Bronchiolitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Bronchiolitis is the most common lower respiratory tract infection in pediatric patients between 1 month and 2 years of age. It is usually caused by the respiratory syncytial virus (RSV) and is characterized by inflammation, edema, and necrosis of the bronchiole’s epithelium. It is classified according to histological features as bronchiolitis obliterans, proliferative bronchiolitis, diffuse panbronchiolitis, or respiratory bronchiolitis. The bronchiolitis severity score is used to classify bronchiolitis into 4 classes. Typical clinical manifestations include rhinitis, cough, wheezing, respiratory rales (crackles), use of respiratory accessory muscles, and/or nasal flaring. In adults, common risk factors in the development of bronchiolitis include exposure to cigarette smoke, living in crowded areas, and being immunocompromised. In infants, the risk factors include age < 6 months, lack of breastfeeding, prematurity, and having congenital heart diseases. The mainstay of treatment of bronchiolitis is supportive therapy.

Bronchiolitis was first reported in 1899 when it was discovered by researchers at the University of Minnesota. The disease was fully described in 1901 by Dr. Lange.

Bronchiolitis should be classified in order to understand how it may occur and the clinical manifestations that may be observed. Bronchiolitis is classified based on the patient’s age and the different histological forms of the disease. According to age, bronchiolitis is classified as either adult or infant. Based on the different histological features, it can be classified as acute infectious bronchiolitis, bronchiolitis obliterans, proliferative bronchiolitis, diffuse panbronchiolitis, or respiratory bronchiolitis. Based on the Bronchiolitis Severity Score (BSS), bronchiolitis is classified into 4 classes.

Bronchiolitis is transmitted by air droplets. It is caused by RSV, which infects the nasopharyngeal mucosa. After the infection, the virus spreads to the lower airway tracts until it reaches the bronchioles, where viral replication takes place. The viral infection induces inflammation, which leads to edema and necrosis of the bronchiolar epithelium. Cough reflex occurs due to exposure of the subepithelial tissue and nerve fibers. Vascular permeability increases, leading to edema and swelling. Histopathologically, bronchiolitis obliterans shows intraluminal polyps, inflammatory infiltration, and macrophages. Constrictive bronchiolitis shows thickening of the airways and interluminal narrowing.

Bronchiolitis usually affects children under the age of 2, with a peak age of 3 – 6 months. Bronchiolitis is a common disease in children and sometimes causes severe illness. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. Other viruses that can cause bronchiolitis include adenovirus, influenza, and parainfluenza. It may be caused by bacterial organisms like Legionella pneumophilia and Mycoplasma pneumonia. Other noninfectious causes include smoking, collagen vascular disease, and being post bone marrow transplant.

Bronchiolitis must be differentiated from other respiratory and cardiac diseases that present with similar clinical manifestations. Based on cough and dyspnea, bronchiolitis should be differentiated from asthma, COPD, pneumonia, congestive heart failure, diffuse idiopathic neuroendocrine cell hyperplasia, tuberculosis, pertussis, foreign body aspiration, pulmonary embolism, and Harman-Rich syndrome.

Bronchiolitis is one of the most common acute respiratory diseases that affects infants and children. Bronchiolitis affects around 3,000 per 100,000 children in the United States. It occurs mostly during fall, winter, and early spring. Bronchiolitis can affect any age group, but mostly affects infants, especially those under 2 years. Bronchiolitis occurs more often in boys than girls and is more common among Native Americans, Alaskans, and Hispanics. Bronchiolitis has a low mortality rate despite the high number of hospitalizations associated with the illness.

Bronchiolitis has a different range of risk factors that can be differentiated based on the age. In adults, common risk factors in the development of bronchiolitis include exposure to cigarette smoke, living in crowded areas, and being immunocompromised. In infants, the risk factors include age < 6 months, lack of breastfeeding, prematurity, and having congenital heart diseases.

If left untreated, in the first 2-3 days, a patient with bronchiolitis presents with mild upper respiratory symptoms, shortness of breath, wheezing, persistent prominent cough, and tachypnea. Chest wall retraction and nasal flaring usually develop between the third and seventh day. Symptoms gradually disappear within the next 2 weeks. Complications are usually observed among patients younger than 2 months of age, premature infants, and patients with other medical conditions (congenital heart disease, chronic pulmonary disease, and immunodeficiencies). Severity scores can be used to estimate the prognosis.

Common symptoms of bronchiolitis include fever, cough, dyspnea, and Nasal discharge. Other symptoms include post tussive vomiting and dehydration.

Patients infected with bronchiolitis have a toxic appearance and may be cyanotic. Fever is one of the signs of the disease, but a lack of it does not exclude the diagnosis. Lung examination shows abnormalities in inspection and auscultation. On inspection, intercostal and substernal retractions can be observed. On auscultation, wheezing and crackles can be clearly heard with a decrease in respiratory sounds. Extrapulmonary manifestations can occur as well, including pharyngitis, conjunctivitis, arrhythmias, tachycardia, and seizures.

Bronchiolitis diagnosis depends mainly on the symptoms and physical examination, as the laboratory diagnosis is not specific for the disease. Commonly used lab tests include viral pathogen tests like ELISA, immunofluorescent assays, and optical immunoassays. Complete blood count is also not specific for bronchiolitis. Pulmonary function tests may be helpful in supporting the diagnosis and excluding other obstructive lung diseases.

Chest X-ray in cases of bronchiolitis is usually nonspecific and may be inefficient for differentiating bronchiolitis from other lower respiratory tract infections. A chest X-ray may show atelectasis and consolidations. It is also used in excluding other medical conditions like pneumonia.

CT scan shows nonspecific findings that can be found in other diseases. These findings are centrilobular nodules, bronchiolar wall thickening, ground glass appearance, and parenchymal cysts.

There are no MRI findings associated with bronchiolitis.

There are no additional imaging findings for bronchiolitis.

There are no additional diagnostic findings for bronchiolitis.

The predominant therapy for bronchiolitis is providing supportive measures. Supportive therapy includes frequent, small feeding and oxygen therapy. In severe cases, infants may require intravenous fluids and food via a nasogastric tube. In extreme cases, mechanical ventilation or the use of continuous positive airway pressure (CPAP) might be necessary. Prophylaxis is indicated in infants with hemodynamically significant heart disease and preterm infants who require >21% oxygen for at least the first 28 days of life. The drug of choice for prophylaxis is palivizumab.

Surgical intervention is not recommended for the management of bronchiolitis.

Effective measures for the primary prevention of bronchiolitis include washing hands, avoiding contact with patients with symptomatic respiratory infections, and prevention of tobacco smoke exposure. These preventive measures are to prevent viral dissemination during the RSV season. In patients with a high risk of developing severe infection, passive immunization with palivizumab is recommended.

There are no secondary preventive measures available for bronchiolitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Bronchiolitis was first reported in 1899 when it was discovered by researchers at the University of Minnesota. Bronchiolitis was fully described in 1901 by Dr. Lange.^[1]

• In 1899, bronchiolitis obliterans was first reported among 43,000 autopsies performed by researchers at the University of Minnesota.
• In 1901, Dr. Lange was the first to describe bronchiolitis and endorsed it as a pathological entity.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Bronchiolitis should be classified in order to understand how it may occur and the clinical manifestations that may be observed. Bronchiolitis is classified based on the patient’s age and the different histological forms of the disease. According to age, bronchiolitis is classified as either adult or infant. Based on the different histological features, it can be classified as acute infectious bronchiolitis, bronchiolitis obliterans, proliferative bronchiolitis, diffuse panbronchiolitis, or respiratory bronchiolitis. Based on the Bronchiolitis Severity Score (BSS), bronchiolitis is classified into 4 classes.

Bronchiolitis may be classified in the following ways:

Based on age, brochiolitis may be classified as:

• Adult bronchiolitis
• Infantile bronchiolitis

Based on histological form, bronchiolitis may be classified as: ^[1][2]

Based on Bronchiolitis Severity Score (BSS), bronchiolitis may be classified into 4 classes as follows:^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2], Ahmed Elsaiey, MBBCH [3]

Bronchiolitis is transmitted via air droplets. It is caused by respiratory syncytial virus (RSV), which infects the nasopharyngeal mucosa. After the infection, the virus spreads to the lower airway tracts until it reaches the bronchioles, where viral replication takes place. The viral infection induces inflammation, which leads to edema and necrosis of the bronchiolar epithelium. Cough reflex occurs due to exposure of the subepithelial tissue and nerve fibers. Vascular permeability increases, leading to edema and swelling. Histopathologically, bronchiolitis obliterans shows intraluminal polyps, inflammatory infiltration, and macrophages. Constrictive bronchiolitis shows thickening of the airways and interluminal narrowing.

• Bronchiolitis is not transmissible between individuals. However, when bronchiolitis is caused by respiratory syncytial virus (RSV), it may be transmitted via air droplets.
• Air droplets containing respiratory syncytial virus (RSV) lead to infection of the nasopharyngeal mucosa and subsequent bronchiolitis.

Bronchiolitis is caused by viral replication and inflammation as follows:^[1]

• Starting from the nasopharyngeal mucosa, respiratory syncytial virus (RSV) spreads to the lower respiratory tracts. After reaching the bronchioles, viral replication takes place.
• The respiratory syncytial virus (RSV) infection induces an inflammatory response. This leads to infiltration of inflammatory cells (RSV-specific lymphocytes), edema, and necrosis of the epithelium in the bronchioles. The epithelium is then sloughed into the lumina, causing proliferation of cuboidal epithelial cells without cilia.^[2]
• Respiratory syncytial virus (RSV) causes lysis of the epithelial tissue, which leads to the exposure of the subepithelial tissue and nerve fibers, inducing a cough reflex.
• The vascular permeability increases, which results in edema and swelling.
• This inflammatory process leads to complete or partial obstruction due to reduction in bronchiolar lumina. Accumulation of necrotic tissue produces a valve mechanism, leading to hyperinflation of the lungs.
• By this mechanism, air flow may increase into the lungs by increased negative pressure during inspiration but is unable to flow out of the lung, as the airway’s diameter is smaller during expiration.^[2] Obstructed areas may evolve into areas of atelectasis.
• In children, Kohn channels are not well developed, so atelectasis and hyperinflation may be more severe.

• There are no associated conditions with bronchiolitis.

• There are no specific findings in the gross pathology of bronchiolitis.

Bronchiolitis shows histopathological findings which vary according to different types of bronchiolitis.^[3]

• Bronchiolitis obliterans:
  • Intraluminal polyps (protrusions inside the bronchioles with fibroblastic proliferation)
  • Inflammatory infiltration
  • Type two pneumocytes lining the alveoli
  • Macrophages

• Constrictive bronchiolitis:
  • Scars leading to interluminal narrowing and obstruction
  • Thickening of the airways due to submucosal collagen and fibrosis

• Proliferative bronchiolitis:
  • Histopathology shows Masson bodies (fibrotic buds extending into alveoli)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2]

Bronchiolitis usually affects children under the age of 2 years, with a peak age of 3 – 6 months. Bronchiolitis is a common disease in children and sometimes causes severe illness. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. Other viruses that may cause bronchiolitis include adenovirus, influenza virus and parainfluenza virus. It may be caused by bacterial organisms like Legionella pneumophilia and Mycoplasma pneumonia. Other noninfectious causes include smoking, collagen vascular disease. It may also be caused after bone marrow transplant.

The following viruses may lead to the development of bronchiolitis:^[1]

• Adenovirus
• Influenza
• Parainfluenza
• Respiratory syncytial virus
• Rhinovirus

The following bacterial organisms may lead to the development of bronchiolitis:^[2]

• Legionella pneumophila
• Mycoplasma pneumonia

The most common noninfectious causes of bronchiolitis include the following:^[3]

• Smoking
• Collagen vascular diseases
• Post lung transplant
• Post bone marrow transplant

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Bronchiolitis must be differentiated from other respiratory and cardiac diseases that present with similar clinical manifestations of cough and dyspnea. Bronchiolitis should be differentiated from asthma, COPD, pneumonia, congestive heart failure, diffuse idiopathic neuroendocrine cell hyperplasia, tuberculosis, pertussis, foreign body aspiration, pulmonary embolism, and Harman-Rich syndrome.

Bronchiolitis must be differentiated from other respiratory and cardiac diseases that can cause the similar clinical manifestations like cough and dyspnea. The differentials include the follwoing:^{[1][2][3][4][5]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Bronchiolitis is one of the most common acute respiratory diseases that affects infants and children. The annual incidence of bronchiolitis is 3,000 per 100,000 children in the United States. It occurs mostly during fall, winter, and early spring. Bronchiolitis may affect any age group, but mostly affects infants, especially those under 2 years of age. Bronchiolitis occurs more often in males than females and is more common among Native Americans, Alaskans, and Hispanics. Bronchiolitis has a low mortality rate despite the high number of hospitalizations associated with the illness.

• In the United States, the incidence of bronchiolitis is 3,000 per 100,000 children less than 1 year old.^[1]
• Bronchiolitis has a seasonal pattern that varies according to climate changes in different geographic locations:
  • In temperate climates, RSV infections generally occur during fall, winter, and early spring (between November and March in the northern hemisphere).
  • The timing and severity of RSV circulation in a given community can vary from year to year.
  • In tropical areas, bronchiolitis can be seen throughout the year.
  • Seasonal trends of bronchiolitis could be associated with other etiological pathogens with seasonal patterns.^[2]

• Bronchiolitis may occur in people of any age but it usually affects children between the ages of 1 month and 1 year, with higher rates of severe disease in patients under 6 months of age.
• Almost all children will have had an RSV infection by their second birthday. About 25% to 40% of children exposed to RSV for the first time will develop signs or symptoms of bronchiolitis or pneumonia.^[3]

• Bronchiolitis and severe bronchiolitis is more common in males than in females.^[4]
• The male to female ratio for severe bronchiolitis is 1.5:1.

• Bronchiolitis has been reported to be more prevalent in the Native American, native Alaskan and Hispanic populations. Low socioeconomic status also increases the percentage of the disease among these populations.
• Native American and native Alaskan children tend to have higher hospitalization rates due to bronchiolitis.
  • Native American child hospitalization rate due to bronchiolitis: 70.9 per 1,000 patients.^[4]
  • Native Alaskan child hospitalization rate due to bronchiolitis: 48.2 per 1,000 patients.^[4]

• It has been shown that the rate of hospitalization due to acute respiratory disease, including bronchiolitis, is higher in African American indviduals than in Caucasian individuals.^[5]

• Mortality rate is low despite the high number of hospitalizations:^[4]
  • Mortality rate due to bronchiolitis in the U.S. is 2 deaths per 100,000 live births and less than 400 deaths during a year.
  • Mortality rate due to bronchiolitis in the UK is 1.82 per 100,000 live births.
  • Worldwide, the mortality rate due to acute respiratory infections including bronchiolitis is about 2 million deaths.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Bronchiolitis has a different range of risk factors that can be differentiated based on the age. In adults, common risk factors in the development of bronchiolitis include exposure to cigarette smoke, living in crowded areas, and being immunocompromised. In infants, the risk factors include age < 6 months, lack of breastfeeding, prematurity and having a history of or suffering from congenital heart diseases.

The following characteristics of infants and children may put them at a higher risk of infectious bronchiolitis:^[1][2][3]

• Prematurity, as the maternal transfer of immunoglobulins occurs during the last trimester
• Young children affected with congenital heart diseases are at high risk, due to decreased cardiac output.^[4] These diseases include:
  • Pulmonary hypertension
  • Congestive heart failure
• Lack of breast-feeding
• Children and infants infected by chronic lung disease
• Immunocompromised children

• Exposure to cigarette smoke
• Living in crowded conditions
• Being immunocompromised
• Old age, especially with an underlying heart or lung disease.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

There is insufficient evidence to recommend routine screening for bronchiolitis.

There is insufficient evidence to recommend routine screening for bronchiolitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

If left untreated, bronchiolitis may progress to develop mild upper respiratory symptoms including, cough, rhinorrhea and low grade fever during the first 1-2 days. During third to seventh days of infection, patients develop shortness of breath, wheezing, persistent prominent cough, tachypnea, chest wall retraction, and nasal flaring. Symptoms gradually disappear within the next 2 weeks. Complications are usually observed in patients younger than 2 months of age, premature infants, and patients with other medical conditions (including congenital heart disease, chronic pulmonary disease, and immunodeficiencies). Severity scores can be used to estimate the prognosis.

• Patients usually develop symptoms after one week of initial contact with a symptomatic patient.
• In the first 2-3 days, patients with bronchiolitis present with mild upper respiratory symptoms (cough, rhinorrhea, and low grade fever).
• The acute phase (shortness of breath, wheezing, persistent prominent cough, tachypnea, chest wall retraction, and nasal flaring) usually develops between the third and seventh days.
  • Symptoms gradually disappear within the next 2 weeks (the cough may take longer to resolve).
• Bronchiolitis is usually a self-limited infection that should be eliminated in two weeks after infection in immunocompetent patients. However, dissemination of the virus in immunocompromised patients could remain for several months after initial infection.^[1]

Complications are usually observed in patients younger than 2 months, premature infants and patients with various comorbidities (congenital heart disease, chronic pulmonary disease, and immunodeficiencies). Common complications of bronchiolitis include the following:

• Apnea:^[1]
  • Apnea may appear as the presenting manifestation; however, it may be the consequence of previous mild respiratory infection.
  • More common in children under 2 months of age and premature infants.
  • Observed in 3% to 25% of patients.
• Aspiration pneumonia
• Recurrent wheezing episodes:
  • Observed in 30%-50% of hospitalized patients with bronchiolitis.
  • Episodes usually disappear before adolescence.
• Associated bacterial infections:
  • The most common bacterial infections complicating bronchiolitis are urinary tract infections (UTI) and acute otitis media (AOM).
  • Bacterial co-infections may appear in up to 7 % of patients with bronchiolitis.

The prognosis of bronchiolitis is generally good, as most children show gradual symptomatic improvement within 2 weeks of symptom onset. Albeit the good prognosis, the rate of hospitalization is high (71 per 1000 infants for 2003) and has increased during the last two decades. The mortality rate of bronchiolitis is very low (2 deaths per 100,000 live births in the U.S. and 1.82 per 100,000 live births in the UK).^[2]

Clinical scoring systems such as the following may help predict the prognosis:

• Bronchiolitis severity score (BSS)^[3]
• Court’s scale^[4]
• Respiratory distress assessment instrument (RDAI)^[5]
• Respiratory distress observation scale (RDOS)^[6]
• Tal and modified-Tal scoring systems^[7]

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