•Early consideration that leads to early evaluation and management of GI or hepatic disease is the best way of avoiding pulmonary complications.

—The diagnosis and management of respiratory disease are typically indicated for symptom management to mitigate the severity or progression of disease.

•The etiologic origins of pulmonary disease are varied and dependent on specific disease processes. In general, the common pathway is through an inflammatory process that leads to irritation, inflammation, impaired innate defense, infection, obstruction, and fibrosis.

•The epidemiology of pulmonary disease depends on the frequency and often the severity of GI or hepatic disease.

Pathophysiology

•Aspiration: Central nervous system immaturity or disease, swallowing dysfunction, or anatomic defects lead to foreign material being deposited in the airways and alveoli, which can impair innate defenses and/or cause direct injury of the parenchyma.

•GER: In spite of a strong association, the mechanism is not clearly understood; direct injury caused by acidic or nonacidic stomach contents has been proposed.

•α₁-antitrypsin deficiency: Loss of inhibition of neutrophil elastase leads to protease-mediated tissue destruction of the lungs; it is possibly expedited in cigarette smokers because cigarette smoke increases protease activity.

•Liver disease or cirrhosis: Different mechanisms are dependent on the underlying disease process, which could cause

—Direct lung injury from infections, increases in toxins or medications (directly or through immunosuppression), or hepatic infiltration

—Indirect lung injury via cirrhosis that could also lead to hepatopulmonary syndrome and/or portopulmonary hypertension

▪Hepatopulmonary syndrome is characterized by hypoxemia and dyspnea secondary to formation of intrapulmonary arteriovenous dilations. Portal hypertension is thought to lead to this because of either increased hepatic production or decreased hepatic clearance of vasodilators.

•Pancreatitis: The mechanism is typically an indirect consequence of the injury and/or inflammatory response to the pancreatitis.

Clinical Features

•Aspiration: Stridor, wheeze, cough, hoarseness, apnea, pneumonia

•GER: Stridor (in infants), brief resolved unexplained events (BRUE) (possibly), wheeze, cough, hoarseness, apnea, throat clearing, pneumonia, chest pain

•IBD: Cough, dyspnea, chest pain, wheeze

•α₁-antitrypsin deficiency: Wheeze, dyspnea, cough, exercise intolerance, chronic sputum production, and digital clubbing may develop in young adults, especially smokers. Lung disease does not develop during childhood.

•Liver disease or cirrhosis:

—Dyspnea, exercise intolerance, hypoxemia, digital clubbing, orthopnea, fatigue, and syncope

—Characteristic (but not pathognomonic) features include dyspnea (“platypnea”) and hypoxemia (“orthodeoxia”), which are worse in the upright position and are improved by lying supine because of a gravitational increase in blood flow through dilated vessels in the lung bases.

•Pancreatitis: Hypoxemia, painful deep inspiration, cough, and chest pain

•Aspiration

—Clinical evaluation by a feeding, speech, or occupational therapist

—Imaging studies

▪Direct evidence: Videofluoroscopic swallow study (also known as a modified barium swallow) and fiber-optic endoscopic evaluation of swallowing

▪Indirect evidence: Radionuclide salivagram, gastric-emptying scintigraphy with delayed imaging, chest radiography

—Direct: Lung biopsy

—Indirect: Computed tomography (CT) or magnetic resonance (MR) imaging, barium contrast studies, pulmonary function testing

•α₁-antitrypsin deficiency

—Direct: Genetic testing for alleles, serum testing for α₁-antitrypsin protein

—Indirect: CT, pulmonary function testing

•Liver disease or cirrhosis

—General testing: Liver function testing, γ-glutamyltransferase test; ultrasonography (US) and CT may show features of cirrhosis, such as hepatosplenomegaly and varices

—Specific testing

▪Hepatitides: Serum testing

▪Wilson disease: Ophthalmologic evaluation for Kayser-Fleischer rings; serum ceruloplasmin; urinary, serum, or hepatic copper levels

▪Portal hypertension: Ultrasonography, endoscopy, transient elastography

▪Hepatopulmonary syndrome: Bubble echocardiography, blood gas, cardiac catheterization

•Pancreatitis

—Amylase and lipase are useful for screening. US, endoscopy, CT, or MR imaging can be used to demonstrate anatomic causes and complications of pancreatitis.

Treatment/Management

•Aspiration

—Alternative method of feeding: Nasogastric tube, gastrostromy tube, gastrojejunostomy tube, jejunal tube

—Feeding therapy: Adjustment of thickness of food, avoidance of straws in older children, and use of special nipples in infants, as guided via video fluoroscopic swallow study

—Medical: Anticholinergic medication, glycopyrrolate may decrease aspiration of saliva

—Surgical: Partial ablation of salivary glands, Lindeman tracheoesophageal diversion

•GER

—Medical: H₂ antihistamine, proton pump inhibitor, reflux precautions, prokinetic agents, feedings that bypass the stomach (short term, nasojejunal; long term, gastrojejunal)

—Surgical: Nissen fundoplication

•IBD

—Dependent on type; immunosuppression, chemotherapy

—Augmentation therapy via infusion of α₁-antitrypsin

—Management of pulmonary complications: airway clearance therapies, bronchodilators, antibiotics as indicated

•Liver disease or cirrhosis

—Dependent on underlying disease

—Consider ursodiol and liver transplantation

—Specific management

▪Hepatitides

~B: Lamivudine, adefovir dipivoxil

~C: Peginterferon, ribavarin

▪Wilson disease: Chelating agents

▪Portal hypertension: Transjugular intrahepatic shunting

▪Hepatopulmonary syndrome: Transjugular intrahepatic shunting, inhaled nitric oxide, liver transplant

•Pancreatitis

—Partial or complete bowel rest

Prognosis of Pulmonary Disease

•Aspiration: Good if aspiration is well controlled

•GER: Good if GER is well controlled or resolved

•IBD: Dependent on control of IBD

•α₁-antitrypsin deficiency: Ranges from good to poor; dependent on mutation type, whether liver is involved, and progression of disease

•Liver disease or cirrhosis: Poor, especially if associated with portal hypertension and worse if associated with hepatopulmonary syndrome

•Pancreatitis

When to Refer

•Aspiration

—Pulmonary: If the patient has a pneumonia or pneumonitis episode, stridor, or BRUE (formerly known as apparent life-threatening events)

—GI: Immediately, especially if an alternative method of feeding is required

•GER

—Pulmonary: If the patient has recurrent wheezing and/or coughing episodes, BRUE, or recurrent pneumonia

—GI: If the disease is severe or refractive to medical therapy

•IBD

—Pulmonary: Typically not necessary after a diagnosis of IBD is established because management of IBD alleviates pulmonary involvement; only needed if IBD is refractory to treatment and there is progression of pulmonary disease

—GI: Immediately

—Pulmonary: Not routinely necessary because lung involvement starts in adulthood, but plausible if the family requires education

—GI: Immediately for evaluation and surveillance of liver involvement — A pulmonary or GI specialist may start augmentation therapy

• Liver disease or cirrhosis

—Pulmonary: Dependent on the degree of pulmonary involvement

—Cardiology: If evaluation and management of pulmonary hypertension are required

—GI: Immediate for evaluation and management

•Pancreatitis

—Pulmonary: Not typical unless cystic fibrosis is diagnosed or is a comorbidity or management of pancreatic complication is required (eg, acute respiratory distress syndrome leads to chronic respiratory failure, bronchofistula, empyema)

—GI: Immediate for evaluation and management

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