Acute Bronchiolitis and Inflammation of the Airway

Infection can cause obstruction to flow by internal narrowing of the airways.

Acute bronchiolitis is predominantly a viral disease. RSV is responsible for >50% of cases(Chapter 252). Other agents include parainfluenza (Chapter 251), adenovirus, and Mycoplasma. Emerging pathogens include human metapneumovirus (Chapter 253) and human bocavirus, which may be a primary cause of viral respiratory infection or occur as a co-infection with RSV. There is no evidence of a bacterial cause for bronchiolitis, although bacterial pneumonia is sometimes confused clinically with bronchiolitis, but bronchiolitis is rarely followed by bacterial superinfection. Concurrent infection with viral bronchiolitis and pertussis has been described.

Approximately 75,000-125,000 children <1 yr old are hospitalized annually in the United States due to RSV infection. Increasing rates of hospitalization might reflect increased attendance of infants in daycare centers, changes in criteria for hospital admission, and/or improved survival of premature infants and others at risk for severe RSV-associated disease.

Bronchiolitis is more common in boys, in those who have not been breast-fed, and in those who live in crowded conditions. Risk is higher for infants with young mothers or mothers who smoked during pregnancy. Older family members are a common source of infection; they might only experience minor upper respiratory symptoms (colds). The clinical manifestations of lower respiratory tract illness (LRTI) seen in young infants may be minimal in older patients, in whom bronchiolar edema is better tolerated.

Not all infected infants develop LRTI. Host anatomic and immunologic factors play a significant role in the severity of the clinical syndrome, as does the nature of the viral pathogen. Infants with pre-existent smaller airways and diminished lung function have a more-severe course. In addition, RSV infection incites a complex immune response. Eosinophils degranulate and release eosinophil cationic protein, which is cytotoxic to airway epithelium. Innate immunity plays a significant role and can depend on polymorphisms in toll-like receptor (TLR), interferon (IF), interleukins (IL), and nuclear factor κB (NFκB). Chemokines and cytokines such as tumor necrosis factor α (TNF-α) may be differentially expressed depending on the inciting virus. Co-infection with >1 virus can also alter the clinical manifestations and/or severity of presentation.

Acute bronchiolitis is characterized by bronchiolar obstruction with edema, mucus, and cellular debris. Even minor bronchiolar wall thickening significantly affects airflow because resistance is inversely proportional to the 4th power of the radius of the bronchiolar passage. Resistance in the small air passages is increased during both inspiration and exhalation, but because the radius of an airway is smaller during expiration, the resultant respiratory obstruction leads to early air trapping and overinflation. If obstruction becomes complete, trapped distal air will be resorbed and the child will develop atelectasis.

Hypoxemia is a consequence of ventilation-perfusion mismatch early in the course. With severe obstructive disease and tiring of respiratory effort, hypercapnia can develop.

Chronic infectious causes of wheezing should be considered in infants who seem to fall out of the range of a normal clinical course. Cystic fibrosis is one such entity; suspicion increases in a patient with persistent respiratory symptoms, digital clubbing, malabsorption, failure to thrive, electrolyte abnormalities, or a resistance to bronchodilator treatment(Chapter 395).

Allergy and asthma are important causes of wheezing and probably generate the most questions by the parents of a wheezing infant. Asthma is characterized by airway inflammation, bronchial hyperreactivity, and reversibility of obstruction(Chapter 138). Three identified patterns of infant wheezing are the transient early wheezer, the persistent wheezer, and the late-onset wheezer. Transient early wheezers constituted 19.9% of the general population, and they had wheezing at least once with a lower respiratory infection before the age of 3 yr but never wheezed again. The persistent wheezer constituted 13.7% of the general population, had wheezing episodes before age 3 yr, and were still wheezing at 6 yr of age. The late-onset wheezer constituted 15% of the general population, had no wheezing by 3 yr, but was wheezing by 6 yr. The other of the children had never wheezed by 6 yr. Of all the infants who wheezed before 3 yr old, almost 60% stopped wheezing by 6 yr.

Multiple studies have tried to predict which early wheezers will go on to have asthma in later life. Risk factors for persistent wheezing include parental history of asthma and allergies, maternal smoking, persistent rhinitis (apart from acute upper respiratory tract infections), eczema at <1 yr of age, and frequent episodes of wheezing during infancy.

Other Causes

Congenital malformations of the respiratory tract cause wheezing in early infancy. These findings can be diffuse or focal and can be from an external compression or an intrinsic abnormality. External vascular compression includes a vascular ring, in which the trachea and esophagus are surrounded completely by vascular structures, or a vascular sling, in which the trachea and esophagus are not completely encircled(Chapter 426). Cardiovascular causes of wheezing include dilated chambers of the heart including massive cardiomegaly, left atrial enlargement, and dilated pulmonary arteries. Pulmonary edema caused by heart failure can also cause wheezing by lymphatic and bronchial vessel engorgement that leads to obstruction and edema of the bronchioles and further obstruction (Chapter 436).

Foreign body aspiration (Chapter 379) can cause acute or chronic wheezing. It is estimated that 78% of those who die from foreign body aspiration are between 2 mo and 4 yr old. Even in young infants, a foreign body can be ingested if given to the infant by another person such as an older sibling. Infants who have atypical histories or misleading clinical and radiologic findings can receive a misdiagnosis of asthma or another obstructive disorder as inflammation and granulation develop around the foreign body. Esophageal foreign body can transmit pressure to the membranous trachea, causing compromise of the airway lumen.

Gastroesophageal reflux (Chapter 315.1) can cause wheezing with or without direct aspiration into the tracheobronchial tree. Without aspiration, the reflux is thought to trigger a vagal or neural reflex, causing increased airway resistance and airway reactivity. Aspiration from gastroesophageal reflux or from the direct aspiration from oral liquids can also cause wheezing.

Trauma and tumors are much rarer causes of wheezing in infants. Trauma of any type to the tracheobronchial tree can cause an obstruction to airflow. Accidental or nonaccidental aspirations, burns, or scalds of the tracheobronchial tree can cause inflammation of the airways and subsequent wheezing. Any space-occupying lesion either in the lung itself or extrinsic to the lung can cause tracheobronchial compression and obstruction to airflow.

History and Physical Examination

Initial history of a wheezing infant should include accounts of the recent event including onset, duration, and associated factors (Table 383-2). Birth history includes weeks of gestation, neonatal intensive care unit admission, history of intubation or oxygen requirement, maternal complications including infection with herpes simplex virus (HSV) or HIV, and prenatal smoke exposure. Past medical history includes any comorbid conditions including syndromes or associations. Family history of cystic fibrosis, immunodeficiencies, asthma in a 1st-degree relative, or any other recurrent respiratory conditions in children should be obtained. Social history should include an environmental history including any smokers at home, inside or out, daycare exposure, number of siblings, occupation of inhabitants of the home, pets, tuberculosis exposure, and concerns regarding home environment (e.g., dust mites, construction dust, heating and cooling techniques, mold, cockroaches).

On physical examination, evaluation of the patient’s vital signs with special attention to the respiratory rate and the pulse oximetry reading for oxygen saturation is an important initial step. There should also be a thorough review of the patient’s growth chart for signs of failure to thrive. Wheezing produces an expiratory whistling sound that can be polyphonic or monophonic. Expiratory time may be prolonged. Biphasic wheezing can occur if there is a central, large airway obstruction. The lack of audible wheezing is not reassuring if the infant shows other signs of respiratory distress because complete obstruction to airflow can eliminate the turbulence that causes the sound to resonate. Aeration should be noted and a trial of a bronchodilator may be warranted to evaluate for any change in wheezing after treatment. Listening to breath sounds over the neck helps differentiate upper airway from lower airway sounds. The absence or presence of stridor should be noted and appreciated on inspiration. Signs of respiratory distress include tachypnea, increased respiratory effort, nasal flaring, tracheal tugging, subcostal and intercostal retractions, and excessive use of accessory muscles. In the upper airway, signs of atopy, including boggy turbinates and posterior oropharynx cobblestoning, can be evaluated in older infants. It is also useful to evaluate the skin of the patient for eczema and any significant hemangiomas; midline lesions may be associated with an intrathoracic lesion. Digital clubbing should be noted(Chapter 366).

Acute bronchiolitis is usually preceded by exposure to an older contact with a minor respiratory syndrome within the previous week. The infant 1st develops a mild upper respiratory tract infection with sneezing and clear rhinorrhea. This may be accompanied by diminished appetite and fever of 38.5-39°C (101-102°F), although the temperature can range from subnormal to markedly elevated. Gradually, respiratory distress ensues, with paroxysmal wheezy cough, dyspnea, and irritability. The infant is often tachypneic, which can interfere with feeding. The child does not usually have other systemic complaints, such as diarrhea or vomiting. Apnea may be more prominent than wheezing early in the course of the disease, particularly with very young infants (<2 mo old) or former premature infants.

The physical examination is often dominated by wheezing. The degree of tachypnea does not always correlate with the degree of hypoxemia or hypercarbia, so pulse oximetry and noninvasive determination of carbon dioxide is essential. Work of breathing may be markedly increased, with nasal flaring and retractions. Auscultation might reveal fine crackles or overt wheezes, with prolongation of the expiratory phase of breathing. Barely audible breath sounds suggest very severe disease with nearly complete bronchiolar obstruction. Hyperinflation of the lungs can permit palpation of the liver and spleen.

Diagnostic Evaluation

Initial evaluation depends on likely etiology; a baseline chest radiograph, including posteroanterior and lateral films, is warranted in many cases and for any infant in acute respiratory distress. Infiltrates are most often found in wheezing infants who have a pulse oximetry reading <93%, grunting, decreased breath sounds, prolonged inspiratory to expiratory ratio, and crackles. The chest radiograph may also be useful for evaluating hyperinflation (common in bronchiolitis and viral pneumonia), signs of chronic disease such as bronchiectasis, or a space-occupying lesion causing airway compression. A trial of bronchodilator may be diagnostic as well as therapeutic because these medications can reverse conditions such as bronchiolitis (occasionally) and asthma but will not affect a fixed obstruction. Bronchodilators potentially can worsen a case of wheezing caused by tracheal or bronchial malacia. A sweat test to evaluate for cystic fibrosis and evaluation of baseline immune status are reasonable in infants with recurrent wheezing or complicated courses. Further evaluation such as upper gastrointestinal (GI) contrast x-rays, chest CT, bronchoscopy, infant pulmonary function testing, video swallow study, and pH probe can be considered second-tier diagnostic procedures in complicated patients.

The diagnosis of acute bronchiolitis is clinical, particularly in a previously healthy infant presenting with a first-time wheezing episode during a community outbreak. Chest radiography can reveal hyperinflated lungs with patchy atelectasis. The white blood cell and differential counts are usually normal. Viral testing (polymerase chain reaction, rapid immunofluorescence, or viral culture) is helpful if the diagnosis is uncertain or for epidemiologic purposes. Because concurrent bacterial infection (sepsis, pneumonia, meningitis) is highly unlikely, confirmation of viral bronchiolitis can obviate the need for a sepsis evaluation in a febrile infant and assist with respiratory precautions and isolation if the patient requires hospitalization.

Clinical Manifestations

Acute bronchitis often follows a viral upper respiratory tract infection. It is more common in the winter when respiratory viral syndromes predominate. The tracheobronchial epithelium is invaded by the infectious agent, leading to activation of inflammatory cells and release of cytokines. Constitutional symptoms including fever and malaise follow. The tracheobronchial epithelium can become significantly damaged or hypersensitized, leading to a protracted cough lasting 1-3 wk.

The child 1st presents with nonspecific upper respiratory infectious symptoms, such as rhinitis. Three to 4 days later, a frequent, dry, hacking cough develops, which may or may not be productive. After several days, the sputum can become purulent, indicating leukocyte migration but not necessarily bacterial infection. Many children swallow their sputum, and this can produce emesis. Chest pain may be a prominent complaint in older children and is exacerbated by coughing. The mucus gradually thins, usually within 5-10 days, and then the cough gradually abates. The entire episode usually lasts about 2 wk and seldom >3 wk.

Findings on physical examination vary with the age of the patient and stage of the disease. Early findings are absent or are low-grade fever and upper respiratory signs such as nasopharyngitis, conjunctivitis, and rhinitis. Auscultation of the chest may be unremarkable at this early phase. As the syndrome progresses and cough worsens, breath sounds become coarse, with coarse and fine crackles and scattered high-pitched wheezing. Chest radiographs are normal or can have increased bronchial markings.

The principal objective of the clinician is to exclude pneumonia, which is more likely caused by bacterial agents requiring antibiotic therapy. In adults, absence of abnormality of vital signs (tachycardia, tachypnea, fever) and a normal physical examination of the chest reduce the likelihood of pneumonia.

Differential Diagnosis

Persistent or recurrent symptoms should lead the clinician to consider entities other than acute bronchitis. Many entities manifest with cough as a prominent symptom (Table 383-3).

Table 383-3 DISORDERS WITH COUGH AS A PROMINENT FINDING

Treatment

There is no specific therapy for acute bronchitis. The disease is self-limited, and antibiotics, although often prescribed, do not hasten improvement. Frequent shifts in position can facilitate pulmonary drainage in infants. Older children are sometimes more comfortable with humidity, but this does not shorten the disease course. Cough suppressants can relieve symptoms but can also increase the risk of suppuration and inspissated secretions and, therefore, should be used judiciously. Antihistamines dry secretions and are not helpful; expectorants are likewise not indicated.