Foreign body aspiration

Foreign body aspiration is when an object is inhaled and becomes lodged in a child’s airway or lungs. Foreign body aspiration remains a significant cause of death in children for anatomic as well as developmental reasons ¹. Foreign body aspiration is the number one cause of accidental infantile deaths ² and the fourth leading cause of death in preschool and younger age children less than five years of age ³. Foreign body aspiration accounts for a significant number of emergency department visits in the United States. The position of a child’s larynx or voice box, also makes small children susceptible to aspiration of foreign bodies into the airway. It’s natural for children to explore their environment by seeing, touching and tasting objects around them. Unfortunately, their tendency to put non-food objects in their mouth can be dangerous or even life threatening.

Children can also choke on foods given to them too early in their development, before they have the molars and coordinated chewing motions to safely break those foods down. Because infants and young children aged 6 months to 3 years lack molar teeth, have uncoordinated swallowing mechanisms, and, most importantly, engage with their surroundings by placing objects in their mouths, they are prone to foreign body aspiration ⁴.

Choking is typically defined as an aerodigestive foreign body causing varying amounts of obstruction to the airway. The obstruction can lead to difficulties with ventilation and oxygenation thus resulting in significant morbidity or mortality. The most commonly aspirated foreign bodies in children include vegetable matter, nuts and round foods such as hot dogs and grapes, coins, toys, and balloons. Less common, but more difficult to manage foreign bodies include beads, pins and small plastic toys, among an infinite number of other small objects. Aspirate objects, most commonly peanuts, lodge with the highest frequency within the right main stem bronchus due to its larger size and more vertical alignment as compared with the left. The main cause of death has been attributed to hypoxic-ischemic brain injury and less commonly, pulmonary hemorrhage ⁵.

According to the National Safety Council, in 2016 the rate of fatal choking in American children <5 years of age in the general population was 0.43 per 100,000. However, a previous study analyzing non-fatal choking data of children under the age of 14 has revealed a comparatively higher rate of 20.4 per 100,000 population. 55.2% of these non-fatal choking cases in children <4 years of age involved candy, with hot dogs and nuts being more likely to require hospitalization. Males accounted for 55.4% of cases but there was no statistically significant difference between the sexes. Analysis of the national trend of inorganic foreign body aspiration has revealed that aspirated coins have decreased in relative frequency with aspirated jewelry conversely becoming more common in the United States. Overall the rate of aspiration from foreign bodies resulting in emergency department visits has remained stable between the years of 2001 and 2014.

A recent meta-analysis of the worldwide literature on foreign body aspiration revealed a sex discrepancy with 60% of patients being males. Nuts were seen to be causative in 40% of cases in high-income and low-middle income nations. Among inorganic foreign bodies, a pooled proportion among the literature stemming from high-income countries revealed that magnets were causative in 34% of the cases. Diagnosis was delayed by more than 24 hours in 60% of those particular cases ⁶.

Often, diagnosing and treating foreign body aspiration requires special expertise and equipment.

Chest radiography is the first-line imaging study in cases of suspected foreign body aspiration because it is readily available, low in cost, and associated with minimal radiation exposure ⁷. As only 10% of aspirated foreign bodies are radiopaque ⁸, however, indirect signs of aspiration including air trapping, focal airspace disease, pleural effusion, mediastinal shift, pneumothorax, or subcutaneous emphysema are important imaging surrogates. Unilateral hyperinflation ⁹ is the most commonly identified indirect sign of aspiration (Figure 3a) ¹⁰. This finding may be further evaluated with bilateral decubitus radiographs to assess for air trapping with the side of foreign body aspiration failing to deflate in the dependent position (Figure 3b and c). Lateral decubitus radiography, however, have only 68–74% sensitivity and 45–67% specificity ¹¹. Furthermore, it has been shown to increase false-positive rates without increasing the rate of true-positive identification. As such, a negative chest radiography in the setting of high clinical suspicion should prompt further evaluation with CT.

CT scan has an accuracy close to 100% for the detection of aspirated foreign body ¹¹ able to identify both an endoluminal mass as well as secondary signs of aspiration. Because of the increased radiation exposure of CT as compared with radiography, study benefits must be weighed. 3D virtual bronchoscopy reconstructions can be utilized to assess foreign body aspiration and may be used for preprocedural planning. Additionally, following bronchoscopic removal, CT can be used to assess for residual aspirated foreign body ¹².

The definitive diagnosis and management of a foreign body typically involves bronchoscopy to remove the offending object. However, no universal standard of care has been thoroughly defined. Rigid bronchoscopy has been described to have several key benefits compared to flexible bronchoscopy for definitive management. Some cited reasons include: 1) the ability to ventilate via the rigid bronchoscope, 2) improved visualization with a rigid telescope, and 3) greater versatility to accommodate various sizes of suctioning and optical forceps. Additionally, the rigid scope offers a wider space to manipulate the offending object and to facilitate removal while avoiding obstruction at the level of the glottis. In cases of diagnostic uncertainty or complexity such as in recurrent pneumonia with no clear history of an aspiration, a flexible bronchoscopy may be the preferred initial test.

According to one study, when a combination of three or more highly suggestive clinical and radiological diagnostic data were noted, the risk of identifying a foreign body in the airway was 91%. Diagnostic clinical criteria significantly correlated with the presence of a foreign body included: a history of sudden choking, cyanosis, apnea, and decreased breath sounds. Diagnostic radiological criteria included: atelectasis, mediastinal shift, or signs of air trapping. The absence of the aforementioned criteria was very predictive of a negative flexible bronchoscopy. Thus, it was deemed safe to refer these patients for outpatient follow-up as opposed to initial bronchoscopy ¹³.

Lungs anatomy and function of the airway

An infant is developmentally able to suck and swallow and is equipped with involuntary reflexes (gag, cough, and glottic closure) that help to protect against aspiration during swallowing. Dentition initially develops at approximately 6 months with eruption of the incisors. Molars are required for chewing and grinding food and do not erupt until approximately 1.5 years of age. However, mature mastication abilities take longer to develop and remain relatively incomplete throughout early childhood ¹⁴. Young children and children with developmental and neurologic impairment also do not have the overall cognitive skills, behavioral control, or experience to chew well and eat slowly.

Despite a strong gag reflex, a young child’s airway is more vulnerable to obstruction than that of an adult in several ways. The smaller diameter is more likely to experience significant blockage by small foreign bodies. Resistance to air flow is inversely related to the radius of the airway to the fourth power, so even small changes in the cross-section of the airway of a young child can lead to dramatic changes in airway resistance and air flow. Mucus and secretions around a foreign body in the airway will reduce the radius of the airway even further and may also form a seal around the foreign body, making it more difficult to dislodge by forced air, such as with a cough or Heimlich maneuver. The force of air generated by a cough in an infant or young child is less than that in an adult; therefore, a cough may be less effective in dislodging a complete or partial airway obstruction during early childhood ¹⁵.

Airway anatomy in children differs from anatomy in adults. The narrowest portion of the pediatric airway is the cricoid, while in adults the narrowest portion is the glottis. Thus particles may be large enough to be aspirated past the vocal cords (glottis) in children only to become lodged in the subglottis at the area of the cricoid, to potentially devastating effect. When considering aspiration of foreign objects, children have a slight predominance for aspiration into the right mainstem bronchus, but this proclivity increases with age owing to a more vertical orientation of the right mainstem in adults that parallels the orientation of the trachea – it becomes the most dependent and direct portion of the adult airway.

Figure 1. Lung anatomy

Figure 2. Bronchial tree of the lungs

Figure 3. Foreign body aspiration

Footnote: A 30-month-old boy with an endobronchial non-radiopaque foreign body aspiration who presented with acute onset of wheezing and respiratory distress. (a) Frontal chest radiograph shows asymmetric hyperinflation of the right lung (asterisk) as compared with the normally aerated left lung. (b) Left lateral decubitus radiograph demonstrates expected deflation of the left lung (asterisk) in the dependent portion. (c) Right lateral decubitus radiograph shows persistent relative hyperinflation representing air trapping of the right lung (asterisk) despite dependent positioning. Radiographic findings suspicious for aspirated non-radiopaque foreign body in the right main stem bronchus. Subsequently obtained bronchoscopy demonstrated a nearly obstructive foreign body (likely almond) located within the right main stem bronchus

[Source ¹⁶ ]

Foreign body aspiration causes

Any object that can be placed into the mouth can potentially be aspirated. This is of particular concern in infants and young children who explore and interact with their environment by placing objects into their mouth; parental vigilance regarding which objects are available to an unsupervised child is paramount. Similarly, infants’ and young children’s swallowing coordination has not fully developed, and there is a proclivity to inhale or aspirate foods when eating. The lack of molars to chew food is also a contributing factor in children ¹⁷. Peanuts being the most commonly aspirated food, followed by hotdogs and hard candy, with hotdogs causing the most mortality. Male children are more likely to aspirate than female children ¹⁷. Food or other objects with a smooth, round shape are the highest risk for aspiration (nuts, beans, grapes, hotdogs/sausages, etc), and a primary prevention strategy is to prepare such foods in a way so as to change this shape to something more angular and easier to chew and swallow (by quartering grapes, for example).

Foreign body aspiration pathophysiology

Young children are particularly at risk for foreign body aspiration. One study has shown the mean age to be 24 months with 98% of cases involving children < 5 of age. As airway resistance is inversely related to the cross sectional radius by a power of four, the relatively smaller diameter of pediatric airways means that they are more prone to significant airflow obstruction with even small foreign bodies. Dental development also contributes to the risk of foreign body aspiration, as molars typically are not present before the age of 2; thus children in this age group are able to bite pieces of food with their incisors but not effectively able to grind food into smaller pieces. Additionally, young children tend to explore the world with their mouths while playing and exhibit high levels of activity and distractibility while eating, further putting them at risk. Due to the relative anatomical narrowing of the tracheobronchial tree in children, the proximal airway is typically the site of obstruction. In fact, in one retrospective review, 96% of foreign bodies aspirated were found in this location. In children <15 years of age, foreign bodies lodge within the left lung almost as often as in the right lung. This is due to the symmetric tracheal take-off angle found between the two bronchi in many children prior to the development of a prominent aortic indent affecting the trachea and left main bronchus. Regardless of age, if there is noticeable aortic indentation on the trachea when examining radiographs, then the right bronchial angle will be less distinct compared to the left side and aspiration will be more common in the right lung ¹⁸.

Foreign body aspiration symptoms

Patients may be completely asymptomatic and the only evidence of an aspiration event may be found during history taking. Upon aspiration of a foreign body into the larynx or proximal trachea, there is always the potential for respiratory compromise or for further inhalation into the distal airways causing subacute symptoms including shortness of breath, wheezing, or coughing. However, sudden onset of cough, choking, and/or shortness of breath (dyspnea) have been found to be the most common symptoms. One prospective study has cited a sensitivity of 91.1% and specificity of 45.2% for choking and acute cough. Wheeze on auscultation has been found to be a major physical finding and in one study was documented in 60% of cases. In the same study, 32% of patients had asymmetric breath sounds. An abnormal physical exam has been seen to have a sensitivity of 80.4% and specificity of 59.5% for foreign body aspiration ¹⁹.

Chronic shortness of breath can be related to aspiration of a foreign body, especially in children and developmentally delayed individuals who are unable to articulate the event reliably. This is more likely to be in the smaller, more distal airways and symptoms can relate either to complete occlusion of a terminal bronchus and development of pneumonia or to partial obstruction leading to wheezing, coughing, stridor, and progressive symptoms as the surrounding respiratory epithelium becomes more reactive and edematous. The patient may have several weeks of coughing, shortness of breath, or even complain of chest discomfort. Such patients may present weeks to months later, and the initial aspiration event may have been unknown or forgotten by patients and families.

Foreign body aspiration complications

A myriad of complications including recurrent pneumonia, bronchiectasis, lung abscess, and atelectasis can occur from a missed foreign body aspiration. Bronchial stenosis is also a well-known complication of chronic foreign bodies in the airway. However, nearly universal, tracheal lacerations are the most commonly reported complication among affluent countries. Pneumonia is the most common complication among countries with a poorer socioeconomic status. In a retrospective study evaluating risk factors associated with a missed diagnosis of foreign body aspiration, the incidence of a major complication was often seen to be increased the longer a foreign body was present in the airways. Obstructive emphysema was found to be the most common complication for foreign bodies discovered >3 days after the initial event. Importantly, it should be noted that a normal radiograph with absent physical findings does not exclude the possibility of an aspirated foreign body. Furthermore, patients on bronchodilators and steroid may suppress reactive respiratory symptoms ¹⁹.

Foreign body aspiration diagnosis

The diagnosis of an aspirated foreign body is based on a combination of the history of the child’s illness, the child’s presenting symptoms, and chest X-rays. If a foreign body in the airway is strongly suspected, a child needs to go to the operating room and have an airway examination performed under anesthesia. This examination is called a microlaryngoscopy and bronchoscopy (a look at the voice box and windpipe, or airway).

A child may be diagnosed with foreign body in the airway when a family member has seen the child swallow food or a small object then noticed signs of airway distress, like coughing or difficulty breathing. Children with a persistent segmental pneumonia, especially right lower lobe, should also be considered for foreign body aspiration.

There are three primary ways to see if a child has inhaled something into the airway or lungs:

• Chest X-ray. Some non-food items can be seen in the airway or lungs using a traditional X-ray. However, most food, vegetable matter and plastic toys won’t appear on chest X-ray films.
• Inspiratory and expiratory phase X-ray. These are X-rays taken when the child has inhaled and then exhaled the air out of their lungs. If a foreign body cannot be seen with a traditional X-ray, then inspiratory and expiratory phase films may show hyperinflation or air-trapping which suggests an aspirated foreign body.
• Bronchoscopy. When suspicion of aspiration is high enough but the physical exam and X-rays are not definitive for a diagnosis, an instrument called a bronchoscope is inserted through the mouth and used to look at the inside of the airways under anesthesia. Bronchoscopy can be used both to locate the foreign body and to remove it.

Chest radiographs are often utilized as initial tool of investigation for foreign body aspiration. Radiological findings consistent with a foreign body aspiration include atelectasis, pneumothorax, and air trapping. However, chest radiographs have been seen in multiple studies to be frequently normal, with one study citing a normal chest radiograph in 35% of cases of foreign body aspiration. This same study indicated that the most common abnormality found on radiograph was air trapping, present in 53% of cases. The sensitivity of chest radiograph has been documented as 67.9% and the specificity has been seen to be 71.4%. In one study, children with a concerning history of sudden cough, abnormal pulmonary exam, and abnormal chest x-ray have been shown to have a risk of 88.6% for foreign body aspiration. It is important to note that rarely a single finding or historical piece of information can definitively diagnose a foreign body aspiration. Rather, direct identification via bronchoscope is often needed.

In a review of common imaging modalities for diagnosis of foreign body aspiration, a simple algorithm based on feasibility and utility was generated at one institution. Recommendations included initial diagnostic work-up with frontal and lateral chest films with additional neck films if warranted on exam. Abnormalities at this stage would be sufficient to necessitate bronchoscopy. However, if the radiographs are unrevealing in the symptomatic patient with a suggestive history, a CT of the chest should subsequently be performed. If CT is unavailable and the child is > 5 years of age, then inspiratory-expiratory films can be obtained. If the child is younger than 5 years old, bilateral decubitus films are preferred. Fluoroscopy and MRI can be used as adjunctive measures. It should be noted that this was an algorithm formulated at one particular institution and is not universal practice.

To mitigate the potential need for CT scan, one study has evaluated a quantitative method to increase the sensitivity of radiographs to detect foreign bodies, in particular aspirated objects which are radiolucent. In a case-control study, radiodensity ratios were compared between the affected lung and the contralateral lung in patients with definitively diagnosed foreign body aspiration and healthy controls. The radiodensity ratio was seen to be significantly higher in in patients with aspiration as compared to controls. Radiodensity was calculated for each lung by measuring total Hounsfield units and then the ratio developed involved comparison between the affected lung and the normal lung. The authors of this study suggest a radiodensity ratio cutoff of 1.10 is sufficiently positive to warrant further investigation with bronchoscopy, whereas a ratio below this value would warrant further work-up with a CT scan. As there is a relative paucity evaluating this method in the literature, further studies are needed for validation ²⁰.

Foreign body aspiration treatment

Bronchoscopy is the standard method for removal of an aspirated foreign body. An anesthesiologist puts the child into a deep sleep and then topical lidocaine spray is used to further anesthetize the child’s larynx. An instrument called a laryngoscope is inserted into the airway to view the larynx; then a rigid, ventilating bronchoscope is passed beyond it, into the airway, and used to examine the trachea and right and left bronchi to locate the foreign body.

When the object is found, specially designed forceps are inserted into the airway through the bronchoscope to retrieve the object. This procedure requires training, delicacy and skill.

There are three kinds of forceps that may be used to remove airway foreign bodies:

• Optical forceps with an attached telescope to view the retrieval of the object
• Non-optical forceps used to remove beads, nails, screws, tacks and other objects that are in a distant tiny space
• Biopsy forceps used to remove new or granulating tissue or tissue masses, which can form as the body attempts to enclose a foreign body that has been present for an extended period

Very rarely, the doctor may make a tracheotomy incision (an incision that opens the child’s airway) to extract a foreign body that is difficult to remove due to its size or shape.

The child will typically stay in the hospital overnight after the procedure for observation. There may be airway swelling, increased secretions, infection or difficulty breathing after the foreign body is removed. Occasionally, if a foreign body has been left in a child for a long period of time, the child may require additional bronchoscopies to make sure that all of the foreign body has been removed and that there is no residual scarring or granulation tissue. Sometimes the child requires antibiotics, steroids or inhaled bronchodilators for a brief period of time after a foreign body is removed from the airway.

Foreign body aspiration prognosis

A large retrospective review identified the mortality rate among pediatric patients with foreign body aspiration to be 2.5%. Age was seen to be correlated with the anatomic location of the foreign body with increasing age positively correlated to increasing distal anatomic location of the aspiration. Unsurprisingly, neurologic disability was the most common condition among patients with aspiration. This particular co-morbidity was associated with increased odds of death and mechanical ventilation. A lodged foreign body lower in the respiratory tract carried a comparatively higher odds of mortality compared to those proximally positioned. It is believed by the authors that this is secondary to significant mucous plugging along with later dislodgement resulting in contralateral obstruction and hypoxia. Despite this, foreign bodies present in the trachea had the highest odds of requiring mechanical ventilation ²¹.

References

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Bronchopulmonary sequestration

Bronchopulmonary sequestration also called accessory lung or pulmonary sequestration, is a rare congenital cystic piece of abnormal lung tissue that doesn’t function like normal lung tissue. It can form outside (extralobar) or inside (intralobar) the lungs, but is not connected directly to the airways. Bronchopulmonary sequestration consists of a nonfunctioning mass of lung tissue that lacks normal communication with the tracheobronchial tree and receives its arterial blood supply from the systemic circulation ¹. The blood supply to bronchopulmonary sequestration is through aberrant vessels from systemic circulation, most commonly the descending thoracic aorta ². The abnormal tissue can be microcystic, containing many small cysts, or macrocystic, containing several large cysts. The term sequestration is derived from the Latin verb sequestare, which means ‘to separate’ and it was first introduced as a medical term by Pryce in 1964 ³. Bronchopulmonary sequestration is rare, representing about 1 to 6% of all congenital lung anomalies and may go undetected during the prenatal period and early childhood years ⁴. Some authors propose a greater male prevalence (this may be the case for the extralobar type) ⁵. The age of presentation is dependent on the type of bronchopulmonary sequestration. Nearly one-half of the adult patients diagnosed with bronchopulmonary sequestration manifested no relevant symptoms.

Bronchopulmonary sequestration is divided into two types:

1. Intralobar bronchopulmonary sequestration in which the mass forms inside the lungs. These lesions account for about 75% of cases of bronchopulmonary sequestration, affect males and females equally, and are generally isolated birth defects. All intralobar lesions require surgical removal (resection) after birth.
2. Extralobar bronchopulmonary sequestration in which the abnormal mass forms outside but nearby the lungs. In some instances, extralobar bronchopulmonary sequestration may be located in the abdomen. These lesions account for only about 25% of bronchopulmonary sequestration cases, and are more likely to affect males than females. Small extralobar bronchopulmonary sequestration can frequently be managed without surgery after birth, while large lesions will require surgery.
   
   • Extralobar intrathoracic
   • Extralobar subdiaphragmatic

Intralobar bronchopulmonary sequestration which is the more common type, where the lesion lies within pleural layer surrounding the lobar lung and extralobar bronchopulmonary sequestration which has its own pleural covering, maintaining complete anatomic separation from adjacent normal lung ⁶.

Most patients with intralobar bronchopulmonary sequestration present in adolescence or early adulthood with recurrent pneumonias in the affected lobe ⁴. Patients with bronchopulmonary sequestration can be asymptomatic and the diagnosis achieved incidentally. Other presenting symptoms may include cough, hemoptysis, chest pain and dyspnea ⁷. Extralobar bronchopulmonary sequestration is often identified on prenatal ultrasound and becomes symptomatic early in life, whereas intralobar bronchopulmonary sequestration is more commonly identified later in life secondary to recurrent infection. Extralobar bronchopulmonary sequestration rarely becomes infected because it is separated from the tracheobronchial tree by its own pleural investment ⁴.

Bronchopulmonary sequestration is one of several types of congenital lung lesions and may be confused with congenital cystic adenomatoid malformation (CCAM). While similar in some ways, bronchopulmonary sequestration and CCAM are unique conditions that require individualized treatment. A child can also develop a hybrid lesion, which has characteristics of both a bronchopulmonary sequestration and CCAM. This unusual condition makes diagnosis challenging.

Treatment for bronchopulmonary sequestration depends on the type and size of lung lesion, as well as whether the condition is causing any serious health complications for mother or baby.

While some cases of small extralobar bronchopulmonary sequestrations will not require surgery, large extralobar bronchopulmonary sequestrations and all intralobar bronchopulmonary sequestrations can lead to breathing problems, infection, and life-threatening complications like heart failure. Surgery is needed to remove the abnormal tissue.

Most children with bronchopulmonary sequestration can be safely treated with surgery after birth. In rare cases — when the lesion has grown abnormally large, is restricting lung growth or impairing blood flow, putting your baby at risk for heart failure — fetal intervention may be necessary.

It has been generally believed that most patients should have their bronchopulmonary sequestration resected even if they are asymptomatic due to concerns regarding eventual complication, mainly infection of bronchopulmonary sequestration. However, this issue remains debatable since data regarding the long-term clinical course and outcome of those with unresected bronchopulmonary sequestration are sparse, particularly in the adult population ². A cohort study included adults in their third to seventh decades of life without symptoms referable to the presence of bronchopulmonary sequestration and no relevant symptoms or events occurred during follow-up of patients with unresected bronchopulmonary sequestration ².

Petersen et al. ⁸ reviewed the literature for patients above the age of 40 with intralobar bronchopulmonary sequestration and found 15 cases including two patients from their own medical center. Most of these adult patients underwent surgical resection of their intralobar bronchopulmonary sequestration. The largest study in the literature on bronchopulmonary sequestration is from China where Wei et al. ⁷ reported 2625 cases of bronchopulmonary sequestration including 132 adult patients. However, their report does not describe how many of their adult bronchopulmonary sequestration patients underwent surgical resection, associated surgical outcome, nor clinical course of patients who did not undergo surgical resection ⁷. In a study by Makhija et al. ⁶, 102 older patients (age 4 to 80 years) with congenital cystic lung disease undergoing surgical management were reported and included 20 with bronchopulmonary sequestration (20%); postsurgical complication rate of 9.8% for the entire cohort was reported.

Berna et al. ⁹ studied 26 adult patients with intralobar bronchopulmonary sequestration all of whom underwent surgical resection. Hemoptysis or recurrent infection was present in 54%. All 26 patients underwent surgical resection of their bronchopulmonary sequestration including 20 patients (77%) who underwent lobectomies. Postoperative complication rate was 25% and included pleural empyema, hemoptysis, prolonged air leak, arrhythmia, and fistulae. All patients were alive and well at long-term follow-up (mean 36.5 months).

The surgical resection of sequestration carries the risk of complications; the surgical complication rate in a cohort was 28% which included chylous leak, intraoperative mild bleeding, chronic chest pain, arm numbness and pneumonia. No surgical mortality occurred. These results are similar to those reported by Berna et al ⁹.

Figure 1. Congenital pulmonary sequestration

Intralobar bronchopulmonary sequestration

Intralobar bronchopulmonary sequestration is a subtype of pulmonary sequestration. Intralobar bronchopulmonary sequestration is the commoner type of pulmonary sequestration (four times commoner than extralobar bronchopulmonary sequestration), accounting for 75% of all sequestrations and is characterized by the sequestration surrounded by normal lung tissue without its own pleural covering. Patients usually present before the third decade with recurrent infection. There is strong predilection for intralobar bronchopulmonary sequestration towards the lower lobes (predominantly left lower lobe).

There is increasing data to support the concept of sequestrations stemming from recurrent infections that produce aberrant arterial vessels arising from the aorta ¹⁰. Feeding vessels include branches from the thoracic aorta (75%), abdominal aorta, intercostal artery or multiple arteries.

Extralobar bronchopulmonary sequestration

Extralobar bronchopulmonary sequestration is a subtype of bronchopulmonary sequestration. Extralobar pulmonary sequestration is usually encountered in infants, most being diagnosed before six months. Extralobar pulmonary sequestration is the less common type of pulmonary sequestration, accounting only for 15-25%. It is more common in male (M:F 4:1).

Extralobar bronchopulmonary sequestration is covered by its own pleura and this is what differentiates extralobar bronchopulmonary sequestration from intralobar bronchopulmonary sequestration. There is strong predilection for extralobar bronchopulmonary sequestration towards the left lower lobe (65-90%). Of these, 75% are found in the costophrenic sulcus on the left side. They may also be found in the mediastinum, pericardium, and within or below the diaphragm.

Extralobar bronchopulmonary sequestration receives vascular supply mainly from the aorta (thoracic or abdominal) or from other arterial vessels (splenic, subclavian, gastric, intercostal or multiple vessels) and venous drainage can be either systemic or pulmonary.

Extralobar bronchopulmonary sequestrations are associated with other congenital malformations in more than 50% of cases, such as congenital diaphragmatic hernias, congenital pulmonary airway malformation (CPAM) type II (hybrid lesions), and congenital heart disease ¹¹.

Bronchopulmonary sequestration causes

Scientists do not know what causes bronchopulmonary sequestration. Bronchopulmonary sequestration is believed to result from abnormal diverticulation of foregut and aberrant lung buds  ¹². Most clinicians believe the condition begins during prenatal development when an extra lung bud forms and migrates with the esophagus. Depending on when the extra lung bud forms, it may become part of one of the lungs (intralobar), or grow separately (extralobar).

Bronchopulmonary sequestration has not been linked to a genetic or chromosomal anomaly, and does not appear to run in families (is not hereditary).

The most frequently supported theory of pulmonary sequestration formation involves an accessory lung bud that develops from the ventral aspect of the primitive foregut. The pluripotential tissue from this additional lung bud migrates in a caudal direction with the normally developing lung. It receives its blood supply from vessels that connect to the aorta and cover the primitive foregut. These attachments to the aorta remain to form the systemic arterial supply of the sequestration ¹³

Early embryologic development of the accessory lung bud results in formation of the sequestration within normal lung tissue. The sequestration is encased within the same pleural covering. This is the intrapulmonary variant. In contrast, later development of the accessory lung bud results in the extrapulmonary type that may give rise to communication with the gastrointestinal tract. Both types of sequestration usually have arterial supply from the thoracic or abdominal aorta. Rarely, the celiac axis, internal mammary, subclavian, or renal artery may be involved ¹⁴.

Intrapulmonary sequestration occurs within the visceral pleura of normal lung tissue. Usually, no communication with the tracheobronchial tree occurs. The most common location is in the posterior basal segment, and nearly two thirds of pulmonary sequestrations appear in the left lung. Venous drainage is usually via the pulmonary veins ¹⁵. Foregut communication is very rare, and associated anomalies are uncommon.

Extrapulmonary sequestration is completely enclosed in its own pleural sac. It may occur above, within, or below the diaphragm, and nearly all appear on the left side. No communication with the tracheobronchial tree occurs. Venous drainage is usually via the systemic venous system. Foregut communication and associated anomalies, such as diaphragmatic hernia, are more common.

Bronchopulmonary sequestration symptoms

Symptoms of bronchopulmonary sequestration can vary, and depend on the size of the lesion.

After birth, children with bronchopulmonary sequestration may experience:

• No symptoms
• Trouble breathing
• Wheezing or shortness of breath
• Frequent lung infections like pneumonia
• Upper respiratory infections that take longer than usual to resolve
• Feeding difficulties and trouble gaining weight as infants

All suspected lung lesions, whether found before or after birth, require careful imaging. Determining the type, size and location of the lesion will guide treatment recommendations.

Intrapulmonary sequestration

Although an intrapulmonary sequestration is usually diagnosed later in childhood or adolescence, symptoms may begin early in childhood with multiple episodes of pneumonia. A chronic or recurrent cough is common. Intrapulmonary sequestration shares the visceral pleura that covers the adjacent lung tissue and is usually located in the posterobasal segment of the lower lobes. The thoracic or abdominal aorta often provides the arterial blood supply. Venous drainage is commonly provided to the left atrium via the pulmonary veins.

An elemental communication with other bronchi or lung parenchyma may be present, allowing infection to occur. Rarely, an esophageal bronchus may be present. Resolution of infection is usually slow and incomplete because of inadequate bronchial drainage.

Overdistension of the cystic mass with air can result in compression of normal lung tissue with impairment of cardiorespiratory function. Aeration probably occurs through the pores of Kohn.

Other congenital anomalies may appear in 10% of cases.

Extrapulmonary sequestration

Many patients present in infancy with respiratory distress and chronic cough. Lesions are commonly diagnosed coincidentally during investigation of, or surgery for, an associated congenital anomaly. Therefore, clinical symptoms may be absent or minor.

Extrapulmonary sequestration may manifest as gastrointestinal symptoms if communication with the gastrointestinal tract is present. As a result, infants may have feeding difficulties. In addition, extrapulmonary sequestration may manifest as recurrent lung infection, similar to the intrapulmonary form. This type of sequestration does not contain air unless communication with the foregut is present.

Bronchopulmonary sequestration diagnosis

Thanks to improvements in prenatal imaging, most cases of bronchopulmonary sequestration are discovered during routine ultrasounds between 18 to 20 weeks’ gestation. Pulmonary sequestrations are diagnosed with a prenatal ultrasound showing a mass in the chest of the fetus. A solid mass will typically appear on the ultrasound as a bright spot in the fetus’s chest cavity. The mass may displace the heart from its normal position or push the diaphragm downward, but the key feature of a sequestration is the artery leading from the cystic mass directly to the aorta. This is what distinguishes a pulmonary sequestration from a congenital cystic adenomatoid malformation (CCAM). Expert fetal imaging specialists experienced in evaluating fetal lung lesions can detect the source of the blood flow to the lung lesion as well how blood is drained from the lesion. This is an important step to confirm an accurate diagnosis and distinguish between an intralobar and extralobar bronchopulmonary sequestration, hybrid lesion, CCAM or other type of fetal lung lesions.

If you are carrying a baby suspected to have bronchopulmonary sequestration, you should be seen by a center with expertise in lung lesions for a more thorough examination.

Bronchopulmonary sequestration treatment

Nearly one-half of adult patients with pulmonary sequestration present with no relevant symptoms. The decision regarding surgical resection needs to weigh various factors including clinical manifestations related to bronchopulmonary sequestration, risk of surgical complications, comorbidities, and individual patient preferences.

Small or moderate-sized bronchopulmonary sequestrations that don’t change much during the pregnancy can be successfully managed after birth, usually with surgery to remove the abnormal lung tissue. These babies typically do not have any difficulty during pregnancy or after birth.

Management of an asymptomatic pulmonary sequestration with no connection to the surrounding lung is controversial; however, most experts advocate resection of bronchopulmonary sequestrations because of the likelihood of recurrent lung infection, high blood flow through the tissue can cause heart failure, the need for larger resection if the sequestration becomes chronically infected, and the possibility of hemorrhage from arteriovenous anastomoses ¹⁶. This surgery is quite safe even in the first year of life, and does not compromise lung function or development. These children will grow up normally and have normal lung function.

Surgical resection is the treatment of choice for patients who present with infection or symptoms resulting from compression of normal lung tissue.

Extrapulmonary lesions can usually be excised without loss of normal lung tissue.

Intrapulmonary lesions often require lobectomy because the margins of the sequestration may not be clearly defined. Complete thoracoscopic resection of pulmonary lobes in infants and children has been described with low mortality and morbidity ¹⁷.

Fetuses who do not have hydrops when bronchopulmonary sequestration is first detected must be followed closely with ultrasounds at least every week to look for the development of hydrops. Fetal hydrops is the build-up of excess fluid, which can be seen in the fetal abdomen, lungs, skin or scalp.

If the baby doesn’t develop hydrops, the medical team will continue to follow a “wait and see” approach with close follow-up. Many bronchopulmonary sequestrations begin to decrease in size before 26 weeks of pregnancy, and almost all can be safely dealt with after birth at a tertiary perinatal center. Some lesions even take care of themselves entirely.

A few fetuses develop fluid collection in the chest cavity, which may be treated by placing a catheter shunt to drain the chest fluid into the amniotic fluid.

If the fetus has a very large bronchopulmonary sequestration that will make resuscitation after delivery dangerous, a specialized delivery can be planned, called the ex utero intrapartum treatment (EXIT) procedure.

Management of pregnancy with bronchopulmonary sequestration

Depending on the gestational age of your baby and the size of the mass, you will continue to have regular ultrasounds to closely monitor the growth of the lung lesion.

Rarely, these masses can grow quite large, taking up valuable space in the chest. This can restrict normal lung growth and can lead to underdeveloped lungs which will not function adequately at birth. Large masses can also shift the heart and impair blood flow. This can lead to fetal heart failure (fetal hydrops) and cause the buildup of fluid in the fetus and placenta.

Some of these masses are associated with a large pleural effusion, or fluid collection in the chest cavity. This fluid collection can also compromise the ability of the fetal heart to function normally.

Over several visits, clinicians will determine how quickly your child’s bronchopulmonary sequestration is growing.

Fetal intervention for bronchopulmonary sequestration

Treatment for bronchopulmonary sequestration depends on the type and size of lung lesion, as well as whether the condition is causing any serious health complications.

Some babies with bronchopulmonary sequestration cannot wait for treatment after birth because the lesion is too large, growing too rapidly, or causing life-threatening complications in utero such as fetal heart failure.

Fetal interventions to treat bronchopulmonary sequestration include:

Draining fluid from the chest

A small number of bronchopulmonary sequestrations can develop a large pleural effusion, or accumulation of fluid in the chest, outside of the lung, which can compress the lungs and heart. This fluid can be drained prenatally and a shunt can be left in place to provide continued drainage of the fluid.

The shunting procedure itself is performed under ultrasound guidance. A large trocar (hollow needle) is guided through the mother’s abdomen and uterus, and into the fetal chest. The shunt is passed through the trocar to divert the accumulated fluid from the fetal chest to the amniotic sac. The shunt will remain until delivery. The goal of these procedures is to decrease the accumulation of fluid to ward off heart failure (fetal hydrops).

C-section to resection

Babies with large lung lesions can be safely delivered by C-section and be carried immediately to the adjacent operating room where expert fetal surgeons will remove the mass. After the mass is removed, a dedicated Neonatal Surgical Team will provide further specialized care for your baby.

Ex utero intrapartum treatment (EXIT) procedure

Rarely, a large bronchopulmonary sequestration may require a specialized delivery technique, such as the ex utero intrapartum treatment (EXIT) procedure. The EXIT procedure is performed in a Special Delivery Unit (SDU).

In an EXIT procedure, your surgical team will partially deliver the baby so that they are still attached to the placenta and receiving oxygen through the umbilical cord. This procedure allows time for fetal surgeons to establish an airway and remove the mass while the baby is still attached and supported by the mother. After removal, your baby will be delivered and our Neonatal Surgical Team will provide further specialized care.

Delivery of babies with bronchopulmonary sequestration

Mothers carrying babies with small lung lesions — without other associated anomalies — may be able to deliver at their local hospital, without the need for high-risk neonatal care. Babies with larger lesions, or those with complications or associated disorders, should be delivered in a center that offers expert care for both mother and baby in one location.

Babies with prenatally diagnosed lung lesions who will require treatment immediately or soon after birth are delivered in the Special Delivery Unit (SDU), specifically designed to keep mother and baby together and avoid transport of fragile infants.

Your baby will need immediate access to the Newborn/Infant Intensive Care Unit (NICU) and a dedicated Neonatal Surgical Team. Where a healthcare team experienced in performing complex, delicate procedures needed to establish an airway while delivering babies who may not be able to breathe on their own at birth, as well as any immediate surgeries that your baby might need is needed.

Surgery for bronchopulmonary sequestration after birth

Bronchopulmonary sequestration lesions can be successfully treated with surgery after birth.

• All intralobar bronchopulmonary sequestration lesions should be surgically removed because of an increased risk of infection as well as the potential for high blood flow through the tissue that can lead to heart failure later in life.
• Large extralobar bronchopulmonary sequestration, especially those with high blood flow, may compromise your baby’s ability to breathe or put too much stress on your baby’s heart, and should be surgically removed.
• Small extralobar bronchopulmonary sequestration may not require surgery to remove the lesion.

Removing the bronchopulmonary sequestration mass when your child is young has multiple benefits, including promoting compensatory lung growth (ability of lungs to grow and fill the space in the chest) and avoiding potential complications such as lung infections.

First, you will come in for an appointment for your child to be evaluated by the surgical team. A CT scan with contrast will be performed to confirm the diagnosis and determine the exact location of your child’s lung lesion.

The average length of stay after lung lesion surgery is two to three days.

Follow-up care

Follow-up care for children with bronchopulmonary sequestration will depend on the treatment the child received.

Most children treated for small lesions after birth will only need monitoring for the first year after surgery to ensure normal lung growth and lung function. The majority will require no additional long-term follow-up care.

Children treated for more severe or complex lung lesions may require ongoing monitoring through childhood. For those who experience limited lung growth resulting in pulmonary hypoplasia, comprehensive long-term care with a focus on improving your child’s pulmonary health, evaluating neurodevelopmental growth, meeting nutritional needs, monitoring for late onset hearing loss or any surgical issues, and more.

Bronchopulmonary sequestration prognosis

Most babies with bronchopulmonary sequestration have a very good outcome and have normal lung function after their lesions are removed. This is due to rapid compensatory lung growth that occurs during childhood. Having surgery early maximizes this compensatory growth.

The pulmonary sequestrations remain the same size or grow with the fetus, but usually do not cause severe problems, probably because there is enough room for the normal part of the lung to grow. The mass may shrink in size before birth. In all these cases, the outlook for a normal life is excellent. These fetuses should be followed closely, delivered near term, and the pulmonary sequestration should be removed surgically after birth. Often the removal is an elective procedure in early childhood.

A small number of fetuses with pulmonary sequestrations may develop large pleural effusions — excess fluid in the chest cavity — and even signs of heart failure. Unlike congenital cystic adenomatoid malformations, which cause trouble because of their size, bronchopulmonary sequestrations may cause trouble because of the high blood flow through the tumor. These are the only cases that require treatment before birth.

Children with moderate to large lesions can also do extremely well, but their outlook depends on expert treatment to avoid potential complications. These babies require highly specialized expert care from time of diagnosis to delivery and surgery to ensure the best possible long-term outcomes.

References

1. Liechty KW, Flake AW. Pulmonary vascular malformations. Semin Pediatr Surg. 2008;17(1):9–16.
2. Alsumrain, M., Ryu, J.H. Pulmonary sequestration in adults: a retrospective review of resected and unresected cases. BMC Pulm Med 18, 97 (2018). https://doi.org/10.1186/s12890-018-0663-z
3. Pryce DM. Lower accessory pulmonary artery with intralobar sequestration of lung; a report of seven cases. J Pathol Bacteriol. 1946;58(3):457–67.
4. Walker CM, Wu CC, Gilman MD, Godwin JD, 2nd, Shepard J-AO, Abbott GF: The imaging spectrum of bronchopulmonary sequestration. Curr Probl Diagn Radiol 2014, 43(3):100–114.
5. Berrocal T, Madrid C, Novo S, Gutiérrez J, Arjonilla A, Gómez-León N. Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology. Radiographics. 2004;24(1):e17. doi:10.1148/rg.e17
6. Makhija Z, Moir CR, Allen MS, Cassivi SD, Deschamps C, Nichols FC 3rd, Wigle DA, Shen KR. Surgical management of congenital cystic lung malformations in older patients. Ann Thorac Surg. 2011;91(5):1568–73. discussion 1573
7. Wei Y, Li F. Pulmonary sequestration: a retrospective analysis of 2625 cases in China. Eur J Cardiothorac Surg. 2011;40(1):e39–42.
8. Petersen G, Martin U, Singhal A, Criner GJ. Intralobar sequestration in the middle-aged and elderly adult: recognition and radiographic evaluation. Journal of Thoracic & Cardiovascular Surgery. 2003;126(6):2086–90.
9. Berna P, Cazes A, Bagan P, Riquet M. Intralobar sequestration in adult patients. Interactive Cardiovascular & Thoracic Surgery. 2011;12(6):970–2.
10. Lee EY, Boiselle PM, Cleveland RH. Multidetector CT evaluation of congenital lung anomalies. Radiology. 2008;247(3):632-648. doi:10.1148/radiol.2473062124
11. Hadley GP, Egner J. Gastric duplication with extralobar pulmonary sequestration: an uncommon cause of “colic”. Clin Pediatr (Phila). 2001 Jun. 40(6):364.
12. Telander RL, Lennox C, Sieber W. Sequestration of the lung in children. Mayo Clin Proc. 1976 Sep. 51(9):578-84.
13. Corbett HJ, Humphrey GM. Pulmonary sequestration. Paediatr Respir Rev. 2004 Mar. 5(1):59-68.
14. Abel RM, Bush A, Chitty LS, Harcourt J, Nicholson AG. Congenital lung disease. Kendig’s Disorders of the Respiratory Tract in Children. 8th ed. Philadelphia, Pa: WB Saunders; 2012. 317-357.
15. Alivizatos P, Cheatle T, de Leval M, Stark J. Pulmonary sequestration complicated by anomalies of pulmonary venous return. J Pediatr Surg. 1985 Feb. 20(1):76-9.
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17. Albanese CT, Rothenberg SS. Experience with 144 consecutive pediatric thoracoscopic lobectomies. J Laparoendosc Adv Surg Tech A. 2007 Jun. 17(3):339-41.

Pulmonary hypoplasia

Pulmonary hypoplasia also called lung hypoplasia refers to deficient or incomplete development of parts of the lung, which can be unilateral or bilateral ¹, ². Pulmonary hypoplasia is characterized by small, underdeveloped lungs that can affect not only breathing but also heart function, ability to feed, hearing and overall development ³. Some children with pulmonary hypoplasia develop a related condition known as pulmonary hypertension, which causes high blood pressure in the arteries of the lungs (the pulmonary arteries). Over time, this pressure causes the pulmonary arteries to narrow, making the right side of the heart work harder as it forces blood through the narrowed arteries ⁴.

The true prevalence of pulmonary hypoplasia is unknown. The reported incidence is between 9 to 11 per 10,000 live births which is an underestimation, as infants with lesser degrees of hypoplasia likely survive in the neonatal period ⁵. Incidence also varies by cause. In cases of premature rupture of membranes at 15-28 weeks gestation, the reported prevalence of pulmonary hypoplasia ranges from 9 to 28% ⁶. Most cases are secondary to congenital anomalies (such as congenital diaphragmatic hernia and cystic adenomatous malformations) or complications related to pregnancy that inhibit lung development ⁷, ⁴. These include, but are not limited to, renal and urinary tract anomalies, amniotic fluid aberrations, diaphragmatic hernia, hydrops fetalis, skeletal and neuromuscular disease and conditions like pleural effusions, chylothorax and intrathoracic masses that cause compression of the fetal thorax ⁸.

Pulmonary hypoplasia may be primary or secondary. Primary pulmonary hypoplasia is extremely rare and routinely lethal. The severity of the lesion in secondary pulmonary hypoplasia depends on the timing of the insult in relation to the stage of lung development. This typically occurs prior to or after the pseudoglandular stage at 6-16 weeks of gestation ¹. In pulmonary hypoplasia, the lung consists of incompletely developed lung parenchyma connected to underdeveloped bronchi. Besides disturbances of the bronchopulmonary vasculature, there is a high incidence, approximately 50-85%, of associated congenital anomalies such as cardiac, gastrointestinal, genitourinary, and skeletal malformations. The diagnosis can result in a spectrum of respiratory complications ranging from transient respiratory distress, chronic respiratory failure, bronchopulmonary dysplasia to neonatal death in very severe cases. Strict diagnostic criteria are not established for pulmonary hypoplasia; various parameters such as lung weight, lung weight to body weight ratio, total lung volume, mean radial alveolar count and lung DNA assessment have been used to classify pulmonary hypoplasia ⁹.

Your child should be followed by a pediatric pulmonologist after birth so that appropriate diagnostic tests can be performed and routinely followed. Your child’s care and pulmonary hypoplasia treatment plan is based on their specific needs, taking into account each unique diagnosis and treatment your child has received. If early surgery is not performed during infancy, close follow-up of your child is needed. As some cystic lung abnormalities can spontaneously resolve over months to years. Newborns who have been referred for a cystic lesion observed by fetal ultrasonography may have complete resolution on postnatal chest CT. Also, the occurrence of pneumonia or repeated respiratory infections may suggest surgical intervention is needed in a patient who has been conservatively managed.

Various aerosolized medications such as bronchodilators and corticosteroids should be considered if symptoms suggest reactive airway disease or obstructive airway disease.

Persistent pulmonary arterial hypertension can be treated with various pulmonary vasodilators such as inhaled nitric oxide and sildenafil, and endothelin receptor inhibitors such as bosentan.

Pulmonary hypoplasia causes

Pulmonary hypoplasia occurs secondary to a variety of conditions that limit lung development. There are several key factors required for the adequate development of the lung. These are:

• sufficient amniotic fluid volumes
• adequate volume of the thoracic cavity
• normal breathing movement
• normal fluid within the lung

A deficiency in any of these could lead to pulmonary hypoplasia.

For lung development to proceed normally, physical space in the fetal thorax (chest cavity) must be adequate, and amniotic fluid must be brought into the lung by fetal breathing movements, leading to distension of the developing lung. Several studies have demonstrated that gestation age at rupture of membranes (15-28 weeks gestation), latency period (duration between rupture of membranes and birth) and the amniotic fluid index (AFI of less than 1 cm or 5 cm) can influence the development of pulmonary hypoplasia ¹⁰.

Most cases of pulmonary hypoplasia are secondary to other congenital anomalies or pregnancy complications. Some cases however can occur as a primary event ¹¹.

With secondary causes, it can result from factors directly or indirectly compromising the thoracic space available for lung growth.

Intrathoracic causes include:

• Congenital diaphragmatic hernia: most common intrathoracic cause
• Congenital cystic adenomatoid malformation (CCAM) or congenital pulmonary airway malformation (CPAM)
• Extralobar sequestration / pulmonary sequestration
• Agenesis of the diaphragm
• Mediastinal mass(es)/tumor(s)
  • Mediastinal teratoma
  • Thoracic neuroblastomas
• Congenital heart diseases with poor pulmonary (arterial) blood flow
  • Tetralogy of Fallot
  • Hypoplastic right heart
  • Pulmonary artery hypoplasia or unilateral absence of the pulmonary artery
  • Scimitar syndrome causing a unilateral right-sided pulmonary hypoplasia
  • Trisomies 18 and 21
• Pleural effusions with fetal hydrops, hydrothorax

Extra-thoracic causes include:

• Oligohydramnios and its causes
  • Potter sequence: fetal renal anomalies
  • Fetal renal agenesis
  • Urinary tract obstruction
  • Bilateral renal dysplasia
  • Bilateral cystic kidneys
  • Prolonged rupture of membranes (PROM)
  • Preterm premature rupture of membranes (PPROM)
• Skeletal dysplasias, especially those causing a narrow fetal thorax
  • Jeune syndrome (asphyxiating thoracic dystrophy)
  • Thanatophoric dysplasia
  • Achondroplasia
  • Achondrogenesis
  • Osteogenesis imperfecta
  • Short rib polydactyly syndrome
  • Campomelic dysplasia
• Large intra-abdominal mass compressing the thorax
• Neuromuscular conditions interfering with fetal breathing movements
  
  • Central nervous system (CNS) lesions
  • Lesions of the spinal cord, brain stem, and phrenic nerve
  • Neuromuscular diseases (eg, myotonic dystrophy, spinal muscular atrophy)
  • Arthrogryposis multiplex congenital secondary to fetal akinesia
  • Maternal depressant drugs

Other associations include:

• Fryns syndrome
• Meckel Gruber syndrome
• Neu-Laxova syndrome
• Pena-Shokeir syndrome

Fetal lung fluid and oligohydramnios

Maintenance of fetal lung volume plays a major role in normal lung development. Normal transpulmonary pressure of about 2.5 mm Hg allows the fetal lung to actively secrete fluid into the lumen ¹². The effect of stretch of the lung parenchyma induces and promotes lung development. Studies in sheep have demonstrated that tracheal ligation and therefore increased lung distension, accelerates lung growth whereas chronic tracheal fluid drainage has the opposite effect ¹³. Cohen and colleagues ¹⁴ have found that in-utero overexpression of the cystic fibrosis transmembrane conductance regulator (CFTR) increased liquid secretion into the lung, accelerating lung growth in a rat model.

Oligohydramnios is considered to be an independent risk factor for the development of pulmonary hypoplasia. This is likely due to reduced distending forces on the lung. Studies have demonstrated that severe oligohydramnios decreased lung cell size, alters cell shape and may also negatively affect Type 1 cell differentiation which ultimately induces pulmonary hypoplasia.

It has been postulated that the Rho-ROCK pathway can affect the growth of the lung epithelium. Embryonic mouse models have demonstrated that ROCK protein inhibitor decreases the number of terminal lung buds. There are currently several groups studying the role of the Rho/ROCK pathway which has potential therapeutic implications in the reversal of lung hypoplasia ¹⁵.

Role of growth factors

Several growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), promote cell proliferation and differentiation. Transforming growth factor family proteins like TGFß1 can oppose these effects.

Embryologically, lungs arise from the foregut. Thyroid transcription factor 1 (TTF-1) is thought to be the earliest embryologic marker associated with cells committed to pulmonary development. FGF signaling is thought to be essential in the formation of TTF-1 expressing cells and this is thought to occur even before the pseudoglandular stage of lung development. Sonic hedgehog (SHH) signaling is further responsible for branching morphogenesis and mesenchymal proliferation. Disruption of any of these pathway may result in primary pulmonary hypoplasia ¹⁶.

FGF7 and FGF10 promote epithelial proliferation and formation of the bronchial tree. Overexpression of FGF10 can also stimulate the formation of cysts in the rat lung ¹⁷. EGF promotes lung branching and Type II alveolar cell proliferation. PDGF plays a crucial role in alveolarization. VEGF promotes angiogenesis and the differentiation of embryonic mesenchymal cells into endothelial cells. Bone morphogenetic protein was thought to oppose lung growth; however recent data suggests that in the presence of mesenchymal cells, BMP4 is a potent inducer of tracheal branching ¹⁸. Aberrant expression of these growth factor proteins in the amniotic fluid during pregnancy have been implicated in abnormal lung development. Interestingly, higher concentrations of VEGF are seen in the amniotic fluid in the second and third trimester and may be a molecular marker for hypoxia which requires further investigation ¹⁹.

Congenital diaphragmatic hernia

The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia remains unclear. Several mechanisms have been suggested. The nitrofen model of congenital diaphragmatic hernia is widely accepted. Nitrofen is a human carcinogen and the retinoid acid signaling pathway is essential for the normal development of the diaphragm. Perturbation of this pathway with compounds such as nitrofen, can induce congenital diaphragmatic hernia and pulmonary hypoplasia. Esumi and colleagues demonstrated that that administration of insulin-like growth factor 2 (IGF2) to nitrofen-induced hypoplastic lungs lead to alveolar maturation ²⁰. Furthermore, recent data suggests that prenatal treatment with retinoic acid results in increased levels of placental IGF2 and promotes both placental and fetal lung growth in nitrofen induced congenital diaphragmatic hernia ²¹.

Interestingly, erythropoietin (EPO) is a direct target of retinoic acid. A recent study has demonstrated decreased levels of erythropoietin mRNA in the liver and kidney of rats which may explain modifications in the pulmonary vasculature in congenital diaphragmatic hernia ²².

A recent study has also suggested a possible role of interleukin 6 (IL-6) in inducing catch-up growth particularly in nitrofen pre-treated explant fetal rat lungs ²³.

In cases of congenital diaphragmatic hernia (congenital diaphragmatic hernia) associated with pulmonary hypoplasia, hypertrophy of the contralateral lung has been demonstrated, with associated pulmonary artery hypertension. The hypoxemia in pulmonary hypoplasia stems from hypoventilation and right-to-left extrapulmonary shunting.

Pulmonary hypoplasia symptoms

There is wide variation in the clinical presentation of pulmonary hypoplasia, depending on the extent of hypoplasia and other associated anomalies ¹⁸.

The history may include poor fetal movement or amniotic fluid leakage and oligohydramnios. The neonate may be asymptomatic or may present with severe respiratory distress or apnea that requires extensive ventilatory support. In older children, dyspnea and cyanosis may be present upon exertion, or a history of repeated respiratory infections may be noted.

The external chest may appear normal or may be small and bell shaped, with or without scoliosis. A mediastinal shift is observed toward the involved side, and dullness upon percussion is heard over the displaced heart. In right-sided hypoplasia, the heart is displaced to the right, which may lead to a mistaken diagnosis of dextrocardia. Breath sounds may be decreased or absent on the side of hypoplasia, especially over the bases and axilla.

Some infants may present with otherwise asymptomatic tachypnea, and other may have severe respiratory distress at birth requiring ventilatory support. Pneumothorax, either spontaneous or associated with mechanical ventilation, may occur.

Infants with secondary pulmonary hypoplasia may have associated congenital anomalies or features suggestive of neuromuscular diseases. Such patients may have myopathic facies, with a V-shaped mouth, muscle weakness, and growth restriction. Multiple genetic syndromes associated with primary pulmonary hypoplasia are reported in the literature such as Scimitar Syndrome, Trisomy 21, and Pena-Shokeir Syndrome (fetal akinesia) ²⁴.

Compression deformities due to prolonged oligohydramnios, contractures, and arthrogryposis may be present. The Potter facies (hypertelorism, epicanthus, retrognathia, depressed nasal bridge, low set ears) suggest the possibility of lung hypoplasia caused by the associated renal defects.

Abdominal masses, such as cystic renal diseases and an enlarged bladder, must be sought. Associated anomalies of the cardiovascular, gastrointestinal (eg, tracheoesophageal fistula, imperforate anus, communicating bronchopulmonary foregut malformation), and genitourinary systems, as well as skeletal anomalies of the vertebrae, thoracic cage, and upper limbs, may be found upon examination ²⁵.

Pulmonary hypoplasia complications

Complications in pediatric pulmonary hypoplasia are as follows:

• Mortality due to acute respiratory failure in the neonatal period
• Chronic respiratory failure or insufficiency
• Pneumothorax, either spontaneous or as a result of ventilatory support
• Persistent pulmonary hypertension caused by a reduced pulmonary vascular bed and worsened by hypoxia or a coexisting left-to-right intracardiac shunt
• Chronic lung disease of infancy caused by prolonged ventilatory support
• Airway abnormalities, including tracheobronchial compression and tracheomalacia caused by the displaced aorta and enlarged left pulmonary artery
• Restrictive lung disease due to reduced total lung capacity
• Recurrent respiratory infections
• Recurrent wheezing episodes
• Reduced exercise tolerance
• Scoliosis in adolescent years due to abnormal thoracic cage development
• Nutritional, musculoskeletal, neurological, and gastrointestinal comorbidities
• Delayed growth and development

Pulmonary hypoplasia diagnosis

If the cause of the pulmonary hypoplasia is renal pathology, serum creatinine, blood urea, and electrolytes levels should be measured to assess renal function.

Radiographs

Chest radiographic findings vary. The ribs may appear crowded with a low thoracic-to-abdominal ratio, and the chest wall is classically bell-shaped; however, lung fields are clear unless there is also coexisting respiratory distress syndrome. Pneumothorax or other forms of air leak are frequently present. Films may also show features of the neonate’s underlying condition. In severe cases, there may be mediastinal shift with a homogenous density on the involved hypoplastic side and compensatory herniation of the contralateral lung across the mediastinum. Rib deformities may be observed. See the images below.

2D and 3D ultrasonography

Thoracic circumference (TC), thoracic circumference to abdominal circumference (TC:AC) ratio and lung area (LA) are frequently used measurements to assess prenatal risk for pulmonary hypoplasia ⁹. Thoracic circumference (TC) and lung area (LA) are gestational-age dependent whereas TC:AC ratio is not affected by gestational age. All of these measurements have a high specificity (between 40-100%) but none have a high enough sensitivity to be used reliably in clinical practice. However, in fetuses with congenital diaphragmatic hernia, the observed to expected lung-to-head ratio (LHR) measured by two-dimensional ultrasound remains the best predictor of pulmonary hypoplasia ²⁶.

Three-dimensional ultrasound techniques, which include pulmonary volume measurement, appears to have a high sensitivity 92% and specific 84% and appears to be a reliable technique to predict pulmonary hypoplasia ²⁷. Barros and Colleagues ²⁸ found that lung volumes measurements using 3D ultrasound has a high sensitivity (83.3%) and specificity (100%) for predicting lethal pulmonary hypoplasia in infant with skeletal anomalies.

Targeted fetal ultrasonography may demonstrate renal malformations, oligohydramnios, and decreased fetal movements in fetal neuromuscular diseases. While this is readily available at most centers, diagnosing disease requires expertise and can be limited by the presence of maternal obesity, low amniotic fluid index (AFI) and fetal malposition ²⁹.

Autopsy studies have shown that pulmonary hypoplasia is associated with a reduction in a number of pulmonary vessels and with increased arterial smooth muscle thickness, which may lead to increased pulmonary vascular resistance and decreased pulmonary arterial compliance. Pulmonary vasculature remodeling and pulmonary hypertension is particularly common in congenital diaphragmatic hernia and results in high mortality ³⁰. Given abnormalities in the vasculature, Doppler ultrasonography has been studied as way to predict pulmonary hypoplasia. Determination of pulmonary artery blood velocity waveforms is one tool used to diagnose pulmonary hypoplasia, however as a single test is unreliable. Pulsatile index of the ductus arteriosus for predicting pulmonary hypoplasia had a sensitivity of only 37% and specificity of 2% which is again, not clinically reliable ³¹.

Other imaging studies

Echocardiography may be used to identify associated cardiac anomalies. The frequency of cardiovascular malformations associated with isolated congenital diaphragmatic hernia is 11-15% ³². The most common anomalies include atrial and ventricular septal defects, conotruncal defects, and left ventricular outflow tract obstructive defects.

Angiography is indicated to confirm the diagnosis of any aberrant pulmonary vessels, to rule out scimitar syndrome, and to confirm reduced pulmonary vascular bed.

MRI or magnetic resonance angiography (MRA) may also be used to identify the smaller pulmonary arterial supply to the affected lung and the presence of other abnormal vascular anatomy.

Both MRI and ultrasonography appear to be useful in determining the degree of pulmonary hypoplasia ³³. Particularly in congenital diaphragmatic hernia, MRI based total fetal lung volume (FLV) and fetal body volume (FBV) measurements are useful in predicting post-natal survival. Recent studies are also demonstrating that MRI based FLV:FBV ratio measurements are not only able to predict neonatal mortality but also able to predict extracorporeal membrane oxygenation (ECMO) requirement with high accuracy ³⁴.

Lung scintigraphy has been used to evaluate the degree of pulmonary hypoplasia in infants with congenital diaphragmatic hernia. One study suggested that lung scintigraphy is useful to predict long-term pulmonary morbidity and poor nutritional status in survivors of congenital diaphragmatic hernia ³⁵.

Other tests

Obtaining an ECG and/or echocardiogram is important to distinguish between dextrocardia and dextroposition caused by pulmonary hypoplasia. In dextrocardia, ECG findings include an inverted P wave and T in lead 1, with negative QRS deflection and a reverse pattern between aVR and aVL. A mirror image progression is observed from V1 to a right-sided V6 lead. A tall R in lead V1 or an RS ratio equal to or greater than 1 also suggests dextrocardia.

The frequency of cardiovascular malformations associated with isolated congenital diaphragmatic hernia is 11-15% ³². The most anomalies include atrial and ventricular septal defects, conotruncal defects, and left ventricular outflow tract obstructive defects.

Bronchoscopy or bronchography is indicated because the reduced size of a bronchus and its branches confirms the diagnosis.

Pulmonary function testing is difficult to obtain in the young age, however it may a useful tool in monitoring the course of the disease to assess lung maturation and development. A recent study has demonstrated that lung function remains abnormal in the first three years of life in children with congenital diaphragmatic hernia. This study revealed normalization of total lung capacity, however with increasing residual volumes likely due to pulmonary overinflation. They hypothesized that the pulmonary hyperinflation was not due to normal alveolarization that occurs in the first three years of life, but is likely due to overdistended, simplified air spaces that was functionally different from those seen in normally grown lungs ³⁶. Another study reported normalization of all lung function parameters after surgery by age 24 months ³⁷. As expected, lung function significantly correlated with increase in age, height, and, especially, weight.

Histologic findings

On autopsy, in pulmonary hypoplasia, the overall lung size is reduced, cell numbers are decreased, branches of airways may be narrower and fewer, alveolar differentiation may be reduced, and a surfactant deficiency may be present.

Histopathologic descriptions of pulmonary hypoplasia may have limited value since some may appear similar to normal lung. However, in other cases there may be a reduction in a number of pulmonary vessels (and smaller pulmonary arterioles) and increased arterial smooth muscle thickness, indicating the presence of pulmonary hypertension.

The diagnosis of pulmonary hypoplasia is made if the lung weight–to–body weight ratio is less than 0.015 in infants born before 28 weeks of gestation and less than 0.012 in infants born after 28 weeks of gestation, in conjunction with a mean radial alveolar count (RAC) of less than 4%. The radial alveolar count (RAC) provides a simple objective measurement of the “relative paucity of alveoli” or “crowding of bronchial structures, which is unaffected by the state of expansion of the lungs.

In addition, in infants with severe risk factors (renal anomalies, diaphragmatic hernia), lung hypoplasia may be diagnosed by a lung volume–to–body weight ratio less than the 10th percentile when assessed on age-specific reference values ³⁸.

Pulmonary hypoplasia treatment

In fetuses with pulmonary hypoplasia, interventions can be done prenatally and treatment goals should be established for postnatal care. Prenatal interventions are performed with the goal of delaying preterm labor and allowing for lungs to mature.

Preterm rupture of membranes without signs of fetal distress or intrauterine infection is treated conservatively with or without tocolytics, antibiotics, and steroids in various combinations. Antenatal corticosteroids enhance fetal lung maturation in pregnancies less than 34 weeks of gestation. If gestational age is uncertain, lung maturity can be determined by aspiration of amniotic fluid from the vaginal vault. The lamellar body counts are a direct measurement of surfactant production by type II pneumocytes. If this initial screen shows neither clearly mature nor immature fetal lung, then the lecithin/sphingomyelin (L/S) ratio can be determined from amniotic fluid. The risk of respiratory distress is very low when the L/S ratio is greater than 2.0.

Amnioinfusions and amniopatch techniques have shown promising results in the treatments of preterm labor. Amnioinfusion consists of instilling isotonic fluid into the amniotic cavity. Amniopatch consists of intraamniotic injection of platelets and cryoprecipitate with the goal of sealing amniotic fluid leak. Small cases series have reported that both techniques reduce perinatal complications and prolong pregnancy particularly in severe oligohydramnios ³⁹.

After delivery, the infant needs respiratory support, which can range from supplying supplemental oxygen to mechanical ventilation, including high-frequency ventilation and extracorporeal membrane oxygenation (ECMO). Ventilatory strategies that have veered toward the use of gentle volume recruitment, permissive hypercapnia, especially in cases of congenital diaphragmatic hernia (congenital diaphragmatic hernia), have led to increased survival and improved outcomes ⁴⁰. Fetal MRI based lung volume assessment may be useful in predicting the severity of pulmonary hypoplasia and may also predict the need for ECMO. Weidner and colleagues demonstrated lower FLV:FBV ratios in infants who required ECMO ⁴¹. While the timing of congenital diaphragmatic hernia repair for infant on ECMO remains controversial, there are studies that show that surgical repair of congenital diaphragmatic hernia while on ECMO, can be done safely and is associated with good survival and there may be increased mortality associated with delayed repair ⁴². Pulmonary hypertension contributes to significant mortality in patient with congenital diaphragmatic hernia and this particular subset of patients may have additional benefit from early ECMO support.

There is conflicting data regarding the efficacy of inhaled nitric oxide (iNO) to manage pulmonary hypertension secondary to congenital diaphragmatic hernia. Randomized controlled trials of inhaled nitric oxide (iNO) treatment for infants with congenital diaphragmatic hernia have shown marginal, if any, efficacy. Poor left ventricular function and/or left ventricular hypoplasia may account for some of the poor response to iNO. Infants with severe respiratory failure secondary to pulmonary hypoplasia and documented persistent pulmonary hypertension of the newborn may benefit from iNO, but the data are limited ⁴³. Aggressive ventilation in these infants causes overexpansion of lungs with compresses intra-alveolar capillaries which further aggravates pulmonary hypertension. If this is the case, hemodynamics should be optimized prior to initiating nitric oxide. More recently there are smaller population studies that show that nitric oxide may be beneficial as adjunct therapy in combination with Sildenafil and dopamine infusions to improve survival, but larger studies are needed ⁴⁴.

Low lung compliance associated with congenital diaphragmatic hernia is thought to be secondary to surfactant deficiency, although there is very limited and conflicting data regarding this theory. One study shows that infants with congenital diaphragmatic hernia had lower rates of synthesis of surfactant protein B (SP-B) and less SP-B in tracheal aspirates compared with age-matched controls without lung disease ⁴⁵. While surfactant is not contraindicated, it does not seem to provide additional survival benefit in infants with congenital diaphragmatic hernia.

Of note, overexpansion of hypoplastic lungs compresses intra-alveolar capillaries and aggravates pulmonary hypertension. Partial liquid ventilation has also been used; however, data are lacking to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome ⁴⁶.

Dialysis for support of renal function is provided in some cases, but it should be started only after careful consideration. Patients with severe chronic renal impairment with pulmonary hypoplasia have a poor prognosis; the ultimate outcome is difficult to improve, even with optimal renal and respiratory support.

Some studies suggest that strict infection control may improve the outcome of neonates with congenital diaphragmatic hernia without the need for extracorporeal membrane oxygenation (ECMO) ⁴⁷.

Medical management of cystic adenomatoid malformations (CCAM) and prognosis is dependent on the size of the lesion. Microcysts 58</ref> Spontaneous improvement and possible resolution may occur over months to years in many of these lesions ⁴⁸. Their management must be individualized, with very large lesions resulting in lung hypoplasia or fetal hydrops required possible fetal surgery ⁴⁹. In most cases of fetal lung lesions, continued observation with possible postnatal therapy occurs if respiratory distress or failure to thrive develops ⁵⁰.

Multiple studies have proven the importance of the retinoic acid signaling pathway in lung development as mentioned above. In keeping with this, the role of retinoic acid supplementation and antioxidants in pulmonary hypoplasia has been extensively studied. There is some promising human data that demonstrated decrease in incidence of bronchopulmonary dysplasia in extremely low birth infants who received vitamin A supplementation ⁵¹. There are also several animal models that show an increase in VEGF expression and increased lung alveolarization in response to vitamin A supplementation. Despite encouraging in vitro work, supplementation with vitamin A failed to reverse oligohydramnios-induced pulmonary hypoplasia in fetal rats.

Surgical treatment

A multidisciplinary team with expertise in fetal surgery should be involved, when feasible, in all cases of severe pulmonary hypoplasia. A major indication for fetal surgery is the presence of hydrops and a gestation of less than 32 weeks. In general cases that require surgical intervention are large cystic lung malformations and congenital diaphragmatic hernias.

Cystic lung malformations

Thoracocentesis or thoracoamniotic shunts can allow for drainage of fluid from the congenital cystic adenomatoid malformation (CCAM), but the fluid usually rapidly re-accumulates. Thoracoamniotic shunts may be offered in pregnancies complicated by hydrops secondary to the presence of a large or multiple communicating macrocysts or severe pleural effusions. Shunt placement has been reported to decrease congenital cystic adenomatoid malformation (CCAM) mass volumes by an average of 50%, and as much as 80% in some cases ³⁹.

In cases of significant mass effect due to congenital congenital cystic adenomatoid malformations (CCAMs) (or other solid lung mases) recommendations for delivery can range from an ex utero intrapartum treatment (EXIT) procedure with tumor resection while still on placental bypass, to elective cesarean delivery and immediate pediatric surgical evaluation and resection, to delivery with on-site pediatric surgical services. In cases in which masses plateau earlier in their growth phase, and presents a nonsignificant risk of pulmonary hypoplasia or hemodynamic compromise, surgery can be planned as an outpatient at age 4-6 week ⁵². Therefore, the management of the congenital cystic lung abnormalities needs to consider the spontaneous improvement and possible resolution that occurs over months to years in many of these lesions ⁴⁸. Up to 15% of prenatally diagnosed congenital cystic adenomatoid malformations (CCAMs) regress and may sonographically “disappear” by becoming isoechoic within the surrounding normal lung tissue. However, these lesions can still be identified on postnatal CT scan with contrast.

The risks of subsequent malignant degeneration of congenital cystic adenomatoid malformations (CCAMs) are poorly understood. After removal by lobectomy, the remaining normal ipsilateral lung demonstrates compensatory lung growth, and in general these children have no residual respiratory problems ⁵².

Thoracocentesis or thoracoamniotic shunts can allow for drainage of fluid from the congenital cystic adenomatoid malformation (CCAM), but the fluid usually rapidly reaccumulates. Thoracoamniotic shunts may be offered in pregnancies complicated by hydrops secondary to the presence of a large or multiple communicating macrocysts or severe pleural effusions. Shunt placement has been reported to decrease congenital cystic adenomatoid malformation (CCAM) mass volumes by an average of 50%, and as much as 80% in some cases ⁵².

Intrauterine vesicoamniotic shunts and endoscopic ablation of posterior urethral valves are other techniques that are currently used in fetuses with urinary tract obstruction and pulmonary hypoplasia. With careful case selection, pulmonary hypoplasia is prevented, and postnatal renal and respiratory function is improved ⁵³.

Congenital diaphragmatic hernia

In experimental animals, percutaneous fetal endoluminal tracheal occlusion (FETO) induces lung growth and morphologic maturation. Fetal endoluminal tracheal occlusion (FETO) with a clip may lead to accelerated lung growth and prevent pulmonary hypoplasia. Fetal endoluminal tracheal occlusion (FETO) is currently being studied at some centers across Europe, as a way to improve survival in cases of pulmonary hypoplasia associated with severe congenital diaphragmatic hernia ⁵⁴. There are variations in the technique but most centers prefer the non-invasive technique, where a balloon, inserted into the tracheal lumen at 22-28 weeks’ gestation ⁵⁵. Balloon occlusion creates a transpulmonic pressures, prevent fluid egress of fluid from the fetal lung which stimulate lung growth. It has been suggested that later insertion of the balloon beyond 29 weeks does not results in significant lung growth ⁵⁶. A recent study from Texas has reported improved postnatal outcomes in infants with severe congenital diaphragmatic hernia ⁵⁷. This procedure was found to be minimally invasive, may reverse pulmonary hypoplasia changes, and may improve survival rate in these highly selected cases. In addition, the airways can be restored before birth.

The optimal time of surgery for congenital diaphragmatic hernia repair varies from center to center. Surgical repair typically involves primary or patch closure of the diaphragm through an open abdominal approach. Successes have been reported with an endoscopic approach; however, it is associated with an increased incidence of hernia recurrence ⁵⁸. The decision is made based on the severity of the lesion, hemodynamics of the patient and the center’s preferences. Intraoperative considerations include the length of operative time, as thoracoscopic repair is associated with substantially longer operative times, leading to concerns for intraoperative instability, carbon dioxide retention, and pulmonary vasospasm for patients with moderate-to-severe pulmonary hypertension ⁵⁹. There are some studies that suggest that early intervention in patients on ECMO, reduced the total duration of ECMO, reduced surgical complications and increased survival. However, this data may be skewed toward patients who may have been too sick to be weaned off ECMO prior to surgery and further studies are needed ⁶⁰.

Follow up care

Since chronic lung disease is common in survivors of pulmonary hypoplasia, these infants and children have an increased risk of fatality and serious morbidity from upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs). Antiviral and antibiotics should be administered based on clinical symptoms and signs.

Children may be given bronchodilators and/or inhaled corticosteroids for the treatment of wheezing episodes and/or reactive airway disease.

Respiratory syncytial virus (RSV) prophylaxis should be considered during RSV season in infants younger than two years who have been treated with oxygen or medication for chronic lung disease within 6 months of the start of RSV season. Palivizumab is a humanized monoclonal antibody (IgG) directed against the fusion protein of RSV and has been shown to reduce the risk of hospitalization from RSV infection in high-risk pediatric patients by 55%. RSV season in most parts of the United States is from October to March. The dose is 15 mg/kg via intramuscular injection monthly throughout RSV season.

Children with pulmonary hypoplasia should receive the influenza vaccine at the start of every influenza season, which in the United States, while varying from season to season, begins as early as October. The influenza season peaks in January or February and continues as late as May.

Children with chronic lung disease are considered at high risk for invasive pneumococcal disease. If younger than two years, they should be administered the 13-valent pneumococcal conjugate vaccine (PCV13) 4-dose series at ages two, four, and six months, with a booster dose at 12-15 months. If aged 24 months to five years, they should receive 1 or 2 doses of PCV13 if they have not already completed the 4-dose series. Anyone over the age of two, with chronic lung disease, should also receive 1 dose of PCV23.

Pulmonary hypoplasia prognosis

Mortality has traditionally been very high. In a retrospective study of 76 premature infants less than 35 weeks’ gestation, 20 had prolonged rupture of membrane of more than 5 days and were clinically diagnosed with pulmonary hypoplasia. Of those 20 infants with pulmonary hypoplasia, 18 died. In another retrospective study of 117 infants of less than 37 weeks’ gestation who had prolonged rupture of membrane of more than 99 hours, 11 died and were considered to have pulmonary hypoplasia. The median age of death was 20 hours (range, 12-48 hours), mostly commonly from respiratory failure.

In different studies, mortality rates associated with pulmonary hypoplasia are reported to be as high as 71-95% in the perinatal period ⁹.

The following conditions increase the risk of mortality ⁶¹:

• Earlier gestational age at rupture of membranes, particularly at less than 25 weeks of gestation
• Severe oligohydramnios (amniotic fluid index < 4) for more than 2 weeks
• Earlier delivery (decreased latency period)
• Right-sided lesion
• Presence of genetic anomalies

To avoid mortality from severe lung hypoplasia in association with congenital diaphragmatic hernia or congenital cystic adenomatoid malformation (CCAM), fetal surgical intervention has been attempted. Most studies report a mortality rate of 25-30% in neonates with congenital diaphragmatic hernia andcongenital cystic adenomatoid malformation (CCAM) at high volume centers; mortality can be as high as 45% at peripheral care centers. However, in other cystic lung lesions, most are clinically asymptomatic and may not need aggressive management ⁶².

Risk factors for a poor outcome include the presence of hydrops fetalis, with a mortality rate as high as 80-90%. Other indicators include the type of congenital cystic adenomatoid malformation (CCAM) and its size. All of these factors reflect the degree of pulmonary compromise with lesions that result in varying degrees of pulmonary hypoplasia.

There is a recent retrospective study from Barcelona that studied 60 cases of pulmonary hypoplasia between 1995 to 2014, that found a mortality rate of 47% in the first 60 days of life and up to 75% in the first day of life ⁶³.

While antepartum amnioinfusions for treatment of oligohydramnios have significantly reduced the risk of pulmonary hypoplasia, longitudinal follow-up studies are lacking on the long-term outcomes of these children.

Of children with pulmonary hypoplasia secondary to congenital diaphragmatic hernia, the postnatal survival rate of congenital diaphragmatic hernia at tertiary centers has improved, with reported rates of 70-92% ⁶⁴. However, the survival rates do not account for the cases of congenital diaphragmatic hernia that are stillborn, died outside a tertiary center, or died as a result of spontaneous or therapeutic abortion.

Congenital diaphragmatic hernia survivors have a high incidence of respiratory, nutritional, musculoskeletal, neurological, and gastrointestinal morbidities ⁶⁴. In a prospective study of 41 congenital diaphragmatic hernia survivors, abnormal muscle tone was found in 90% at age 6 months and 51% at age 24 months. While almost half (49%) had normal scores for neurocognitive and language skills, 17% had mildly delayed and 15% had severe delayed scores. Likewise, in psychomotor testing, while 46% had normal scores, 23% and 31% scored as mildly delayed and severely delayed, respectively. Autism was present in 7%. Studies of brain maturation using MRI show delayed structural brain development and other abnormalities that may lead to long-term neurologic complications ⁶⁵.

In a retrospective follow-up study of 55 children survivors with scimitar syndrome followed at one center, a high rate of respiratory complications was observed. All (100%) of the children had right lung hypoplasia of varying degrees of severity. The median duration of follow-up was 7.2 years. Pulmonary infections were reported in 38%, and 43% of children reported wheezing episodes during the last 12 months of follow-up. A restrictive pattern of lung function was observed in the majority of patients, likely related to right-sided lung hypoplasia. Lower total lung capacity values were seen in children with the infantile form of scimitar syndrome, possibly reflective of the severity of pulmonary hypoplasia in these children ⁶⁶.

Right-sided hypoplasia, typically secondary to right sided congenital diaphragmatic hernia, seems to carry a higher mortality. This is likely due to higher risk of recurrent herniation, increased risk of pulmonary complications, requiring pulmonary vasodilator therapy and tracheostomy. However, no differences in neurodevelopmental outcomes was found ⁶⁷.

A minimum lung volume of 45% compared with age-matched control subjects has been shown to be a predictor of survival in neonates with diaphragmatic hernia treated with extracorporeal membrane oxygenation (ECMO). Similarly, a functional residual capacity of 12.3 mL/kg, about one half the normal capacity, has been thought to be a predictor of survival in pulmonary hypoplasia with congenital diaphragmatic hernia.

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Human lungs

The lungs are soft, spongy, cone-shaped organs in the thoracic (chest) cavity. The lungs consist largely of air tubes and spaces. The balance of the lung tissue, its stroma, is a framework of connective tissue containing many elastic fibers. As a result, the lungs are light, soft, spongy, elastic organs that each weigh only about 0.6 kg (1.25 pounds). The elasticity of healthy lungs helps to reduce the effort of breathing.

The left and right lungs are situated in the left and right pleural cavities inside the thoracic cavity. They are separated from each other by the heart and other structures of the mediastinum, which divides the thoracic cavity into two anatomically distinct chambers. As a result, if trauma causes one lung to collapse, the other may remain expanded. Below the lungs, a thin, dome-shaped muscle called the diaphragm separates the chest from the abdomen. When you breathe, the diaphragm moves up and down, forcing air in and out of the lungs. The thoracic cage encloses the rest of the lungs.

Each lung occupies most of the space on its side of the thoracic cavity. A bronchus and some large blood vessels suspend each lung in the cavity. These tubular structures enter the lung on its medial surface.

Parietal refers to a membrane attached to the wall of a cavity; visceral refers to a membrane that is deeper—toward the interior—and covers an internal organ, such as a lung. Within the thoracic (chest) cavity, the compartments that contain the lungs, on either side of the mediastinum, are lined with a membrane called the parietal pleura. A similar membrane, called the visceral pleura, covers each lung.

The parietal and visceral pleural membranes are separated only by a thin film of watery fluid (serous fluid), which they secrete. Although no actual space normally exists between these membranes, the potential space between them is called the pleural cavity.

A thin lining layer called the pleura surrounds the lungs. The pleura protects your lungs and helps them slide back and forth against the chest wall as they expand and contract during breathing. A layer of serous membrane, the visceral pleura, firmly attaches to each lung surface and folds back to become the parietal pleura. The parietal pleura, in turn, borders part of the mediastinum and lines the inner wall of the thoracic cavity and the superior surface of the diaphragm.

Figure 1. Lungs anatomy

In certain conditions, the pleural cavities may fill with air (pneumothorax), blood (hemothorax), or pus. Air in the pleural cavities, most commonly introduced in a surgical opening of the chest or as a result of a stab or gunshot wound, may cause the lungs to collapse. This collapse of a part of a lung, or rarely an entire lung, is called atelectasis. The goal of treatment is the evacuation of air (or blood) from the pleural space, which allows the lung to reinflate. A small pneumothorax may resolve on its own, but it is oft en necessary to insert a chest tube to assist in evacuation.

The thoracic (chest) cavity is divided by a thick wall called the mediastinum. This is the region between the lungs, extending from the base of the neck to the diaphragm. It is occupied by the heart, the major blood vessels connected to it, the esophagus, the trachea and bronchi, and a gland called the thymus.

Each lung is a blunt cone with the tip, or apex, pointing superiorly. The apex on each side extends into the base of the neck, superior to the first rib. The broad concave inferior portion, or base, of each lung rests on the superior surface of the diaphragm.

On the medial (mediastinal) surface of each lung is an indentation, the hilum, through which blood vessels, bronchi, lymphatic vessels, and nerves enter and exit the lung. Collectively, these structures attach the lung to the mediastinum and are called the root of the lung. The largest components of this root are the pulmonary artery and veins and the main (primary) bronchus. Because the heart is tilted slightly to the left of the median plane of the thorax, the left and right lungs differ slightly in shape and size.

Within each root and located in the hilum are:

• a pulmonary artery,
• two pulmonary veins,
• a main bronchus,
• bronchial vessels,
• nerves, and
• lymphatics.

Generally, the pulmonary artery is superior at the hilum, the pulmonary veins are inferior, and the bronchi are somewhat posterior in position. On the right side, the lobar bronchus to the superior lobe branches from the main bronchus in the root, unlike on the left where it branches within the lung itself, and is superior to the pulmonary artery.

Figure 2. Hilum (roots) of the lungs

Several deep fissures divide the two lungs into different patterns of lobes.

• The left lung is divided into two lobes, the superior lobe and the inferior lobe, by the oblique fissure. The left lung is somewhat smaller than the right and has a cardiac notch, a deviation in its anterior border that accommodates the heart.
• The right lung is partitioned into three lobes, the superior, middle, and inferior lobes, by the oblique and horizontal fissures.

Each lung lobe is served by a lobar (secondary) bronchus and its branches. Each of the lobes, in turn, contains a number of bronchopulmonary segments separated from one another by thin partitions of dense connective tissue. Each segment receives air from an individual segmental (tertiary) bronchus. There are approximately ten bronchopulmonary segments arranged in similar, but not identical, patterns in each of the two lungs.

The bronchopulmonary segments have clinical significance in that they limit the spread of some diseases within the lung, because infections do not easily cross the connective tissue partitions between them. Furthermore, because only small veins span these partitions, surgeons can neatly remove segments without cutting any major blood vessels.

The smallest subdivision of the lung that can be seen with the naked eye is the lobule. Appearing on the lung surface as hexagons ranging from the size of a pencil eraser to the size of a penny, each lobule is served by a bronchiole and its branches. In most city dwellers and in smokers, the connective tissue that separates the individual lobules is blackened with carbon.

Each lung has a half-cone shape, with a base, apex, two surfaces, and three borders.

• The base sits on the diaphragm.
• The apex projects above rib I and into the root of the neck.
• The two surfaces-the costal surface lies immediately adjacent to the ribs and intercostal spaces of the thoracic wall. The mediastinal surface lies against the mediastinum anteriorly and the vertebral column posteriorly and contains the comma-shaped hilum of the lung, through which structures enter and leave.
• The three borders-the inferior border of the lung is sharp and separates the base from the costal surface. The anterior and posterior borders separate the costal surface from the medial surface. Unlike the anterior and inferior borders, which are sharp, the posterior border is smooth and rounded.

Lung anatomy

Right lung

The right lung has three lobes and two fissures. Normally, the lobes are freely movable against each other because they are separated, almost to the hilum, by invaginations of visceral pleura. These invaginations form the fissures:

• The oblique fissure separates the inferior lobe (lower lobe) from the superior lobe and the middle lobe of the right lung.
• The horizontal fissure separates the superior lobe (upper lobe) from the middle lobe.

The approximate position of the oblique fissure on a patient, in quiet respiration, can be marked by a curved line on the thoracic wall that begins roughly at the spinous process of the vertebra TIV level of the spine, crosses the fifth interspace laterally, and then follows the contour of rib VI anteriorly.

The horizontal fissure follows the fourth intercostal space from the sternum until it meets the oblique fissure as it crosses rib V.

The orientations of the oblique and horizontal fissures determine where clinicians should listen for lung sounds from each lobe. The largest surface of the superior lobe is in contact with the upper part of the anterolateral wall and the apex of this lobe proj ects into the root of the neck. The surface of the middle lobe lies mainly adjacent to the lower anterior and lateral wall. The costal surface of the inferior lobe is in contact with the posterior and inferior walls.

The medial surface of the right lung lies adjacent to a number of important structures in the mediastinum and the root of the neck. These include the:

• heart,
• inferior vena cava,
• superior vena cava,
• azygos vein, and
• esophagus.

The right subclavian artery and vein arch over and are related to the superior lobe of the right lung as they pass over the dome of the cervical pleura and into the axilla.

Left lung

The left Iung is smaller than the right lung and has two lobes separated by an oblique fissure. The oblique fissure of the left lung is slightly more oblique than the corresponding fissure of the right lung. During quiet respiration, the approximate position of the left oblique fissure can be marked by a curved line on the thoracic wall that begins between the spinous processes of vertebrae T III and T IV, crosses the fifth interspace laterally, and follows the contour of rib VI  anteriorly.

As with the right lung, the orientation of the oblique fissure determines where to listen for lung sounds from each lobe. The largest surface of the superior lobe is in contact with the upper part of the anterolateral wall, and the apex of this lobe proj ects into the root of the neck. The costal surface of the inferior lobe is in contact with the posterior and inferior walls.

The inferior portion o f the medial surface of the left lung, unlike the right lung, is notched because of the heart’s projection into the left pleural cavity from the middle mediastinum. From the anterior border of the lower part of the superior lobe a tongue-like extension (the lingula of the left lung) projects over the heart bulge.

The medial surface of the left lung lies adjacent to a number of important structures in the mediastinum and root of the neck. These include the:

• heart,
• aortic arch,
• thoracic aorta, and
• esophagus.

The left subclavian artery and vein arch over and are related to the superior lobe of the left lung as they pass over the dome of the cervical pleura and into the axilla.

Bronchial tree

The trachea is a flexible tube that extends from vertebral level C VI (cervical spine C6) in the lower neck to vertebral level T IV /V (thoracic spine T4-T5) in the
mediastinum where it bifurcates into a right and a left main bronchus. The trachea is held open by C-shaped transverse cartilage rings embedded in its wall the open part of the C facing posteriorly. The lowest tracheal ring has a hook-shaped structure, the carina, that projects backwards in the midline between the origins of the two main bronchi. The posterior wall of the trachea is composed mainly of smooth muscle. Each main bronchus enters the root of a lung and passes  through the hilum into the lung itself. The right main bronchus is wider and takes a more vertical course through the root and hilum than the left main bronchus. Therefore, inhaled foreign bodies tend to lodge more frequently on the right side than on the left.

The bronchial tree consists of branched airways leading from the trachea to the microscopic air sacs in the lungs (Figure 3, 5 and 6). Its branches begin with the right and left main (primary) bronchi, which arise from the trachea at the level of the fifth thoracic vertebra. Each bronchus enters its respective lung. A short distance from its origin, each main bronchus divides into lobar (secondary) bronchi. The lobar bronchi branch into segmental (tertiary) bronchi, which supply bronchopulmonary segments. Within each bronchopulmonary segment, the segmental bronchi give rise to multiple generations of divisions of increasingly finer tubes and, ultimately, to bronchioles , which further subdivide to terminal bronchioles, respiratory bronchioles, and finally to very thin tubes called alveolar ducts. These ducts lead to thin-walled outpouchings called alveolar sacs. Alveolar sacs lead to smaller, microscopic air sacs called alveoli (singular, alveolus), which lie within capillary networks (Figure 6). The alveoli are the sites of gas exchange between the inhaled air and the bloodstream.

The structure of a bronchus is similar to that of the trachea, but the tubes that branch from it have less cartilage in their walls, and the bronchioles lack cartilage. As the cartilage diminishes, a layer of smooth muscle surrounding the tube becomes more prominent. This muscular layer persists even in the smallest  bronchioles, but only a few muscle cells are associated with the alveolar ducts.

The absence of cartilage in the bronchioles allows their diameters to change in response to contraction of the smooth muscle in their walls, similar to what happens with arterioles of the cardiovascular system. Part of the “fight-or-flight” response, triggered by the sympathetic nervous system, is bronchodilation, in which the smooth muscle relaxes and the airways become wider and allow more airflow. The opposite, bronchoconstriction, occurs when the smooth muscle contracts and it becomes difficult to move air in and out of the lungs. Bronchoconstriction can occur with allergies. Asthma is an extreme example of bronchoconstriction.

The mucous membranes of the bronchial tree continue to filter the incoming air, and the many branches of the tree distribute the air to alveoli throughout the lungs. The alveoli, in turn, provide a large surface area of thin simple squamous epithelial cells through which gases are easily exchanged. Oxygen diffuses from the alveoli into the blood in nearby capillaries, and carbon dioxide diffuses from the blood into the alveoli.

Figure 3. Bronchial tree of the lungs

Bronchopulmonary segments

A bronchopulmonary segment is the area of lung supplied by a segmental bronchus and its accompanying pulmonary artery branch. Tributaries of the pulmonary vein tend to pass intersegmentally between and around the margins of segments. Each bronchopulmonary segment is shaped like an irregular cone, with the apex at the origin of the segmental bronchus and the base projected peripherally onto the surface of the lung.

A bronchopulmonary segment is the smallest functionally independent region of a lung and the smallest area of lung that can be isolated and removed without affecting adjacent regions.

There are ten bronchopulmonary segments in each lung (Figure 4) ; some of them fuse in the left lung.

Figure 4. Bronchopulmonary segments

Lung Alveoli

Each human lung is a spongy mass composed of 150 million little sacs, the alveoli. These provide about 70 m2, per lung, of gas-exchange surface—about equal to the floor area of a handball court or a room about 8.4 m (25 ft) square.

An alveolus is a pouch about 0.2 to 0.5 mm in diameter. Thin, broad cells called squamous (type I) alveolar cells cover about 95% of the alveolar surface area. Their thinness allows for rapid gas diffusion between the air and blood. The other 5% is covered by round to cuboidal great (type II) alveolar cells. Even though they cover less surface area, these considerably outnumber the squamous alveolar cells.

Great (type II) alveolar cells have two functions:

1. They repair the alveolar epithelium when the squamous cells are damaged; and
2. They secrete pulmonary surfactant, a mixture of phospholipids and protein that coats the alveoli and smallest bronchioles and prevents the bronchioles from collapsing when one exhales.

The most numerous of all cells in the lung are alveolar macrophages (dust cells), which wander the lumens of the alveoli and the connective tissue between them. These cells keep the alveoli free of debris by phagocytizing dust particles that escape entrapment by mucus in the higher parts of the respiratory tract. In lungs that are infected or bleeding, the macrophages also phagocytize bacteria and loose blood cells. As many as 100 million alveolar macrophages perish each day as they ride up the mucociliary escalator to be swallowed and digested, thus ridding the lungs of their load of debris.

Each alveolus is surrounded by a web of blood capillaries supplied by small branches of the pulmonary artery. The barrier between the alveolar air and blood, called the respiratory membrane, consists only of the squamous alveolar cell, the squamous endothelial cell of the capillary, and their shared basement membrane. These have a total thickness of only 0.5 μm, just 1/15 the diameter of a single red blood cell.

It is very important to prevent fluid from accumulating in the alveoli, because gases diffuse too slowly through liquid to sufficiently aerate the blood. Except for a thin film of moisture on the alveolar wall, the alveoli are kept dry by the absorption of excess liquid by the blood capillaries. The mean blood pressure in these capillaries is only 10 mm Hg compared to 30 mm Hg at the arterial end of the average capillary elsewhere. This low blood pressure is greatly overridden by the oncotic pressure that retains fluid in the capillaries, so the osmotic uptake of water overrides filtration and keeps the alveoli free of fluid. The lungs also have a more extensive lymphatic drainage than any other organ in the body. The low capillary blood pressure also prevents rupture of the delicate respiratory membrane.

Figure 5. Lungs alveoli

Figure 6. Pulmonary Alveoli (microscopic view)

Note: (a) Clusters of alveoli and their blood supply. (b) Structure of an alveolus. (c) Structure of the respiratory membrane.

What Controls Your Breathing ?

A respiratory control center at the base of your brain controls your breathing. This center sends ongoing signals down your spine and to the muscles involved in breathing.

These signals ensure your breathing muscles contract (tighten) and relax regularly. This allows your breathing to happen automatically, without you being aware of it.

To a limited degree, you can change your breathing rate, such as by breathing faster or holding your breath. Your emotions also can change your breathing. For example, being scared or angry can affect your breathing pattern.

Your breathing will change depending on how active you are and the condition of the air around you. For example, you need to breathe more often when you do physical activity. In contrast, your body needs to restrict how much air you breathe if the air contains irritants or toxins.

To adjust your breathing to changing needs, your body has many sensors in your brain, blood vessels, muscles, and lungs.

Sensors in the brain and in two major blood vessels (the carotid artery and the aorta) detect carbon dioxide or oxygen levels in your blood and change your breathing rate as needed.

Sensors in the airways detect lung irritants. The sensors can trigger sneezing or coughing. In people who have asthma, the sensors may cause the muscles around the airways in the lungs to contract. This makes the airways smaller.

Sensors in the lungs alveoli (air sacs) can detect fluid buildup in the lung tissues. These sensors are thought to trigger rapid, shallow breathing.

Sensors in your joints and muscles detect movement of your arms or legs. These sensors may play a role in increasing your breathing rate when you’re physically active.

Lung disease

Asthma is a chronic disease that affects your airways ¹. Your airways are tubes that carry air in and out of your lungs. If you have asthma, the inside walls of your airways become sore and swollen. That makes them very sensitive, and they may react strongly to things that you are allergic to or find irritating. When your airways react, they get narrower and your lungs get less air.

Symptoms of asthma include

• Wheezing
• Coughing, especially early in the morning or at night
• Chest tightness
• Shortness of breath

Not all people who have asthma have these symptoms. Having these symptoms doesn’t always mean that you have asthma. Your doctor will diagnose asthma based on lung function tests, your medical history, and a physical exam. You may also have allergy tests.

When your asthma symptoms become worse than usual, it’s called an asthma attack. Severe asthma attacks may require emergency care, and they can be fatal.

Asthma is treated with two kinds of medicines: quick-relief medicines to stop asthma symptoms and long-term control medicines to prevent symptoms.

Asthma – quick-relief drugs

Asthma quick-relief medicines work fast to control asthma symptoms ². You take them when you are coughing, wheezing, having trouble breathing, or having an asthma attack. They are also called rescue drugs. These medicines are called “bronchodilators” because they open (dilate) and help relax the muscles of your airways (bronchi) ².

You and your doctor can make a plan for the quick-relief drugs that work for you. This plan will include when you should take them and how much you should take.

Plan ahead. Make sure you do not run out. Take enough with you when you travel.

Short-acting Beta-agonists

Short-acting beta-agonists are the most common quick-relief drugs for treating asthma attacks.

They can be used just before exercising to help prevent asthma symptoms caused by exercise. They work by relaxing the muscles of your airways, and this lets you breathe better during an attack.

Tell your doctor if you are using quick-relief medicines twice a week or more to control your asthma symptoms. Your asthma may not be under control, and your doctor may need to change your dose of daily control drugs.

Some quick-relief asthma medicines include ²:

• Albuterol (ProAir HFA, Proventil HFA, Ventolin HFA)
• Levalbuterol (Xopenex HFA)
• Metaproterenol
• Terbutaline

Quick-relief asthma medicines may cause these side effects:

• Anxiety.
• Tremor (your hand or another part of your body may shake).
• Restlessness.
• Headache.
• Fast and irregular heartbeats. Call your doctor right away if you have this side effect.

Oral Steroids

Your doctor might prescribe oral steroids when you have an asthma attack that is not going away. These are medicines that you take by mouth as pills, capsules, or liquids.

Oral steroids are not quick-relief medicines, but are often given for 7 to 14 days when your symptoms flare-up.

Oral steroids include:

• Prednisone
• Prednisolone
• Methylprednisolone.

Asthma – control drugs

Control medicines for asthma are drugs you take to control your asthma symptoms ³. You must take them every day for them to work. You and your doctor can make a plan for the medicines that work for you. This plan will include when you should take them and how much you should take.

You may need to take these medicines for at least a month before you start to feel better.

Take the medicines even when you feel OK. Take enough with you when you travel. Plan ahead. Make sure you do not run out.

Inhaled Corticosteroids

Inhaled corticosteroids prevent your airways from swelling in order to help keep your asthma symptoms away.

Inhaled steroids are used with a metered dose inhaler (MDI) and spacer. Or they may be used with a dry powder inhaler.

You should use an inhaled steroid every day, even if you do not have symptoms.

After you use it, rinse your mouth with water, gargle, and spit it out.

If your child cannot use an inhaler, your doctor will give you a drug to use with a nebulizer. This machine turns liquid medicine into a spray so your child can breathe the medicine in.

Long-acting Beta-agonist Inhalers

These medicines relax the muscles of your airways to help keep your asthma symptoms away.

Normally, you use these medicines only when you are using an inhaled steroid drug and you still have symptoms. DO NOT take these long-acting medicines alone.

Use this medicine every day, even if you do not have symptoms.

Combination Therapy

Your doctor may ask you to take both a steroid drug and a long-acting beta-agonist drug.

It may be easier to use an inhaler that has both drugs in them.

Leukotriene Modifiers

These medicines are used to prevent asthma symptoms. They come in tablet or pill form and can be used together with a steroid inhaler.

Cromolyn

Cromolyn is a medicine that may prevent asthma symptoms. It can be used in a nebulizer, so it may be easy for young children to take.

Bronchitis

Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs ⁴. This swelling narrows the airways, which makes it harder to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. It can also cause shortness of breath, wheezing, a low fever, and chest tightness. Acute means the symptoms have been present only for a short time.

There are two main types of bronchitis:

• Acute bronchitis and
• Chronic bronchitis.

Acute bronchitis

When acute bronchitis occurs, it almost always comes after having a cold or flu-like illness ⁵. The bronchitis infection is caused by a virus. At first, it affects your nose, sinuses, and throat. Then it spreads to the airways that lead to your lungs.

Some symptoms of acute bronchitis are:

• Chest discomfort
• Cough that produces mucus — the mucus may be clear or yellow-green
• Fatigue
• Fever — usually low-grade
• Shortness of breath that gets worse with activity
• Wheezing, in people with asthma

Even after acute bronchitis has cleared, you may have a dry, nagging cough that lasts for 1 to 4 weeks.

Sometimes it can be hard to know if you have pneumonia or bronchitis. If you have pneumonia, you are more likely to have a high fever and chills, feel sicker, or be more short of breath.

How is acute bronchitis diagnosed ?

Your health care provider will listen to the breathing sounds in your lungs with a stethoscope. Your breathing may sound abnormal or rough.

Tests may include:

• Chest x-ray, if your provider suspects pneumonia
• Pulse oximetry, a painless test that helps determine the amount of oxygen in your blood by using a device placed on the end of your finger

Treatment of acute bronchitis 

Most people DO NOT need antibiotics for acute bronchitis ⁵. The infection will almost always go away on its own within 1 week. Doing these things may help you feel better:

• Drink plenty of fluids.
• If you have asthma or another chronic lung condition, use your inhaler.
• Get plenty of rest.
• Take aspirin or acetaminophen if you have a fever. DO NOT give aspirin to children.
• Breathe moist air by using a humidifier or steaming up the bathroom.

Certain medicines that you can buy without a prescription can help break up or loosen mucus. Look for the word “guaifenesin” on the label. Ask the pharmacist for help finding it.

If your symptoms do not improve or if you are wheezing, your provider may prescribe an inhaler to open your airways.

If your provider thinks you also have bacteria in your airways, they may prescribe antibiotics. This medicine will only get rid of bacteria, not viruses.

Your provider may also prescribe corticosteroid medicine to reduce swelling in your lungs.

If you have the flu and it is caught in the first 48 hours after getting sick, your provider might also prescribe antiviral medicine.

Other tips include:

• DO NOT smoke.
• Avoid secondhand smoke and air pollution.
• Wash your hands (and your children’s hands) often to avoid spreading viruses and other germs.

Outlook (Prognosis) of acute bronchitis

Except for the cough, symptoms usually go away in 7 to 10 days if you do not have a lung disorder.

When to see a your doctor

Call your healthcare provider if you:

• Have a cough on most days, or have a cough that keeps returning
• Are coughing up blood
• Have a high fever or shaking chills
• Have a low-grade fever for 3 or more days
• Have thick, yellow-green mucus, especially if it has a bad smell
• Feel short of breath or have chest pain
• Have a chronic illness, like heart or lung disease

Chronic bronchitis

Chronic bronchitis is one type of COPD (chronic obstructive pulmonary disease). The inflamed bronchial tubes produce a lot of mucus. This leads to coughing and difficulty breathing. Cigarette smoking is the most common cause. Breathing in air pollution, fumes, or dust over a long period of time may also cause it.

To diagnose chronic bronchitis, your doctor will look at your signs and symptoms and listen to your breathing. You may also have other tests.

Chronic bronchitis is a long-term condition that keeps coming back or never goes away completely. If you smoke, it is important to quit. Treatment can help with your symptoms. It often includes medicines to open your airways and help clear away mucus. You may also need oxygen therapy. Pulmonary rehabilitation may help you manage better in daily life.

Chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a common lung disease. Having COPD makes it hard to breathe.

There are two main forms of chronic obstructive pulmonary disease (COPD) ⁶:

• Chronic bronchitis, which involves a long-term cough with mucus
• Emphysema, which involves damage to the lungs over time

Most people with chronic obstructive pulmonary disease (COPD) have a combination of both conditions.

Causes of chronic obstructive pulmonary disease (COPD)

Smoking is the main cause of COPD. The more a person smokes, the more likely that person will develop COPD. But some people smoke for years and never get COPD.

In rare cases, nonsmokers who lack a protein called alpha-1 antitrypsin can develop emphysema.

Other risk factors for COPD are:

• Exposure to certain gases or fumes in the workplace
• Exposure to heavy amounts of secondhand smoke and pollution
• Frequent use of a cooking fire without proper ventilation.

How to prevent chronic obstructive pulmonary disease (COPD)

• Not smoking prevents most chronic obstructive pulmonary disease (COPD). Ask your provider about quit-smoking programs. Medicines are also available to help you stop smoking.

Symptoms of chronic obstructive pulmonary disease (COPD)

Symptoms may include any of the following:

• Cough, with or without mucous
• Fatigue
• Many respiratory infections
• Shortness of breath (dyspnea) that gets worse with mild activity
• Trouble catching one’s breath
• Wheezing

Because the symptoms develop slowly, some people may not know that they have COPD.

Chronic obstructive pulmonary disease (COPD) diagnosis

The best test for COPD is a lung function test called spirometry. This involves blowing out as hard as possible into a small machine that tests lung capacity. The results can be checked right away.

Using a stethoscope to listen to the lungs can also be helpful. But sometimes, the lungs sound normal, even when a person has COPD.

Imaging tests of the lungs, such as x-rays and CT scans, can be helpful. With an x-ray, the lungs may look normal, even when a person has COPD. A CT scan will usually show signs of COPD.

Sometimes, a blood test called arterial blood gas may be done to measure the amounts of oxygen and carbon dioxide in the blood.

Treatment for chronic obstructive pulmonary disease (COPD)

There is no cure for COPD. But there are many things you can do to relieve symptoms and keep the disease from getting worse.

If you smoke, now is the time to quit. This is the best way to slow lung damage.

Medicines used to treat COPD include:

• Inhalers (bronchodilators) COPD — quick-relief drugs to help open the airways
• Inhaled COPD control drugs or oral steroids to reduce lung inflammation
• Anti-inflammatory drugs to reduce swelling in the airways
• Certain long-term antibiotics

In severe cases or during flare-ups, you may need to receive:

• Steroids by mouth or through a vein (intravenously)
• Bronchodilators through a nebulizer
• Oxygen therapy
• Assistance from a machine to help breathing by using a mask, BiPAP, or through the use of an endotracheal tube

Your health care provider may prescribe antibiotics during symptom flare-ups, because an infection can make COPD worse.

You may need oxygen therapy at home if you have a low level of oxygen in your blood.

Pulmonary rehabilitation does not cure COPD. But it can teach you to breathe in a different way so you can stay active and feel better.

Living with chronic obstructive pulmonary disease (COPD)

You can do things every day to keep COPD from getting worse, protect your lungs, and stay healthy.

Walk to build up strength:

• Ask the provider or therapist how far to walk.
• Slowly increase how far you walk.
• Avoid talking if you get short of breath when you walk.
• Use pursed lip breathing when you breathe out, to empty your lungs before the next breath.

Things you can do to make it easier for yourself around the home include:

• Avoid very cold air or very hot weather
• Make sure no one smokes in your home
• Reduce air pollution by not using the fireplace and getting rid of other irritants
• Manage stress in your mood

Eat healthy foods, including fish, poultry, and lean meat, as well as fruits and vegetables. If it is hard to keep your weight up, talk to a provider or dietitian about eating foods with more calories.

Surgery may be used to treat COPD. Only a few people benefit from these surgical treatments:

Surgery to remove parts of the diseased lung, which can help less-diseased parts work better in some people with emphysema. Lung transplant for a small number of very severe cases

Outlook (Prognosis) of chronic obstructive pulmonary disease (COPD)

COPD is a long-term (chronic) illness. The disease will get worse more quickly if you do not stop smoking.

If you have severe COPD, you will be short of breath with most activities. You may be admitted to the hospital more often.

Talk with your provider about breathing machines and end-of-life care as the disease progresses.

Possible Complications of chronic obstructive pulmonary disease (COPD)

With COPD, you may have other health problems such as:

• Irregular heartbeat (arrhythmia)
• Need for breathing machine and oxygen therapy
• Right-sided heart failure or cor pulmonale (heart swelling and heart failure due to chronic lung disease)
• Pneumonia
• Pneumothorax
• Severe weight loss and malnutrition
• Thinning of the bones (osteoporosis)
• Debilitation
• Increased anxiety

Pulmonary embolism (PE)

A pulmonary embolism is a sudden blockage in a lung artery ⁷. The cause is usually a blood clot in the leg called a deep vein thrombosis (DVT) that breaks loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can cause:

• Permanent damage to the affected lung
• Low oxygen levels in your blood
• Damage to other organs in your body from not getting enough oxygen

If a clot is large, or if there are many clots, pulmonary embolism can cause death.

Half the people who have pulmonary embolism have no symptoms. If you do have symptoms, they can include shortness of breath, chest pain or coughing up blood. Symptoms of a blood clot include warmth, swelling, pain, tenderness and redness of the leg. The goal of treatment is to break up clots and help keep other clots from forming.

Causes of pulmonary embolism

A pulmonary embolus is most often caused by a blood clot that develops in a vein outside the lungs. The most common blood clot is one in a deep vein of the thigh or in the pelvis (hip area). This type of clot is called a deep vein thrombosis. The blood clot breaks off and travels to the lungs where it lodges.

Less common causes include air bubbles, fat droplets, amniotic fluid, or clumps of parasites or tumor cells.

You are more likely to get this condition if you or your family has a history of blood clots or certain clotting disorders.

A pulmonary embolus may occur ⁸:

• After childbirth
• After heart attack, heart surgery, or stroke
• After severe injuries, burns, or fractures of the hips or thigh bone
• After surgery, most commonly bone, joint, or brain surgery
• During or after a long plane or car ride
• If you have cancer
• If you take birth control pills or estrogen therapy
• Long-term bed rest or staying in one position for a long time

Disorders that may lead to blood clots include ⁸:

• Diseases of the immune system that make it harder for the blood to clot.
• Inherited disorders that make the blood more likely to clot. One such disorder is antithrombin III deficiency.

Prevention of pulmonary embolism

Blood thinners may be prescribed to help prevent deep vein thrombosis (DVT) in people at high risk, or those who are undergoing high-risk surgery.

If you had a deep vein thrombosis, your provider will prescribe pressure stockings. Wear them as instructed. They will improve blood flow in your legs and reduce your risk of blood clots.

Moving your legs often during long plane trips, car trips, and other situations in which you are sitting or lying down for long periods can also help prevent deep vein thrombosis. People at very high risk for blood clots may need shots of a blood thinner called heparin when they take a flight that lasts longer than 4 hours.

Do not smoke. If you smoke, quit. Women who are taking estrogen must stop smoking. Smoking increases your risk of developing blood clots.

Symptoms of pulmonary embolism

Main symptoms of a pulmonary embolism include chest pain that may be any of the following:

• Under the breastbone or on one side
• Sharp or stabbing
• Burning, aching, or a dull, heavy sensation
• Often gets worse with deep breathing
• You may bend over or hold your chest in response to the pain

Other symptoms may include:

• Bluish skin (cyanosis)
• Dizziness, lightheadedness, or fainting
• Fast breathing or wheezing
• Fast heart rate
• Feeling anxious
• Leg pain, redness, or swelling
• Low blood pressure
• Sudden cough, possibly coughing up blood or bloody mucus
• Shortness of breath that starts suddenly
• Sweating, clammy skin.

How is pulmonary embolism diagnosed ?

The health care provider will perform a physical exam and ask about your symptoms and medical history.

The following lab tests may be done to see how well your lungs are working:

• Arterial blood gases
• Pulse oximetry

The following imaging tests can help determine where the blood clot is located:

• Chest x-ray
• CT angiogram of the chest
• Pulmonary ventilation/perfusion scan, also called a V/Q scan
• Pulmonary angiogram

Other tests that may be done include:

• Chest CT scan
• D-dimer blood test
• Doppler ultrasound exam of the legs
• Echocardiogram (ECG)

Blood tests may be done to check if you have an increased chance of blood clotting, including:

• Antiphospholipid antibodies
• Genetic testing to look for changes that make you more likely to develop blood clots
• Lupus anticoagulant
• Protein C and protein S levels

Treatment for pulmonary embolism

A pulmonary embolus requires treatment right away. You may need to stay in the hospital:

• You will receive medicines to thin the blood and make it less likely your blood will form more clots.
• In cases of severe, life-threatening pulmonary embolism, treatment may involve dissolving the clot. This is called thrombolytic therapy. You will receive medicines to dissolve the clot.

Whether or not you need to stay in the hospital, you will likely need to take medicines at home to thin the blood:

• You may be given pills to take or you may need to give yourself injections.
• For some medicines, you will need blood tests to monitor your dosage.
• How long you need to take these medicines depends mostly on the cause and size of your blood clot.
• Your provider will talk to you about the risk of bleeding problems when you take these medicines.

If you cannot take blood thinners, your doctor may suggest surgery to place a device called an inferior vena cava filter (IVC filter). This device is placed in the main vein in your belly. It keeps large clots from traveling into the blood vessels of the lungs. Sometimes, a temporary filter can be placed and removed later.

Outlook (Prognosis) of pulmonary embolism

How well a person recovers from a pulmonary embolus can be hard to predict. It often depends on:

• What caused the problem in the first place (for example, cancer, major surgery, or an injury)
• The size of the blood clot in the lungs
• If the blood clot dissolves over time

Some people can develop long-term heart and lung problems.

Death is possible in people with a severe pulmonary embolism.

Lungs infection

Pneumonia is an infection in one or both of the lungs. Many germs, such as bacteria, viruses, and fungi, can cause pneumonia. You can also get pneumonia by inhaling a liquid or chemical. People most at risk are older than 65 or younger than 2 years of age, or already have health problems.

Symptoms of pneumonia vary from mild to severe. See your doctor promptly if you

• Have a high fever
• Have shaking chills
• Have a cough with phlegm that doesn’t improve or gets worse
• Develop shortness of breath with normal daily activities
• Have chest pain when you breathe or cough
• Feel suddenly worse after a cold or the flu

Your doctor will use your medical history, a physical exam, and lab tests to diagnose pneumonia. Treatment depends on what kind you have. If bacteria are the cause, antibiotics should help. If you have viral pneumonia, your doctor may prescribe an antiviral medicine to treat it.

Preventing pneumonia is always better than treating it. Vaccines are available to prevent pneumococcal pneumonia and the flu. Other preventive measures include washing your hands frequently and not smoking.

Lung nodule

A lung nodule is also called a spot on your lung (pulmonary nodule). It is usually round or oval in shape. They are easy to find but can be hard to diagnose. Nodules are found in 1 out of every 4 chest CT scans. Most nodules (more than 90%) are benign and not cancerous ⁹. Benign or non-cancerous nodules can be caused by previous infections or old surgery scars.

Nodules need to be examined and watched closely because they might be a small cancer. Finding cancers early when they are small and curable, is the goal of a screening program. Almost eighty percent of people who have a small lung cancer (1 cm in size, about ½ inch) surgically removed, live at least five years after the diagnosis and are considered cured. Unfortunately people with larger lung cancer have a lower survival rate. Early detection is the key to a better outcome.

What are the symptoms of a lung nodule ?

Nearly 90% of all lung nodules are discovered by accident ⁹. Usually they are seen on a chest x-rays or a CT scan that was performed for other reasons. Symptoms are few if any, but may include those similar to a chest cold or a mild flu.

How is a lung nodule examined ?

If a lung nodule is considered highly suspicious for lung cancer based on its size, shape and appearance on chest x-ray or CT scan as well as considering other risk factors such as your smoking history and family history of cancer, it will need to be biopsied to determine if it is cancerous. The biopsy is a simple procedure of getting a sample from the pulmonary nodule for microscopic exam. It can be done surgically, bronchoscopically and by placing a needle thru the chest wall under radiographic guidance.

The bronchoscope approach is an outpatient procedure without any cutting, sutures or sticking needles thru the chest wall. After heavy sedation and numbing of mouth and throat, the bronchoscope is inserted in your airways and is guided to the lung nodule. A sample is taken and immediately examined by a pathologist (a doctor who identifies diseases by studying cells and tissue under a microscope).

The pathologist will determine if the nodule is cancerous or benign. If it is benign or not cancerous, your doctor will ask you to come back in the future to re-examine the spot with another X-ray. Your doctor will watch the nodule for any changes and catch it early if it becomes cancerous. If the nodule is cancerous, a few more samples will be taken or other tests performed to determine if the cancer has spread. The next steps will be discussed.

How are lung nodules treated ?

Benign or non-cancerous lung nodules do not need treatment.

In some cases your doctor may recommend annual chest imaging to see if a lung nodule grows or changes over time ¹⁰.

If a lung nodule is new or has changed in size, shape or appearance, your doctor may recommend further testing — such as a CT scan, positron emission tomography (PET) scan, bronchoscopy or tissue biopsy — to determine if it’s cancerous.

Lung cancer, if localized is usually removed surgically. If part of the cancer has spread to other parts of the body, you may need radiation and/or chemotherapy with or without surgery.

References

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