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Pulmonary agenesis
韶笙: ←Created page with '<!-- EDIT BELOW THIS LINE --><br /> '''Pulmonary agenesis''' is an inborn lung underdevelopment that is rare and potentially lethal<ref name="a" />. The disorder...'
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'''Pulmonary agenesis''' is an inborn lung underdevelopment that is rare and potentially lethal<ref name="a" />. The disorder is caused by a complete developmental arrest of the primitive lung during embryonic life, and it is often associated with other developmental defects<ref name="e" />. Bilateral and unilateral pulmonary agenesis are classified, depending on whether one side of the lung or both sides are affected. Bilateral pulmonary agenesis is lethal, while the mortality rate of unilateral pulmonary agenesis is higher than 50%<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>. Depending on the severity, the symptom ranges from none to various respiratory complaints<ref name="b" />. It is detectable prenatally, however, its nonspecific clinical features act as the obstacle for diagnosing<ref name="e" />. The exact cause of pulmonary agenesis is still obscure. However, theories have been raised regarding the vascular, iatrogenic, viral and genetic causes of pulmonary agenesis in an attempt to explain the pathogenesis of the disorder<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>. In most cases of pulmonary agenesis, surgical resection is performed to remove the malformed lobe or the entire defected lung of the patient depending on the severity of the respiratory impairment<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
[[File:Chest X-ray showing left pulmonary agenesis with mediastinal shift and right lung hyperinflation.png|thumb|Neonatal chest radiograph of a fetus with unilateral pulmonary agenesis]]
== History ==
Pulmonary agenesis was a confusing term before Boyden's classification was published. Before that, the term agenesis was used frequently when reporting cases related to underdeveloped lungs, regardless of the degree of the underdevelopment<ref name="a">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. In 1955, Boyden classified pulmonary agenesis into 3 groups: agenesis, aplasia, and hypoplasia, which has been adopted by most researchers nowadays<ref name="a" />. As a clarification, the term "pulmonary agenesis" in this Wikipedia page will only be referring to the agenesis in Boyden's classification, hence the information contained may not be valid for pulmonary aplasia or hypoplasia unless specifically mentioned. <ref name="b">Liquid error: wrong number of arguments (given 1, expected 2)</ref>
== Signs and Symptoms ==
Pulmonary agenesis is the complete absence of lung tissue, including bronchial tree, lung parenchyma, and supporting vasculatures<ref name="c">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. The only remaining part is rudimentary bronchus<ref name="c" />. Hence, the affected areas lose their function of gas exchange<ref name="c" />. This malformation is thought to involve the proliferation arrest of lung buds during embryo development, while the causes are still debatable. In many cases, it is associated with the occurrence of other inborn malformations<ref name="c" />. The estimated prevalence of pulmonary agenesis is 34/1,000,000 live births, with a slightly higher possibility in the female population. <ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>
Two types of pulmonary agenesis are classified based on the severity of underdevelopment: bilateral and unilateral pulmonary agenesis.
=== Bilateral pulmonary agenesis ===
Bilateral pulmonary agenesis means that both sides of the lung are absent, its occurrence is rare compared to unilateral pulmonary agenesis<ref name="d">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. The fetus losses the ability to do gas change, and is hence incompatible with life after birth<ref name="d" />.
=== Unilateral pulmonary agenesis ===
The severity of unilateral pulmonary agenesis varies depending on the area of tissue affected, being either a single lobe or a whole lung<ref name="b" />.
The clinical features varies in individuals from asymptomatic to various respiratory complaints<ref name="b" />. The occurrences of symptoms also vary from infant stage to childhood, teenager, and adult life<ref name="b" />. Frequently seen clinical features includes [[Dyspnea|dyspnea]], respiratory distress, recurrent pulmonary infections, and limited exercise tolerance<ref name="b" />. Rapid heartbeat, [[Cyanosis|cyanosis]], chest asymmetry, dullness may also be present<ref name="b" />.
Lung function is significantly affected in cases of pulmonary agenesis, demonstrated by reduction in forced expiratory volume and forced vital capacity<ref name="b" />. This reduction in [[Lung volumes|total lung volume]] sets limits on patients' exercise tolerance, and contribute to shortness of breath after exercises<ref name="b" />. The retention of bronchial secretions often leads to recurrent pulmonary infections, adding to damage in lung function, hence causing respiratory stress<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
== Diagnosis ==
The symptoms of pulmonary agenesis are unspecific, and their occurrence varies between individuals<ref name="e">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. These factors increased the difficulty for physicians to diagnose. So, there is a considerable time delay for the disease to be diagnosed, though it's capable of detection since birth or even prenatally<ref name="e" />.
=== Prenatal ===
Prenatal diagnosis of pulmonary agenesis is yet to be reached satisfaction, due to the technical difficulties in differentiating this disorder with other malformation<ref name="e" />. Only a few cases of reported cases are diagnosed before birth<ref name="e" />. [[Biophysical profile|Prenatal sonographic evaluation]], also known as [[Biophysical profile]] is frequently used for prenatal testing. High frequency of associated abnormalities (see the section - "Associated Abnormalities" for details) may also lead to suspicion of pulmonary agenesis<ref name="e" />.
[[Doppler ultrasonography|2‐dimensional color Doppler imaging]] could visually capture the blood flow, hence determine the existence of pulmonary vasculature<ref name="e" />. It is also a frequently used technique for pulmonary agenesis diagnosis<ref name="e" />.
Congenital diaphragmatic hernia (CDH), in this case, the upward displacement of the diaphragm and abdominal organs, is a possible clinical outcome detectable before birth<ref name="c" />. The displacement is caused by organ herniation occupying the empty space in the chest wall, while this space is created by the absence of lung tissue<ref name="c" />. However, it's important to note that a list of other disorders could also be the cause of CDH<ref name="c" />.
=== After birth ===
Several techniques are frequently involved in the diagnosis of pulmonary agenesis after birth.
[[Chest x-ray|Chest X-ray]] is effective in detecting the traits of lung [[herniation]]<ref name="a" />. The unaffected side of lung tends to undergo [[Hypertrophy|hypertrophy]], and move towards the empty space in the chest wall on the opposite side<ref name="a" />. This herniation could be indicated by [[fluoroscopy]]<ref name="a" />. With age increasing, the herniation progresses and ease its detection<ref name="a" />.
Pulmonary [[Angiography|angiography]] assists in detecting the presence of pulmonary artery branches, differentiating pulmonary agenesis to hypoplasia and aplasia<ref name="b" />.
[[Electrocardiography|Electrocardiogram]] is useful in detecting [[Dextrocardia|dextrocardia]], a possible outcome when agenesis is present on the right lung<ref name="a" />. With empty space in the chest wall, the heart rotates in clockwise direction, shifting the location for apex beat occurrence<ref name="a" />. Hence cardiac physical examination also helps as heart sounds is heard best at right chest with [[Dextrocardia|dextrocardia]]<ref name="a" /><ref name="b" />. In the condition of left side agenesis, heart sounds will appear to be louder than normal<ref name="a" /><ref name="b" />.
Chest asymmetry, as a possible trait for pulmonary agenesis, is found to be more obvious in adult patients, especially in males<ref name="b" />. Breast development in females tends to make it less obvious for the observance of asymmetry, though it could still be indicated by a more conical shape and slightly higher location of the breast on the affected side<ref name="b" />.
[[CT scan]], [[Bronchoscopy|bronchoscopy]], [[Bronchography|bronchography]] and [[Magnetic resonance imaging]] also contributes to the observation of patients' lung anatomy<ref name="b" />.
== Causes ==
Although pulmonary agenesis, aplasia and hypoplasia are lethal congenital disorders all resulting from underdevelopment of lungs, pulmonary agenesis and aplasia differ from [[pulmonary hypoplasia]] in their underlying cause<ref name="f">Bradley P. Fuhrman and Jerry J. Zimmerman. (2011). Pediatric Critical Care (4th ed.). p. 599. ISBN 978-0-323-07307-3.</ref>. Unlike [[pulmonary hypoplasia]] which in most cases result from the incomplete development of lung during [[prenatal development]]<ref name="g">Ashcraft, K. W., Holcomb, G. W., Murphy, J. P., & Ostlie, D. J. (2010). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier.</ref>, pulmonary agenesis and [[aplasia]] result from a complete developmental arrest of the primitive lung during [[embryo|embryonic]] life<ref name="f" />.
Whether the [[disorder]] is bilateral or unilateral depends on the stage in which the arrest occurs during the embryonic stage of lung development<ref name="f" />. The earlier the occurrence of developmental arrest, the more severe the defect and the more likely that the agenesis will be bilateral<ref name="f" />. Bilateral pulmonary agenesis is highly rare and it is caused by the complete failure in the development of [[primordium|respiratory primordium]]<ref name="h">Susan E, Wert (2004). Fetal and Neonatal Physiology (3rd ed.).</ref>, the primary structure developed in the earliest stage of embryonic development that gives rise to the entire [[respiratory tract]]<ref>respiratory primordium. (n.d.). Retrieved April 4, 2020, from https://ift.tt/2RjITuK primordium.</ref>. In this case, the absence of lung buds or pleural cavities is observed<ref name="h" />, thus making the case of bilateral pulmonary agenesis highly lethal.
On the other hand, unilateral pulmonary agenesis is caused by the imbalance in the development of [[lung buds]]. Either one side of the lung fails completely, leading to pulmonary aplasia, or one side of the lung is underdeveloped, leading to [[dysplasia]] or [[hypoplasia]]<ref name="h" />. These defects occur during the early stage of lung development, although not as early as bilateral pulmonary agenesis, when [[primordium|respiratory primordium]] bifurcates into right and left primitive [[lung buds]] at the end of the fourth week of [[gestation]]<ref name="h" />.
Although the exact cause of the disorder remains obscure, theories have been advanced throughout history to explain the [[pathogenesis]] of lung agenesis<ref name="i">Fetology: Diagnosis and Management of the Fetal Patient, 2e. (n.d.). Retrieved April 4, 2020, from https://obgyn.mhmedical.com/content.aspx?bookid=1306§ionid</ref>. Based on an [[in vitro]] experiment done in rats, researchers observed lung aplasia in animals that were fed with a diet deficient in [[vitamin A]]<ref>Josef Warkany, Carolyn B. Roth (1948). [[birth defect|Congenital Malformations]] Induced in Rats by Maternal Vitamin A Deficiency: II. Effect of Varying the Preparatory Diet Upon the Yield of Abnormal Young: Four Figures, The Journal of Nutrition, Volume 35, Issue 1, January 1948, Pages 1–11, https://ift.tt/2xZDrq4>. From the result of this experiment, a theory was raised that [[vitamin A deficiency]] during [[pregnancy]] may cause pulmonary agenesis. Some authors have suggested vascular cause of pulmonary agenesis similar to the causes for intestinal atresia<ref name="i" /> and others suggested [[Iatrogenic]] and [[viral]] factors as potential causes of pulmonary agenesis<ref name="i" />. [[Genetic]] cause for pulmonary agenesis has also been raised. It has been said that the gene responsible for the cause of pulmonary agenesis may have variable expressivity and penetrance<ref name="i" />.
==Treatment==
The treatment is dependent on the severity of respiratory impairment and the underlying [[etiology]] of the disorder<ref name="g" />. In most cases, surgical resection is performed to remove the nonfunctioning [[lobe]] or the entire defected lung<ref name="g" />. Removing the malformed part of the lung helps reduce symptoms and chances of [[lung infection]]<ref name="j"><ref>Bradley P. Fuhrman and Jerry J. Zimmerman (2011). Pediatric Critical Care (4th ed.). ISBN 978-0-323-07307-3.</ref>.
In the past, patients underwent [[pneumonolysis|pulmonary plombage]] to render the empty hemithorax<ref name="j">Bradley P. Fuhrman and Jerry J. Zimmerman (2011). Pediatric Critical Care (4th ed.). ISBN 978-0-323-07307-3.</ref>. [[pneumonolysis|Plombage]], also known as [[pneumonolysis|extraperiosteal or extrapleural pneumonolysis]], is a historical treatment procedure for cavity [[tuberculosis]] of upper lobes of lungs used between the 1930s and 1950s<ref name="k">Lee, K. A., Cho, J. Y., Lee, S. M., Jun, J. K., Kang, J., & Seo, J.-W. (2010). Prenatal diagnosis of bilateral pulmonary agenesis: a case report. Retrieved from https://ift.tt/2xRYbzP>. During the operation, a cavity is created by the [[intrathoracic]] placement of inert materials, commonly [[lucite|Lucite (acrylic) balls]], [[ping pong balls]], [[oils]], [[natural rubber|rubber sheets]], [[paraffin wax]], and [[gauze]]<ref name="k" />. As a result, the mediastinal and skeletal shift toward the volume loss side<ref name="g" />.
[[File:Plombage.jpg|none|thumb|258x258px|alt=|Chest radiograph of a 3-year-old who underwent right pulmonary plombage with insertion of three Ping-Pong balls 1 year earlier<ref name="g2">Ashcraft, K. W., Holcomb, G. W., Murphy, J. P., & Ostlie, D. J. (2010). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier.</ref>. ]]
Recent approach involves the implantation of [[tissue expansion|tissue expander]] either via open [[thoracotomy]] or [[thoracotomy|thoracoscopically]] in an attempt to shift the mediastinum back to its anatomical location<ref name="l">Plombage: Radiology Reference Article. (2018). Retrieved April 4, 2020, from https://ift.tt/34j6noN>. Such surgical procedure involving the implantation of [[tissue expansion|tissue expander]] for treating pulmonary agenesis was first reported in Berlin, Germany which was then followed by reports from Bordeaux, France and Verona, Italy<ref name="l" />. The main focus of the treatment procedure is to preserve the remaining functional [[tissue]]<ref name="g" /> and prevent significant [[musculoskeletal disorder|musculoskeletal disfigurement]] that may arise as a side effect of [[tissue expansion|tissue expander implantation]], as the [[mediastinal]] and [[skeletal]] shift towards the volume-loss side<ref name="g" />.
If the defect is extensive but there is a chance for the [[fetus]] to live, an [[EXIT procedure|exo-utero intrapartum treatment (EXIT)]] may be performed to salvage the potential life<ref name="j" />. [[EXIT procedure|EXIT]] technique involves partial delivery of a baby through an [[incision]] in the [[uterus]] while remaining attached to their mother's [[placenta]]<ref name="k" />. Such procedure is necessary for babies who require airway support so that they are provided with a functioning airway before they are detached from their mother's [[placenta]]<ref name="k" />. The [[EXIT procedure|EXIT]] procedure is used to perform [[wedge resection|lung resection]] for babies with extensive lung defects in a relatively stabilized condition after birth<ref>Ex-Utero Intrapartum Treatment: Johns Hopkins Center for Fetal Therapy in Baltimore, Md. (2019, May 7). Retrieved April 4, 2020, from https://ift.tt/2y0yxsw reatment.html</ref>.
==Prognosis==
Prognosis of pulmonary agenesis depends on the degree of pulmonary involvement during the [[embryo|embryonic stage]] of lung development, as well as the patient's history of [[respiratory tract infection|pulmonary infections]] and the presence of associated anomalies<ref name="j" />. The majority of patients diagnosed with bilateral pulmonary agenesis die in [[utero]] or within the first few hours after birth<ref name="m">Sadiqi, J., & Hamidi, H. (2018, October 30). CT features of lung agenesis - a case series (6 cases). Retrieved from https://ift.tt/2RkrGRB>. Numerous cases of bilateral pulmonary agenesis, where both lungs have been affected, have been reported previously<ref name="k" />. On the other hand, the [[hypertrophy]] of the remaining lung to compensate for the lost lung is common in the case of unilateral pulmonary agenesis<ref name="m" />. However, the [[mortality rate]] still exceeds 50%. Most causes of death are because of the presence of associated anomalies and malformations, which are common for pulmonary agenesis especially involving right-sided defects. Those suffering right-sided defects normally have poorer prognosis than those with left-sided defects, partly because the right side of the lung is usually more prone to infection considering the [[standard anatomical position]] of right [[bronchus]], and also because cases with right-sided lung disorders have shown higher association rates with other anomalies<ref name="j" />. In fact, it has been suggested that right-sided defects produce a more severe [[mediastinal shift]], distorting the [[trachea]] and [[great vessels]]<ref name="j" />.
==Associated anomalies==
Considering the fact that a large proportion of mortality cases of pulmonary agenesis are partly due to the presence of associated malformations, it is common to find other [[birth defects|congenital anomalies]] associated with this type of disorder. Although some cases of bilateral pulmonary agenesis were reported as an isolated finding, most cases of pulmonary agenesis are associated with other anomalies, especially in the [[gastrointestinal]], [[genitourinary]] and [[ocular]] systems. Frequently associated congenital anomalies include [[tracheal stenosis]], [[esophageal atresia]], [[tracheoesophageal fistula]], [[bronchogenic cysts]], [[patent ductus arteriosus]], [[tetralogy of Fallot]] and anomalies of the [[great vessels]]<ref name="h" />.
== Reference ==
'''Pulmonary agenesis''' is an inborn lung underdevelopment that is rare and potentially lethal<ref name="a" />. The disorder is caused by a complete developmental arrest of the primitive lung during embryonic life, and it is often associated with other developmental defects<ref name="e" />. Bilateral and unilateral pulmonary agenesis are classified, depending on whether one side of the lung or both sides are affected. Bilateral pulmonary agenesis is lethal, while the mortality rate of unilateral pulmonary agenesis is higher than 50%<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>. Depending on the severity, the symptom ranges from none to various respiratory complaints<ref name="b" />. It is detectable prenatally, however, its nonspecific clinical features act as the obstacle for diagnosing<ref name="e" />. The exact cause of pulmonary agenesis is still obscure. However, theories have been raised regarding the vascular, iatrogenic, viral and genetic causes of pulmonary agenesis in an attempt to explain the pathogenesis of the disorder<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>. In most cases of pulmonary agenesis, surgical resection is performed to remove the malformed lobe or the entire defected lung of the patient depending on the severity of the respiratory impairment<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
[[File:Chest X-ray showing left pulmonary agenesis with mediastinal shift and right lung hyperinflation.png|thumb|Neonatal chest radiograph of a fetus with unilateral pulmonary agenesis]]
== History ==
Pulmonary agenesis was a confusing term before Boyden's classification was published. Before that, the term agenesis was used frequently when reporting cases related to underdeveloped lungs, regardless of the degree of the underdevelopment<ref name="a">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. In 1955, Boyden classified pulmonary agenesis into 3 groups: agenesis, aplasia, and hypoplasia, which has been adopted by most researchers nowadays<ref name="a" />. As a clarification, the term "pulmonary agenesis" in this Wikipedia page will only be referring to the agenesis in Boyden's classification, hence the information contained may not be valid for pulmonary aplasia or hypoplasia unless specifically mentioned. <ref name="b">Liquid error: wrong number of arguments (given 1, expected 2)</ref>
== Signs and Symptoms ==
Pulmonary agenesis is the complete absence of lung tissue, including bronchial tree, lung parenchyma, and supporting vasculatures<ref name="c">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. The only remaining part is rudimentary bronchus<ref name="c" />. Hence, the affected areas lose their function of gas exchange<ref name="c" />. This malformation is thought to involve the proliferation arrest of lung buds during embryo development, while the causes are still debatable. In many cases, it is associated with the occurrence of other inborn malformations<ref name="c" />. The estimated prevalence of pulmonary agenesis is 34/1,000,000 live births, with a slightly higher possibility in the female population. <ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>
Two types of pulmonary agenesis are classified based on the severity of underdevelopment: bilateral and unilateral pulmonary agenesis.
=== Bilateral pulmonary agenesis ===
Bilateral pulmonary agenesis means that both sides of the lung are absent, its occurrence is rare compared to unilateral pulmonary agenesis<ref name="d">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. The fetus losses the ability to do gas change, and is hence incompatible with life after birth<ref name="d" />.
=== Unilateral pulmonary agenesis ===
The severity of unilateral pulmonary agenesis varies depending on the area of tissue affected, being either a single lobe or a whole lung<ref name="b" />.
The clinical features varies in individuals from asymptomatic to various respiratory complaints<ref name="b" />. The occurrences of symptoms also vary from infant stage to childhood, teenager, and adult life<ref name="b" />. Frequently seen clinical features includes [[Dyspnea|dyspnea]], respiratory distress, recurrent pulmonary infections, and limited exercise tolerance<ref name="b" />. Rapid heartbeat, [[Cyanosis|cyanosis]], chest asymmetry, dullness may also be present<ref name="b" />.
Lung function is significantly affected in cases of pulmonary agenesis, demonstrated by reduction in forced expiratory volume and forced vital capacity<ref name="b" />. This reduction in [[Lung volumes|total lung volume]] sets limits on patients' exercise tolerance, and contribute to shortness of breath after exercises<ref name="b" />. The retention of bronchial secretions often leads to recurrent pulmonary infections, adding to damage in lung function, hence causing respiratory stress<ref>Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
== Diagnosis ==
The symptoms of pulmonary agenesis are unspecific, and their occurrence varies between individuals<ref name="e">Liquid error: wrong number of arguments (given 1, expected 2)</ref>. These factors increased the difficulty for physicians to diagnose. So, there is a considerable time delay for the disease to be diagnosed, though it's capable of detection since birth or even prenatally<ref name="e" />.
=== Prenatal ===
Prenatal diagnosis of pulmonary agenesis is yet to be reached satisfaction, due to the technical difficulties in differentiating this disorder with other malformation<ref name="e" />. Only a few cases of reported cases are diagnosed before birth<ref name="e" />. [[Biophysical profile|Prenatal sonographic evaluation]], also known as [[Biophysical profile]] is frequently used for prenatal testing. High frequency of associated abnormalities (see the section - "Associated Abnormalities" for details) may also lead to suspicion of pulmonary agenesis<ref name="e" />.
[[Doppler ultrasonography|2‐dimensional color Doppler imaging]] could visually capture the blood flow, hence determine the existence of pulmonary vasculature<ref name="e" />. It is also a frequently used technique for pulmonary agenesis diagnosis<ref name="e" />.
Congenital diaphragmatic hernia (CDH), in this case, the upward displacement of the diaphragm and abdominal organs, is a possible clinical outcome detectable before birth<ref name="c" />. The displacement is caused by organ herniation occupying the empty space in the chest wall, while this space is created by the absence of lung tissue<ref name="c" />. However, it's important to note that a list of other disorders could also be the cause of CDH<ref name="c" />.
=== After birth ===
Several techniques are frequently involved in the diagnosis of pulmonary agenesis after birth.
[[Chest x-ray|Chest X-ray]] is effective in detecting the traits of lung [[herniation]]<ref name="a" />. The unaffected side of lung tends to undergo [[Hypertrophy|hypertrophy]], and move towards the empty space in the chest wall on the opposite side<ref name="a" />. This herniation could be indicated by [[fluoroscopy]]<ref name="a" />. With age increasing, the herniation progresses and ease its detection<ref name="a" />.
Pulmonary [[Angiography|angiography]] assists in detecting the presence of pulmonary artery branches, differentiating pulmonary agenesis to hypoplasia and aplasia<ref name="b" />.
[[Electrocardiography|Electrocardiogram]] is useful in detecting [[Dextrocardia|dextrocardia]], a possible outcome when agenesis is present on the right lung<ref name="a" />. With empty space in the chest wall, the heart rotates in clockwise direction, shifting the location for apex beat occurrence<ref name="a" />. Hence cardiac physical examination also helps as heart sounds is heard best at right chest with [[Dextrocardia|dextrocardia]]<ref name="a" /><ref name="b" />. In the condition of left side agenesis, heart sounds will appear to be louder than normal<ref name="a" /><ref name="b" />.
Chest asymmetry, as a possible trait for pulmonary agenesis, is found to be more obvious in adult patients, especially in males<ref name="b" />. Breast development in females tends to make it less obvious for the observance of asymmetry, though it could still be indicated by a more conical shape and slightly higher location of the breast on the affected side<ref name="b" />.
[[CT scan]], [[Bronchoscopy|bronchoscopy]], [[Bronchography|bronchography]] and [[Magnetic resonance imaging]] also contributes to the observation of patients' lung anatomy<ref name="b" />.
== Causes ==
Although pulmonary agenesis, aplasia and hypoplasia are lethal congenital disorders all resulting from underdevelopment of lungs, pulmonary agenesis and aplasia differ from [[pulmonary hypoplasia]] in their underlying cause<ref name="f">Bradley P. Fuhrman and Jerry J. Zimmerman. (2011). Pediatric Critical Care (4th ed.). p. 599. ISBN 978-0-323-07307-3.</ref>. Unlike [[pulmonary hypoplasia]] which in most cases result from the incomplete development of lung during [[prenatal development]]<ref name="g">Ashcraft, K. W., Holcomb, G. W., Murphy, J. P., & Ostlie, D. J. (2010). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier.</ref>, pulmonary agenesis and [[aplasia]] result from a complete developmental arrest of the primitive lung during [[embryo|embryonic]] life<ref name="f" />.
Whether the [[disorder]] is bilateral or unilateral depends on the stage in which the arrest occurs during the embryonic stage of lung development<ref name="f" />. The earlier the occurrence of developmental arrest, the more severe the defect and the more likely that the agenesis will be bilateral<ref name="f" />. Bilateral pulmonary agenesis is highly rare and it is caused by the complete failure in the development of [[primordium|respiratory primordium]]<ref name="h">Susan E, Wert (2004). Fetal and Neonatal Physiology (3rd ed.).</ref>, the primary structure developed in the earliest stage of embryonic development that gives rise to the entire [[respiratory tract]]<ref>respiratory primordium. (n.d.). Retrieved April 4, 2020, from https://ift.tt/2RjITuK primordium.</ref>. In this case, the absence of lung buds or pleural cavities is observed<ref name="h" />, thus making the case of bilateral pulmonary agenesis highly lethal.
On the other hand, unilateral pulmonary agenesis is caused by the imbalance in the development of [[lung buds]]. Either one side of the lung fails completely, leading to pulmonary aplasia, or one side of the lung is underdeveloped, leading to [[dysplasia]] or [[hypoplasia]]<ref name="h" />. These defects occur during the early stage of lung development, although not as early as bilateral pulmonary agenesis, when [[primordium|respiratory primordium]] bifurcates into right and left primitive [[lung buds]] at the end of the fourth week of [[gestation]]<ref name="h" />.
Although the exact cause of the disorder remains obscure, theories have been advanced throughout history to explain the [[pathogenesis]] of lung agenesis<ref name="i">Fetology: Diagnosis and Management of the Fetal Patient, 2e. (n.d.). Retrieved April 4, 2020, from https://obgyn.mhmedical.com/content.aspx?bookid=1306§ionid</ref>. Based on an [[in vitro]] experiment done in rats, researchers observed lung aplasia in animals that were fed with a diet deficient in [[vitamin A]]<ref>Josef Warkany, Carolyn B. Roth (1948). [[birth defect|Congenital Malformations]] Induced in Rats by Maternal Vitamin A Deficiency: II. Effect of Varying the Preparatory Diet Upon the Yield of Abnormal Young: Four Figures, The Journal of Nutrition, Volume 35, Issue 1, January 1948, Pages 1–11, https://ift.tt/2xZDrq4>. From the result of this experiment, a theory was raised that [[vitamin A deficiency]] during [[pregnancy]] may cause pulmonary agenesis. Some authors have suggested vascular cause of pulmonary agenesis similar to the causes for intestinal atresia<ref name="i" /> and others suggested [[Iatrogenic]] and [[viral]] factors as potential causes of pulmonary agenesis<ref name="i" />. [[Genetic]] cause for pulmonary agenesis has also been raised. It has been said that the gene responsible for the cause of pulmonary agenesis may have variable expressivity and penetrance<ref name="i" />.
==Treatment==
The treatment is dependent on the severity of respiratory impairment and the underlying [[etiology]] of the disorder<ref name="g" />. In most cases, surgical resection is performed to remove the nonfunctioning [[lobe]] or the entire defected lung<ref name="g" />. Removing the malformed part of the lung helps reduce symptoms and chances of [[lung infection]]<ref name="j"><ref>Bradley P. Fuhrman and Jerry J. Zimmerman (2011). Pediatric Critical Care (4th ed.). ISBN 978-0-323-07307-3.</ref>.
In the past, patients underwent [[pneumonolysis|pulmonary plombage]] to render the empty hemithorax<ref name="j">Bradley P. Fuhrman and Jerry J. Zimmerman (2011). Pediatric Critical Care (4th ed.). ISBN 978-0-323-07307-3.</ref>. [[pneumonolysis|Plombage]], also known as [[pneumonolysis|extraperiosteal or extrapleural pneumonolysis]], is a historical treatment procedure for cavity [[tuberculosis]] of upper lobes of lungs used between the 1930s and 1950s<ref name="k">Lee, K. A., Cho, J. Y., Lee, S. M., Jun, J. K., Kang, J., & Seo, J.-W. (2010). Prenatal diagnosis of bilateral pulmonary agenesis: a case report. Retrieved from https://ift.tt/2xRYbzP>. During the operation, a cavity is created by the [[intrathoracic]] placement of inert materials, commonly [[lucite|Lucite (acrylic) balls]], [[ping pong balls]], [[oils]], [[natural rubber|rubber sheets]], [[paraffin wax]], and [[gauze]]<ref name="k" />. As a result, the mediastinal and skeletal shift toward the volume loss side<ref name="g" />.
[[File:Plombage.jpg|none|thumb|258x258px|alt=|Chest radiograph of a 3-year-old who underwent right pulmonary plombage with insertion of three Ping-Pong balls 1 year earlier<ref name="g2">Ashcraft, K. W., Holcomb, G. W., Murphy, J. P., & Ostlie, D. J. (2010). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier.</ref>. ]]
Recent approach involves the implantation of [[tissue expansion|tissue expander]] either via open [[thoracotomy]] or [[thoracotomy|thoracoscopically]] in an attempt to shift the mediastinum back to its anatomical location<ref name="l">Plombage: Radiology Reference Article. (2018). Retrieved April 4, 2020, from https://ift.tt/34j6noN>. Such surgical procedure involving the implantation of [[tissue expansion|tissue expander]] for treating pulmonary agenesis was first reported in Berlin, Germany which was then followed by reports from Bordeaux, France and Verona, Italy<ref name="l" />. The main focus of the treatment procedure is to preserve the remaining functional [[tissue]]<ref name="g" /> and prevent significant [[musculoskeletal disorder|musculoskeletal disfigurement]] that may arise as a side effect of [[tissue expansion|tissue expander implantation]], as the [[mediastinal]] and [[skeletal]] shift towards the volume-loss side<ref name="g" />.
If the defect is extensive but there is a chance for the [[fetus]] to live, an [[EXIT procedure|exo-utero intrapartum treatment (EXIT)]] may be performed to salvage the potential life<ref name="j" />. [[EXIT procedure|EXIT]] technique involves partial delivery of a baby through an [[incision]] in the [[uterus]] while remaining attached to their mother's [[placenta]]<ref name="k" />. Such procedure is necessary for babies who require airway support so that they are provided with a functioning airway before they are detached from their mother's [[placenta]]<ref name="k" />. The [[EXIT procedure|EXIT]] procedure is used to perform [[wedge resection|lung resection]] for babies with extensive lung defects in a relatively stabilized condition after birth<ref>Ex-Utero Intrapartum Treatment: Johns Hopkins Center for Fetal Therapy in Baltimore, Md. (2019, May 7). Retrieved April 4, 2020, from https://ift.tt/2y0yxsw reatment.html</ref>.
==Prognosis==
Prognosis of pulmonary agenesis depends on the degree of pulmonary involvement during the [[embryo|embryonic stage]] of lung development, as well as the patient's history of [[respiratory tract infection|pulmonary infections]] and the presence of associated anomalies<ref name="j" />. The majority of patients diagnosed with bilateral pulmonary agenesis die in [[utero]] or within the first few hours after birth<ref name="m">Sadiqi, J., & Hamidi, H. (2018, October 30). CT features of lung agenesis - a case series (6 cases). Retrieved from https://ift.tt/2RkrGRB>. Numerous cases of bilateral pulmonary agenesis, where both lungs have been affected, have been reported previously<ref name="k" />. On the other hand, the [[hypertrophy]] of the remaining lung to compensate for the lost lung is common in the case of unilateral pulmonary agenesis<ref name="m" />. However, the [[mortality rate]] still exceeds 50%. Most causes of death are because of the presence of associated anomalies and malformations, which are common for pulmonary agenesis especially involving right-sided defects. Those suffering right-sided defects normally have poorer prognosis than those with left-sided defects, partly because the right side of the lung is usually more prone to infection considering the [[standard anatomical position]] of right [[bronchus]], and also because cases with right-sided lung disorders have shown higher association rates with other anomalies<ref name="j" />. In fact, it has been suggested that right-sided defects produce a more severe [[mediastinal shift]], distorting the [[trachea]] and [[great vessels]]<ref name="j" />.
==Associated anomalies==
Considering the fact that a large proportion of mortality cases of pulmonary agenesis are partly due to the presence of associated malformations, it is common to find other [[birth defects|congenital anomalies]] associated with this type of disorder. Although some cases of bilateral pulmonary agenesis were reported as an isolated finding, most cases of pulmonary agenesis are associated with other anomalies, especially in the [[gastrointestinal]], [[genitourinary]] and [[ocular]] systems. Frequently associated congenital anomalies include [[tracheal stenosis]], [[esophageal atresia]], [[tracheoesophageal fistula]], [[bronchogenic cysts]], [[patent ductus arteriosus]], [[tetralogy of Fallot]] and anomalies of the [[great vessels]]<ref name="h" />.
== Reference ==
April 27, 2020 at 11:59PM
