Respiratory Disorders Associated With Gastrointestinal and Hepatic Disease

Chapter 92


Respiratory Disorders Associated With Gastrointestinal and Hepatic Disease

Edward W. Fong, MD


Many different respiratory disease processes are associated with gastrointestinal (GI) and liver disease (Tables 92-1 and 92-2, Box 92-1).

Respiratory disease is typically a complication or sequela of GI or hepatic disease. It may be variable in course and prognosis:

It may be transient and mild if GI or hepatic disease is self-limiting and/or amenable to a treatment regimen, such as gastroesophageal reflux (GER).

It may be debilitating and severe if GI or hepatic disease is chronic, as in the case of progressive disease with limited response to treatment regimen, such as α1-antitrypsin deficiency with liver disease, severe sarcoidosis, or Langerhans cell histiocytosis.

Table 92-1. Pulmonary Disorders Associated with GI Disorders
Gastrointestinal Disease Pulmonary Disorder
Gastroesophageal reflux disease Recurrent or persistent cough and/or wheeze, apnea, nocturnal cough, recurrent pneumonia, hemoptysis, stridor, hypertrophied adenoids, snoring
Aspiration Recurrent or chronic infection, hyperreactive airway disease, airway inflammation, apnea, bronchiectasis, recurrent or chronic cough and/or wheeze, vocal hoarseness
Inflammatory bowel disease Airway inflammation, bronchiolitis obliterans, interstitial lung disease, granulomas
Cystic fibrosis Tracheobronchitis, pneumonia, atelectasis, bronchiectasis, hyperreactive airway disease, cysts, bullae, pneumothorax, pulmonary hemorrhage, pulmonary hypertension

Table 92-2. Pulmonary Disorders Associated with Hepatic Disorders
Hepatic Disease Pulmonary Disorder
Infections Hilar adenopathy, pneumonia tracheobronchitis, pleural effusions
α1-antitrypsin deficiency Wheezing, chronic obstructive pulmonary disease, emphysema, recurrent lung infections in adults
Wilson disease Hepatopulmonary syndrome, clubbing, cyanosis
Primary sclerosing cholangitis Bronchitis, bronchiectasis
Chronic granulomatous disease of childhood Hilar adenopathy, pneumonia, atelectasis, pleural effusion, abscess, honeycomb lung, pulmonary hypertension
Cystic fibrosis Tracheobronchitis, pneumonia, atelectasis, bronchiectasis, hyperreactive airway disease, cysts, bullae, pneumothorax, pulmonary hemorrhage, pulmonary hypertension
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Pulmonary angiodysplasia
Langerhans cell histiocytosis Hilar adenopathy, pneumonitis, interstitial fibrosis, pleural effusion, pneumothorax, honeycomb lung, pulmonary hypertension
Sarcoidosis Hilar adenopathy, reticulonodular infiltrates, atelectasis, hyperreactive airway disease, granulomata, bronchial stenosis, interstitial pneumonitis, interstitial fibrosis, pleural effusion, pneumothorax, nodules, cysts, pulmonary hemorrhage, pulmonary hypertension
Chronic active hepatitis Pneumonia, atelectasis, interstitial pneumonitis, interstitial fibrosis, fibrosing alveolitis, pleural effusion, pulmonary hypertension, pulmonary hemorrhage
Liver transplant Pleural effusion, pneumonia, atelectasis, pulmonary edema, acute respiratory distress syndrome
Cirrhosis (alcoholic, post-necrotic, cryptogenic) Pneumonia, pleural effusion, pulmonary angiodysplasia, pleural vasodilatations, pulmonary hypertension
Primary biliary cirrhosis Hyperreactive airway disease, interstitial pneumonitis, interstitial fibrosis, fibrosing alveolitis, pulmonary hypertension
Portal hypertension Dyspnea, pulmonary hypertension, hepatopulmonary syndrome, hemoptysis

Adapted from Ozdogan S, Fong E. Pulmonary complications of gastrointestinal diseases. In: Light MJ, Blaisdell CJ, Homnick DN, Schechter MS, Weinberger MM, eds. Pediatric Pulmonology. Elk Grove Village, IL: American Academy of Pediatrics;2011:799–814.

Box 92-1. Pulmonary Disorders Associated with Pancreatitis

Acute Pancreatitis Chronic Pancreatitis
Pleural effusion Pancreaticopleural fistula
Empyema Pancreaticobronchial fistula
Hemidiaphragm elevation Pancreaticobronchopleural fistula
Atelectasis: left lower lobe Recurrent pleural effusion
Pneumonia: left lower lobe Recurrent lobar pneumonia
Pulmonary embolism  
Pulmonary infarction  
Acute respiratory distress syndrome  
Pulmonary edema  

Adapted from Ozdogan S, Fong E. Pulmonary complications of gastrointestinal diseases. In: Light MJ, Blaisdell CJ, Homnick DN, Schechter MS, Weinberger MM, eds. Pediatric Pulmonology. Elk Grove Village, IL: American Academy of Pediatrics;2011:799–814.

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.


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.

Inflammatory bowel disease (IBD): The mechanism is not understood; direct inflammation of the airways and parenchyma caused by underlying inflammatory process is the most likely.

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

Diagnostic Considerations


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

The lipid-laden macrophage index from bronchoalveolar lavage (BAL) may be helpful, but results need to interpreted in context, because this index is increased in a number of other inflammatory airway conditions (Figure 92-1).


Clinical evaluation

Esophageal pH level and impedance monitoring

Imaging studies: Upper GI study is limited in both sensitivity and specificity but is frequently used.

Gastric-emptying scintigraphy may be used if delayed emptying is the suspected cause of symptoms.

Endoscopy with or without biopsy

Lipid-laden macrophage index from BAL (also see Figure 92-1)


Figure 92-1. Photomicrograph (red oil O stain; original magnification, ×1,000) shows a lipid-laden macrophage. Image used with the permission of Elaine Cham, MD, Department of pathology, UCSF Benioff Children’s Hospital, Oakland.


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


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



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


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

Surgical: Nissen fundoplication


Dependent on type; immunosuppression, chemotherapy

α1-antitrypsin deficiency

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


~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


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


When to Refer


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


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


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

α1-antitrypsin deficiency

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


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

Resources for Families

Crohn’s and Colitis Foundation of America.

IBD Support Foundation.

Alpha-1 Foundation.

Only gold members can continue reading. Log In or Register to continue

Aug 8, 2019 | Posted by in PEDIATRICS | Comments Off on Respiratory Disorders Associated With Gastrointestinal and Hepatic Disease
Premium Wordpress Themes by UFO Themes