Types of tracheomalacia according to underlying pathophysiology: • Acquired defect in the cartilaginous support of the trachea due to prolonged positive pressure ventilation or an infectious/inflammatory process (associates with bronchopulmonary dysplasia/BPD). 32 • Extrinsic tracheal compression by the heart and mediastinal vessels, tumors, lymph nodes, or other masses (congenital or acquired). • Intrinsic defect in the cartilaginous portion of the trachea => increased proportion of membranous trachea with insufficient rigid support => airway collapse. Presentation • Respiratory distress – severity and associated symptoms depend on the location and severity of the tracheal lesion. o Intrathoracic lesions: recurrent harsh, barking, or croup-like cough, as well as stridor and wheezing that improve in supine position and during sleep o Extrathoracic lesions cause inspiratory stridor that improves in supine position and during sleep. o Symptomatic newborns have a greater extent of tracheal collapse. • More severe in tracheobronchomalacia • Associated with protracted bacterial bronchitis, due to ineffective cough and poor mucus clearance caused by tracheal collapse when coughing. Diagnosis: Radiology – little contribution, except dynamic CT/MRI Definitive diagnosis = bronchoscopy during spontaneous breathing Management: remits spontaneously by age of 1 year. Only use respiratory support if severe. Treatment - Wait-and-see - If severe: CPAP, endoscopic stenting, tracheal reconstruction surgery C. Bronchopulmonary dysplasia (BPD) Affects mainly the premature lungs – antenatally and/or postnatally. Definition is based on the need for oxygen supplementation: • if gestational age is < 32 weeks, either at 28 days postnatal age or 36 weeks postmenstrual age (PMA) or discharge home (whichever is first). • if gestational age is 32 weeks or more: >28 days but <56 days postnatal age, or discharge to home, whichever comes first Epidemiology National Institute of Child Health and Human Development (NICHD) statistics for the incidence of BPD for each gestational age (in weeks) using the traditional definition of oxygen supplementation were as follows: ● 22 weeks – 85% ● 23 weeks – 73% ● 24 weeks – 69% ● 25 weeks – 55% 33 ● 26 weeks – 44% ● 27 weeks – 34% ● 28 weeks – 23% Etiology: multifactorial = disruption of lung development and injury due to inflammation and damage caused by: • Antenatal factors (intrauterine growth restriction, maternal smoking) • Postnatal factors (delayed recovery or late deficiency of postnatal surfactant, PDA, mechanical ventilation, oxygen toxicity, and infection) Pathogenesis: • Decreased septation and alveolar hypoplasia => fewer and larger alveoli => reduction in the surface area available for gas exchange. • Dysregulation of pulmonary vasculature development => abnormal distribution of alveolar capillaries and thickening of the muscle layer of the pulmonary arterioles, which results in an increase in pulmonary resistance. o Early disruption of vasculogenesis => pulmonary vascular disease results in pulmonary hypertension => morbidity and mortality. • Increased elastic tissue formation and thickening of the interstitium => compromise septation and capillary development. In one autopsy study, the amount of elastic tissue, septal thickness, and alveolar and duct diameters increased with the severity of BPD Clinical diagnosis: A physiologic test (oxygen reduction test) can be performed to define the actual need for oxygen supplementation to confirm the diagnosis. Infants are classified as 34 having BPD if the oxygen saturation falls below 90 percent within 60 minutes of being placed in room air. Diagnostic criteria 2001 NICHD consensus workshop* [1] Gestational age <32 weeks ≥32 weeks Time point of assessment 36 weeks PMA or discharge to home, whichever comes first >28 days but <56 days postnatal age or discharge to home, whichever comes first Grade Treatment with oxygen >21% for at least 28 days plus Treatment with oxygen >21% for at least 28 days plus Mild BPD Breathing room air at 36 weeks PMA or discharge, whichever comes first Breathing room air by 56 days postnatal age or discharge, whichever comes first Moderate BPD Need* for <30% oxygen at 36 weeks PMA or discharge, whichever comes first Need* for <30% oxygen at 56 days postnatal age or discharge, whichever comes first Severe BPD Need* for ≥30% oxygen and/or positive pressure (PPV or nCPAP) at 36 weeks PMA or discharge, whichever comes first Need* for ≥30% oxygen and/or positive pressure (PPV or nCPAP) at 56 days postnatal age or discharge, whichever comes first Radiology: • Appearance progresses from clear lung fields to diffuse haziness and a coarse interstitial pattern, which reflect atelectasis, inflammation, and/or pulmonary edema. • Lung volumes are normal or low. • With further evolution of the disease, there may be areas of atelectasis that alternate with areas of gas trapping, related to airway obstruction from secretions or bronchiolar injury. • In severe BPD hyperinflation is typical, as well as prominent streaky densities or cystic areas (fibrotic changes). • During acute exacerbations, pulmonary edema may be apparent. Image A is a chest radiograph taken after birth of a premature infant born at 25 weeks. The lungs are clear. Image B is a chest radiograph taken two weeks later, which shows a coarsened interstitial pattern and diffuse haziness. Image C is a radiograph that shows further coarsening of the lung markings five weeks after birth. Image D shows pulmonary congestion after closure of a patent ductus arteriosus (arrow shows clip). Image E is a magnification of image D and shows cystic changes in the lungs (arrows). 35 Associated abnormalities The most serious pathology associated with BPD (from the point of view of morbidity and mortality) is pulmonary hypertension. 36 • • Initial event is the early disruption of angiogenesis => dysmorphic pulmonary vasculature => impaired alveolar development and pulmonary hypertension => explains the between PH and BPD and their shared risk factors (eg, prematurity). Mechanisms that contribute to the development of PH in BPD: o Abnormal pulmonary vascular bed = absolute reduction in size and complexity, increased resting tone of pulmonary artery smooth muscle, and increased reactivity of the arteries to a variety of stimuli. o Oxygen toxicity and ventilator-induced barotrauma and volutrauma – interfere with alveolar development, with reduced numbers of alveoli and intra-acinar arteries => abnormal angiogenesis due to impaired production of nitric oxide and vascular endothelial growth factor, increased expression of endoglin. o Alveolar hypoxia – Paradoxically, chronic/intermittent alveolar hypoxia and acidosis => acute vasoconstriction => further structural change within the affected pulmonary arteries = endothelial cell injury, intimal proliferation, medial hypertrophy, and extension of muscle into the arterial wall. o Cardiac dysfunction – Left ventricular diastolic dysfunction (in systemic hypertension, steroid use), increased left ventricular diastolic pressure, left ventricular inflow obstruction, and left ventricular outflow obstruction. o Pulmonary vein stenosis (PVS) – typically develops after the first few months of life (pathobiology not understood but may be a function of environmental or epigenetic factors) and is associated with high mortality. Terminology Different degrees of prematurity are defined by gestational age (GA), which is calculated from the first day of the mother's last period, or birth weight (BW). Data on BPD are often based upon the following classification of preterm infants who are categorized by their BW or GA: ●Birth weight: •Low birth weight (LBW) − BW less than 2500 g •Very low birth weight (VLBW) − BW less than 1500 g •Extremely low birth weight (ELBW) − BW less than 1000 g ●Gestational age: •Late preterm infants – GA between 34 weeks and <37 weeks •Moderate preterm – GA between 32 weeks and <34 weeks •Very preterm (VPT) infants – GA at or below 32 weeks •Extremely preterm (EPT) – GA less than 28 weeks 37