Tetralogy of fallot

First anatomic descriptionDanish anatomist Niels Stensen, in 1672... Described in detail by fallot in 1888la maladie bleue
Tetralogy of fallot with pulmonary atresia10% Rarer variants include tetralogy of fallot with absent (or dysplastic) pulmonary valve and tetralogy of fallot with common atrioventricular canal[<5%]

 Prevalence 0.26 to 0.48 per 1,000 live births In about 70% of tetralogy of Fallot patients, a putative genetic etiology remains to be determined. Genes identified : NKX2.5, [4%]; JAG1 in Alagille syndrome.; TBX5 in Holt-Oram syndrome. Sibling recurrence rate 2.5% to 3% if only one sibling is affectedlikely to increase substantially if more than one sibling is affected.

Environmental factors maternal diabetes [threefold increased risk], retinoic acids, maternal phenylketonuria (PKU), and trimethadione

Genetic cause : heterogeneous

 Syndromes and associations.. DiGeorge/Velocardiofacial syndrome, Down syndrome, Alagille syndrome, cat's-eye syndrome, recombinant chromosome (or San Luis Valley) and Kabuki syndromes, and CHARGE and VATER/VACTERL associations. Microdeletion on 22q11.seen in 1535% of TOF patients; 45% of TOF + PA; 65% of those with TOF + APV.

Developmental FAULT Defective embryonic neural crest migration abnormal conotruncal development. Incomplete rotation and faulty partitioning of the conotruncus during septation. Malrotation of truncal-bulbar ridges results in misalignment of the outlet and trabecular septum and consequent straddling of the aorta over the malaligned VSD. Abnormally anterior septation of the conotruncus by the bulbotruncal ridgessubpulmonic obstruction

 Tetrad right ventricular outflow obstruction, aortic override, ventricular septal defect, and right ventricular hypertrophy

PS

Most characteristic . subpulmonic stenosis Obstruction along the entire course of the RVOT and pulmonary arteries (LPA commonly) can occur. In general, the more severe the proximal obstruction, the greater the likelihood of distal areas of obstruction Obstruction within the RV body : 1)hypertrophy of the septoparietal muscle bundles ; 2)anatomic displacement of the normal moderator band attachment

Pulm valve.bicuspid in 40% VSD : nonrestrictive..Few ptsVSD restrictive d/t the accessory TV prolapsing thru the defect

Coronary Anomalies

LAD from RCA (5%) & coursing in front of infund (Sx imp) Single coronary (4%) So coronary evaluation before Sx imp Echo.proximal coronary If needed root angio / CAG.. MRI/CT

LAD
Pulm. Valve RCC
PA
RCA
LAA

RCA

AO
LCX

MPA

NCC

LCx

LAD

 Right Aortic A in 25%......Twice more common in TOF+PA Aortopulmonary Collateral Arteries..MC with TOF + PAOnly type 1, or bronchial artery collaterals, were documented in TOF with PS.: Stenosis of LPA in 40% Associated cardiac abnormalities PFO or a true atrial defect in 83% of hearts with TOF AVSD (downs)LSVC(11%) Left heart lesions are rareAortic valve disease may be acquired as a result of surgical trauma, progressive root dilation, or 20 to endocarditis. TOF with Absence of PAalmost always LPA.PS murmur radiates to Rt chestCXR..Lt hemithorax small,Lt lung hypovasc,Lt hemidiaphragm elevated

Morphology of Pulmonary Arterial Supply 3 major patterns : (1)most favourable R/L PA are confluent, and are supplied by an arterial duct [unifocal] (2)the intrapericardial pulmonary arteries are confluent, but co-exist with systemic to pulmonary CAs. (3)absence of the intrapericardial pulmonary arteries.so fully supplied by multiple systemic-to-pulmonary CAs.

 Unifocal.. usually the persistently patent arterial duct; rarely solitary systemic-to-pulmonary collateral artery/AP window/fistula from the coronary arteries. Multifocal :MAPCAs: typically 2-6 in number; usually arise from the anterior wall of the aorta opposite the origin of the intercostal arteries. It is a rule that an arterial duct will not be present when a lung is supplied by systemic to pulmonary CAs. The key to complete clinical diagnosis is to establish the course of each artery, to establish whether it runs directly into the lung or makes connections with intrapericardial and central pulmonary arteries, and to identify with precision the sites of these anastomoses.
Acquired CAs[TOF with PA] . join the pulmonary circulation at immediately precapillary level.

 APCs the Rt upper artery supplies exclusively the RUL in direct fashionRt lower artery feeds the middle and lower lobes of the Rt lung through an anastomosis with the intrapericardial arterial tree, shown in blue, at hilar level.Left sideCAs are shown feeding the Lt lung through anastomoses at segmental level.

(1)Absent intrapericardial PAs

(2) Anastomoses between the CAs and the intrapericardial PAs (extrapulm,hilar,lobar,segmental)

Pathophysiology and Hemodynamics

Severe cyanosis in profound RL shunting, Some pts have a net LRshunt. Hemodynamic featuresRV hypertension because of the large VSD, with normal or low PAP.The low distal PAP is maintained as a result of the various levels of pulmonic obstruction. The PVR in the distal pulmonary arterial bed is usually normal.
The extent and direction of shunting .determined by the cumulative amount of obstruction to PBF(Subpulmonic obstruction in all; obstruction @ valvular, supravalvular, and branch arteries are also common).

 Balance between PBF & aortic BF will be determined by the difference in impedance between the unobstructed ,highresistance systemic vascular bed and the obstructed pulmonary outflow tract and vascular bed. RVH in proportion to LV mass in nonrestrictive VSD. In restrictive VSD(suprasyst RVP)..severe RVH Obstruction to PBF is relatively fixed & variation in cyanosis is determined by the changing SVR Hypercyanotic episodethought to result from an acute increase in infundibular obstruction and a proportional decrease in PBF.

C/F : Wide due to variable severity of RV outflow obstruction USGfetal diagnosis Newborn & infantscyanosis; systolic murmur Acyanotic TOFmild pulmonary overcirculation rarely CHF unless there is a large PDA or aortopulmonary collateral arteries Pregnancypoorly tolerated gest decrease in SVR increases R-L shunt & the labile SVR during labor,delivery leads to abrupt hypoxemia..high fetal wastage / dysmature offspring

HYPERCYANOTIC SPELLS OR TETRALOGY SPELLS :

best described in TOF;can occur with other forms of structural heart disease. mediated, in part, by dynamic changes (acute increase)in subpulmonic obstruction.. changes in contractility due to endogenous catecholamines or exacerbated by hypovolemia other mechanisms[pulmonary atresia and VSD] . decrease in systemic vascular resistance. Child may assume squatting posture (instinctive) during spells Pathogenetic mechanisms : Vulnerable respiratory control centres ;Increase in HR ; Increase in CO & VR ;Increase in R L shunt; Infundibular contraction may reinforce,but does not initiate

TYPICAL SPELL : The child becomes distressed and inconsolable, without apparent reason, most often in the morning. Peak incidence2nd-6th m ;few after 2 yrs Crying is associated with progressively deeper cyanosis and hyperpnea (not tachypnea). Spells are self-aggravating; During the spell diminished/absent murmur Not infrequently,the spell terminates with unconsciousness and, rarely,convulsions. If the hypoxemia is extreme, permanent neurologic sequelae and even death may ensue. True hypercyanotic spells are rare in neonates, although cyanosis may increase with crying.

O/E : o cyanosis ; clubbing ; o Arterial pulses normal in uncomplicated TOF; o Wide pulse pressure (arterial diastolic runoff). aortopulmonary collaterals, palliative surgical shunt or PDA; o Accentuated precordial RV impulse; o LV impulse will not be hyperactive (normal cardiac output); o S2 single& loud (anterior, dextroposed aorta); o S3/S4 are unusual; o Aortic ejection click; o Systolic murmurcrescendo-decrescendo @ LUSB. The intensity of the murmur inversely parallels the degree of pulmonic obstruction; o Diastolic murmurs are unusual..Rarely AR murmur; o TOF with PA..no harsh, obstructive precordial murmurs; o A harsh diastolic murmur, with a harsh murmur of PS, [harsh sawing, to-and-fro murmur ] TOF and APV syndrome; o Continuous murmurs.PDA;aortopulmonary collaterals ;may be best heard in the back.

ECG QRS axis same as that of a normal newborn RVHTall monophasic R in V1 with an abrupt change to an rS pattern in V2 (Tall R extends into adj precordial leads in TOF + APV) Reduced PBF+ underfilled LVrS in V2-V6 Balanced shunt qR in V5,V6 L-R shuntQR in V5,V6 LAD with counterclockwise depolarisn TOF+AVSD

CXR:

Normal sized heart; [may be large in PA] upturned apex; attenuated & concave left heart border (infundibular and PA hypoplasia).boot-shaped heart, or coeur en sabotsmall underfilled LV that lies above horiz IVS, inferior to which is a concentric hypertrophied nondilated RV Diminished pulmonary vascularity in proportion to the degree of cyanosis. Absent thymic shadow in the newborn may indicate associated chromosome 22q11.2 microdeletion (DiGeorge syndrome). RAA in roughly 25%...accompanied by Rt DA on Rt side In PA..lacy reticular pattern (d/t the anast b/w lobar/segm PAs & CAs) Syst arterial collaterals rarely cause rib notching as they do not run in intercostal grooves.

ECHO : PLAX :

VSD; degree of aortic override; ?bilateral conus; AR; Doppler low velocity R-L shunt; dilated CS..?LSVC; Absent DA..R/O RAA Cranial tilt of the transducer..infundibulum and the proximal pulmonary arteries. [location and degree of infundibular, valvular, and arterial hypoplasia] Basal SAX: RVOT and proximal pulmonary arteriesdegree of PS.PDA? VSD [just below the RCC, or at 10 o'clock position]. Tricuspid-aortic continuity confirms the perimembranous nature. Coronariesorigin and course echo showed sensitivity of 82%, specificity of 99%, and accuracy of 98.5% in a study by Need et al high parasternal and suprasternal views will provide visualization of the pulmonary arteries and aorta, respectively

LAD
Pulm. Valve
RCC NCC
MPA

RCA

LCx

The anomalous LAD crossing the RVOT in TOF is identified when the transducer is swept superiorly in the parasternal short -axis view . This allows visualization of the anomalous LAD that is situated anterior to the RVOT

RCA
Pulm valve

Ao
LAA

Ao

Here a normal LAD (arising from the LCA and coursing posterior to the pulmonary valve) and a normal RCA are shown in the top frames for comparison.

64-slice HRCT : Questions about preoperative pulmonary artery anatomy, coronary artery anatomy, and systemic or pulmonary venous anatomy can frequently be resolved even in newborns with 64-slice high-resolution CT scans. CMR : Assessment of pulmonary anatomy Postoperative assessment of RV function, myocardial scarring, and PR fraction

Cardiac Catheterization Less often needed ; Diagnostic Therapeutic foremost goal . clarification or better definition of anatomic characteristics, such as pulmonary arterial or coronary arterial anatomy coronary artery anatomy either by aortic root angio, selective coronary artery injection, or a combination of both. Definition of any aortopulmonary collaterals .usually originate from the descending aorta.

MANAGEMENT

Medical Management ductal-dependent pulmonary blood flow ?......neonates with critically restricted antegrade blood flow need to be started on prostaglandin E1and considered for either total repair or a systemic-to-pulmonary shunt. Most newborns with TOF do not have ductal-dependent pulmonary blood flow and may be followed without specific early intervention. Parental education for recognition of cyanotic spells [even acyanotic TOF are at risk for the development of spells in the first months of life]. IE Prophylaxis for cyanotic/palliated patients ; patients for 6 months after patch repair surgery, and those with prosthetic valves

Hypercyanotic spells Rx aims @ lowering impedance to pulmonary flow and further increasing systemic vascular resistance. Rx..oxygen, volume expansion, sedation with morphine or ketamine, and, if needed, vasopressors[phenylephrine] Refractory to above .. Transfusion of whole blood/red cells Balloon angioplasty of pulm annulus Emergent surgical palliation or repair Propranolol having some efficacy in minimizing or extinguishing the occurrence of spells. It may be used for patients who are awaiting surgical intervention or who have a medical contraindication to either complete repair or aortopulmonary shunt.

 Infants with very severe RVOT stenosis and those with TOF + PA,with SaO2<70%, should have surgery within a few weeks after birth. Infants with moderately severe stenosis and marked cyanosis (SaO2 7090%) should have corrective surgery by 24 months. Corrective surgery should be performed in all other infants with tetralogy of Fallot by 6 months.
Contraindications for repair in early infancyPalliation initially LAD from RCA crossing infundibulum Severely hypoplastic PAs Pulmonary atresia

Palliative Procedures

Classic BT shunt[1945]SCAPA on side opposite AA Modified BT esp in small infants <6 monthsside to side anastom with interposition graft of PTFE or Gore-Tex b/w SCA & PA [on the same side of AA]
Waterston shunt : Side-side anastomosis of RPA to AA Potts : Side - side anastomosis of LPA to DA Waterston/Potts shunts : complications Excessive PBF HF [20%] & PHTN Difficulty taking shunt down at time of correction Distortion of Rt/Lt PA ; Right/Left PA aneurysm

BT shunt-advantages : (a)low incidence of problems from excess PBF (b)No pericardial adhesions as pericardium is not entered (c)Easy to close @ time of complete repair..ligating its distal part just proximal to anastom with PA (d)Less distortion of PAs CENTRAL SHUNT :connecting a short tubular graft of Teon or GoreTex from the aorta to the MPA. advantages vs other shunts: the size of the communication could be controlled by selecting a tube with a diameter appropriate for the patient; branch PAs are not disturbed so that reconstruction is not required at the time of corrective surgery.

CLASSIC BT shunt

POTTS SHUNT

WATERSTON SHUNT

Interventional procedures : In patients with severe annular hypoplasia.. palliation of significant cyanosis by balloon valvuloplasty or RVOT stent placement can be done Improvement in antegrade flow is thought to simultaneously enhance pulmonary arterial growth by augmenting PBF Balloon angioplasty of the pulmonary valve annulus is preferable to a shunt procedure as it is less traumatic, it avoids a thoracotomy, reduces the likelihood of distortion of the pulmonary arteries Coil embolization of APCs .Coiling of vessels that perfuse pulmonary segments already supplied by pulmonary arterial flow serves to reduce LV volume loading as well as to eliminate runoff into the pulmonary arterial bed during CPB

Surgery aims @ relieving all possible sources of RVOTO; If possible, pulmonary valve function is preserved by avoiding a transannular patch Closure of VSD (dacron patch) To relieve RVOTOpulmonary valvotomy, the insertion of an outflow tract patch or a transannular patch are often required. Surgery during early infancy, when the pulmonary annulus is markedly stenotic, frequently requires the insertion of a long and wide transannular patch.

Consequently, most patients acquire PR as a result of the repair. PR may be well tolerated by many in the early postoperative years, but in the long term chronic PR is associated with reduced exercise capacity, RV dilatation, ventricular arrhythmias, and sudden death.

PVR : Early PVR in selected patients results in beneficial remodelling of the right ventricle Optimal timing is critical for preserving RV function (not too late) and avoiding the need for early re-operation (not too early). Amelioration of RV function following PVR has to be weighed against the risk of subsequent re-operation for homograft failure. StudiesRV end-diastolic volume may become a helpful indicator for defining both a lower limit (150mL/m2) and an upper limit for re-intervention (200mL/m2).[normal 60100] CMR is the gold standard for evaluation of RV volumes and quantification of the degree of PR & TR.

SURGERY in TOF contd VSD closure : Done thru RA approach whether or not a transannular patch is used, as this approach allows to minimise the length of the right ventriculotomy (length only necessary to relieve the RVOT obstruction and not for the VSD exposure). Efficacy of the RA approach . Preserves the right ventricular function, .. Resultant PR after limited transannular patching is less severe than that which occurs after transventricular repair Less incidence of ventricular/atrial arrhythmias is Easier to preserve the integrity & function of the tricuspid valve.

Concerns of right ventriculotomy (classical RV approach) Low cardiac output in the early postoperative period, a higher incidence of arrhythmias, Risk of late sudden death

In case of a major coronary artery crossing the RVOTan external conduit or homograft would be necessary; Risk factors for early death after repair: 1) very young age 2) older age 3) severity of annular hypoplasia 4) small size of pulmonary arteries 5) need for transannular patch (debatable) 6) high peak RV to LV pressure ratio 7) previous palliative operations 8) multiple VSDs 9) co-existing cardiac anomalies

Advantages of early total correction Prevents cerebral hypoxia,cerebral embolism, abscess and hematological changes Decrease RVPprevent persistent myocardial hypertrophy and probably reduce the risk of brosis of the RV Providing adequate PBF will optimize the opportunity for normal growth of the main and branch PAsalso normal pulmonary circulation may be important for lung development. Tendency for progressive hypertrophy of the RV infundibular region is largely abolished by early repair. Early separation of MAPCAs from aorta reduces the risk of PVOD

SURGERY IN TOF + PA : PA anatomy not favourable? .Palliative procedures Central shunt vs reconstruction of RVOT using a patch/conduit while leaving open the VSD If PA anatomy appears amenable to reconstruction, procedures leading to complete repair are indicated. Such procedures include RV outflow reconstruction for inducement of central pulmonary artery growth using a valved conduit / aortic or pulmonary homograft If there is a connection between RV & PT correction can be achieved with a patch reconstruction

PA anatomy assessment

1) McGoon ratio: (Diameter of RPA/DAo + Diameter of LPA/DAo)

Normal 2.1 Adequate for VSD closure 1.2 Inadequate <0.8 for VSD closure

2) Nakata Index:(CSA of RPA + CSA of LPA)/BSA Normal value > 200 mm2/m2 > 150 mm2/m2 is adequate. (Not usable preoperatively when MAPCAs are the major source of PBF & one-stage unifocalization + full repair is planned).

3) Total Neo-Pulmonary Artery Index (TNPAI) = APC index + Nakata Index APC index is the sum of CSA of all usable APCs/BSA >250 - suitable for one-stage repair including VSD closure (These pts. have low RV/LV pressure ratio postoperatively).

Critique of all these indices: These indices consider only the size of proximal vessel and not consider the condition of distal parts of the vessels (which may be stenosed). Recently the value of all these has been questioned

MAPCAs : management : 2 options 1)Obliterate them by Sx ligation/coil embolisation 2)Surgical unifocalisation : if it is the sole supply to many segments ..connecting all MAPCAs, as well as the small native pulmonary arteries, to one source of blood ow from the RV [ie to a central PA confluence or prosthetic PA confluence].. If performed early,it avoids the dvpt of PVOD changes, as well as stenoses in the MAPCAs. If the pulmonary vascular morphology and resistance are such that adequate PBF can be accommodatedthen RVP after correction will be low enough to close the VSD.

 To assess whether this is likely, surgeons at the University of California in San Francisco perfuse blood from the perfusion system through the pulmonary artery at a rate of 2.5 L/min per m. If PA mean pressure is <25 mmHg, it is considered safe to close the VSD. If it is not closed, the patient is followed; the PVR may decrease over time, allowing later closure. Also, if stenoses in pulmonary vessels are noted, relief by balloon angioplasty, with stenting if necessary, may permit RVP to fall and permit closure of the defect.

Post surgery if the RVP/LVP is >0.75.RVF may resultavoid closure VSD / fenestrated patch closure

Hypoplastic PAs intervene early . Encourage them to grow Reconstruction of RVOT with a patch or valveless conduit Placement of a central AP shunt If MPA,RPA & LPA are present, even though very small (diameter 3 mm), they are capable of considerable enlargement if blood ow through them is increased. Creating an AP window early in infancy sufcient enlargement of the pulmonary arterial tree to later perform successful repair using the normal pulmonary arteries and a unifocalization procedure can be avoided.

Dvpt of small pulmonary arteries (A) Before central shunt was performed, the Nakata index was 64 and the McGoon ratio was 0.82. (B) One hundred seventyfour days after operation, the Nakata index rose to 89 and the McGoon ratio to 1.1.

Post Repair for TOF in general Current surgical survival, even for symptomatic infants <3 months of age, is excellent. Hospital and 1-month survival rates of 100% have been reported. Earlier age at repair (<1 year of age) did not adversely affect the rate of reintervention; so primary repair should be regarded as the preferred management strategy. Twenty-year survival for hospital survivors, irrespective of management strategy, was 98% for patients who have TOF with PS and slightly lower for patients with PA, reflecting the overall excellent long-term survival of these patients.

COURSE In unrepaired TOF.increasing cyanosis due to progressive infundibular obstruction. Beyond the neonatal period, they are also at increasing risk for developing hypercyanotic spells. Older children with unrepaired or palliated TOF complications a/w chronic cyanosis ,polycythemiastroke, brain abscess, and pigment gallstones. Now rare infant repair is the rule PVOD in TOF : rare large surgical systemic-to-pulmonary artery shunts persisting large aortopulmonary collaterals

REPAIRED TOF :

Outcomes : excellentrecent reportsmortality <3%

Problems that may develop include a)Residual VSDs

Persistent defects at the patch margin or Previously unrecognized or underestimated additional defects in the muscular septum. Partial patch dehiscence

b)Recurrent RVOTO :

Muscle bundles obstruct the os infundibulum in 3% Nontransannular patchesannulus becomes restrictive as child grows Transannular patchrestriction at the distal insertion of the patch into the branch pulmonary arteries. Stenosis owing to compression from an aneurysmal RVOT patch . should be approached surgically with revision of the patch and repair of the proximal obstruction. may dvp additional sites of peripheral PS over time.

c)Progressive aortic root dilation &AR :

Intrinsic dvptal abnormalities of aortic valve/root Palliative shunts or significant APCs left-to-right shunt volume contribute to aortic dilation. Progressive dilation of aorta correlate with longer time between palliation & repair ; Pulmonary atresia ; right AA & male gender.

d) RV dilation;syst/diast dysfunction later RHF

excess volume load from pulmonary regurgitation pressure load from outflow obstruction, Hypoxemic coronary perfusion, surgical incision, patch and scarring, and post cardiopulmonary bypass ischemia reperfusion injurypossibly superimposed on tetralogy associated congenital abnormalities of the myocardium.

e) LV dysfunction consequence of adverse ventricular

interaction. f) Rhythm disturb./SCD : Long-term mortality . 3% to 6%. A review of 125 adult patients with TOF suggested that a greater degree of PR, a history of sustained VT, QRS duration >180 ms, or LV dysfunction was a predictor of sudden death g) Lower IQ h) Life time increased risk for IE i)Membranous subaortic stenosis ..may be seen years after the initial repair in a few patientsmay require surgical excision. j)Small coronary-to-RV fistulas, thought to relate to the excision of muscle in the right ventricular outflow tract.

Post repair TOF + PA : Need for reoperation/ transcatheter balloon dilation and stenting of an obstructed conduit in RV to PA conduit surgery patients. Ongoing risk for recurrent peripheral PSserial catheterizations are indicated for ongoing pulmonary artery rehabilitation higher risk for progressive aortic root dilation and AR

TOF + AVCD : risk for atrioventricular valve incompetence . TR right ventricular dilation, and dysfunction.

Congenital Absence of Pulmonary Valve Syndrome

Chever in 1847 incompletely formed, rudimentary pulmonary valve that typically is both stenotic and regurgitant ; aneurysmally dilated PA, and a large malaligned outlet VSD. PDA is always absent.has been postulated as being responsible for its pathogenesis and PA dysplasia. Other clinical features fairly typical in this disorder include the common association of airway abnormalities that may lead to severe respiratory failure . The conal septal abnormalities and infundibular obstruction, however, in distinction to typical tetralogy, are less severe or absent, and much of the PS results from annular hypoplasia.

 Typically present in the neonatal period, and are diagnosed based on the presence of their characteristic murmur and the presence of cyanosis. A significant proportion of patients will present with associated respiratory distress or frank respiratory failure, often requiring mechanical ventilation. harsh to-and-fro murmur of PS followed by the diastolic murmur of PR.sound of sawing wood CXRMassively dilated Pas ; Infundibular dilation project leftward as a hump shaped shadow ; Pulmonary vascularity is normal

 Some neonates present with severe bronchial obstruction and require immediate tracheal intubation and mechanical ventilation, followed by early surgical repair. Moderate resp obstruction lying prone may help by relieving the anterior vascular compression of bronchi Mild or no airway obstruction may require no additional support in the neonatal period and go on to elective repair later in infancy. The surgical repair.. in addition to ventricular septal defect closure and right ventricular outflow reconstruction, involves reduction of the aneurysmal mediastinal pulmonary arteries to relieve bronchial compression.

Outcome of TOF + APV depends largely on the severity of airway disease. Even after Sx,some pts continue to have bronchial obstruction Residual airway hypoplasia and deformity Abnormally branching segmental pulmonary arteries compressing the intraparenchymal bronchi As these patients grow, however, pulmonary function tends generally to improve as PAP fall and the maturing tracheobronchial tree develops less compressible walls and larger caliber.

THANK YOU