Wheezing in the Pediatric Patient

This CE activity is approved by EMS World Magazine, an organization accredited by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS) for 1 CEU. To take the CE test that accompanies this article, go to www.rapidce.com to take the test and immediately receive your CE credit. Questions? E-mail editor@EMSWorld.com.?

Objectives

• Describe the pathophysiology of bronchiolitis and list signs and symptoms
• Describe the treatment of a patient with bronchiolitis
• Describe the pathophysiology of asthma and list signs and symptoms
• Describe the treatment of a patient with asthma
• Describe the similarities and differences between the pathophysiology of bronchiolitis and asthma
• Discuss the epidemiological characteristics of bronchiolitis and asthma

   A wheeze is a high-pitched, musical, continuous sound that originates from oscillations in narrowed airways. Wheezing is most often the result of bronchiolitis in infants and asthma in older children. This article will discuss the similarities and differences between these two childhood diseases, along with management of the infant or child with wheezing.

Bronchiolitis

Epidemiology

   In children under 1 year of age, the respiratory syncytial virus (RSV) is estimated to be responsible for up to 70% of cases in previously healthy children.¹ RSV is a virus of the family Paramyxoviridae, which includes many common respiratory viruses, such as those that cause measles and mumps. The name RSV derives from the fact that it A) is a virus that causes respiratory tract infections, and B) combines with nearby viruses to form a syncytia, or virus mass. The virus is so ubiquitous that nearly all children will have had an RSV infection by their second birthday. After first-time exposure to RSV, 25%-40% of infants and children will exhibit signs or symptoms of bronchiolitis, and 0.5%-2% will require hospitalization. Most children hospitalized for RSV infection are under 6 months of age.² Bronchiolitis attributable to RSV was the leading cause of hospitalization among the general population of infants in the United States between 1997-2000, accounting for an estimated 96,000 hospitalizations during that time.³

   Mortality associated with bronchiolitis has decreased in past decades, although young infants can still die from bronchiolitis. Those tend to be the sick ones who then develop bronchiolitis.^3,4 The mortality rate is less than 1%, with fewer than 500 deaths a year attributed to RSV in the United States. Increased morbidity and mortality occurs in high-risk patients,^3,5,6 including those younger than 6 weeks old, and those with a history of premature birth, hypoxia, congenital heart disease, chronic lung disease or immune deficiency.^7,8,9 Bronchiolitis is more common in males, infants living in crowded conditions, and infants who have not been breast-fed.^10,11,12

Pathophysiology

   Bronchiolitis is predominantly a viral disease, with no evidence supporting bacterial etiologies. In addition to RSV, other infectious agents include parainfluenza, adenovirus, rhinovirus, mycoplasma and metapneumovirus. Viruses are spread from person to person by direct contact with nasal and oral secretions, airborne droplets produced with sneezing and coughing, and fomites. A fomite is any inanimate object, such as a bedsheet or clothing, capable of carrying and transferring an infectious agent.

   After inoculation, viral replication begins in the epithelial cells of the upper airway, then spreads to the mucosal surfaces of the lower respiratory tract, including the bronchioles. Infection of the epithelial cells results in their destruction via normal cell lysis, courtesy of the immune system, or via apoptosis, genetically preprogrammed cell death. Necrotic cells slough off and release inflammatory mediators, leading to airway inflammation and edema. In addition, mucus production is increased. This combination of cellular debris, edema and increased mucus production results in narrowing and obstruction of the bronchioles, increased resistance to air flow, decreased ventilation and air trapping.

   In addition to infants, there is also a risk of transmission to adults, especially the immunocompromised or elderly. As such, all medical practitioners should employ adequate personal protective equipment to protect themselves and others.

Clinical Exam

   Typically, the patient with bronchiolitis is younger than 12 months and presents during the winter months. The parents of a child with bronchiolitis will describe a 1-5-day history of malaise, fever, irritability or poor feeding. A cough is common, and noisy breathing, grunting, dyspnea and increased work of breathing may be apparent; parents may even describe an audible wheeze. A parent or caregiver may be able to recall exposure to a person with a respiratory infection within the previous week. It's important to determine if the patient has a history of premature birth, hypoxia, congenital heart disease, chronic lung disease or immune deficiency, all of which can complicate the course of disease. A caregiver may also describe periods of apnea, especially in infants younger than 6 weeks. It is important to gather information about the patient's hydration status, including the presence of vomiting and/or diarrhea, urine output as determined by the number of diapers in a 24-hour period, and the amount and frequency of fluid intake and feedings. Infants with tachypnea may have difficulty breast-feeding or taking a bottle.

   Physical exam findings associated with bronchiolitis include fever, wheezing, tachycardia and tachypnea. Signs of increased respiratory distress, including accessory muscle use, nasal flaring, retractions, cyanosis and developing hypoxia, suggest severe disease and airflow obstruction and require aggressive management. Pulse oximetry should be performed on all patients with suspected bronchiolitis. It is inexpensive and provides quick and objective data regarding the degree of hypoxia present in a patient.

   The combination of poor feeding and increased insensible fluid loss secondary to tachypnea can result in dehydration and hypovolemic shock, further complicating the respiratory compromise. As such, a careful assessment of the fontanel, skin turgor and mucous membranes would be appropriate.

Asthma

Epidemiology

   Asthma is one of the few chronic childhood diseases for which there have been increases in prevalence, morbidity and mortality in recent decades. A CDC study showed 34 million people (11.5%), or one in nine Americans, have been diagnosed with asthma during their lifetime. Current asthma prevalence is higher among females (8.9%) than males (6.5%), and is higher among children ages 17 years and younger (9.1%) than adults (7.3%).¹³ In the past 25 years, childhood asthma rates have more than doubled.

   An average annual 1.8 million emergency department visits for asthma were calculated for the three-year period from 2001 until 2003; 1.1 million visits were for adults and 696,900 visits were for children. More visits were made by male children (423,800) than female children (273,100). During the same three-year period, an average annual 4,210 deaths from asthma occurred, with 200 of those deaths occurring in persons less than 18 years of age.¹⁴ There are definite racial disparities among children with this disease. Compared with white children, black children have a 60% higher prevalence rate, a 260% higher ED visit rate, a 250% higher hospitalization rate and a 500% higher death rate due to asthma.¹⁵ In the United States, childhood asthma is the most common cause of childhood emergency department visits, hospitalizations and missed school days (10.1 million school days lost a year).

Pathophysiology

   Asthma is a chronic inflammatory disorder of the airways characterized by variable and recurring symptoms arising from episodic and reversible airflow obstruction. This airflow obstruction is the result of numerous pathological processes, including bronchoconstriction, airway hyperresponsiveness, inflammation and edema, and increased pulmonary secretions. Asthma may be classified as atopic (extrinsic) or non-atopic (intrinsic) based on the causes of symptoms. The term atopy refers to a genetic predisposition towards the development of immediate hypersensitivity reactions to common environmental allergens. Atopic asthma is caused by allergens like pollen or animal dander. Non-atopic asthma, in contrast, is not caused by an exposure to an allergen, but is usually a reaction to a virus or upper respiratory infection.

   An exacerbation of asthma occurs in two phases: early and late. During the early phase, inhalation of an allergen or other irritant results in immediate bronchoconstriction. During the late phase, airway inflammation, edema and hyperresponsiveness further contribute to airflow obstruction. It is worth taking a closer look at these components of asthma.

Bronchoconstriction

   In atopic asthma, allergen-induced bronchoconstriction results from the IgE-dependent release of bronchoconstrictor mediators, such as histamine from mast cells. This occurs when IgE antibodies identify an allergen and attach to them, forming an allergen-antibody complex. This allergen-antibody complex is then recognized by and bound to a mast cell. The mast cell degranulates and releases histamine, resulting in immediate bronchoconstriction. In addition, other stimuli such as exercise, cold air, inhalation of irritants and even stress can result in acute bronchoconstriction. Bronchoconstriction is the most immediate, dominant physiological event early in an asthma attack, and airflow obstruction can be reversed at this time with the administration of bronchodilators.

Airway Inflammation and Edema

   Cells of the immune system that release inflammatory mediators include lymphocytes, mast cells, eosinophils, and neutrophils to a lesser degree. Release of these mediators, such as histamine and cytokines, results in increased capillary permeability and edema. The airflow obstruction caused by airway edema can be worsened by mucus hypersecretion and the formation of mucus plugs. Airway inflammation and edema occur later in an asthma exacerbation than does bronchoconstriction.

Airway Hyperresponsiveness

   The term airway hyperresponsiveness is used to describe the exaggerated bronchoconstrictor response that occurs in asthma and is associated with inflammation. The more inflammation that is present, the greater the hyperresponsiveness. A higher degree of hyperresponsiveness correlates with an increase in the clinical severity of asthma. Treatment that targets inflammation can reduce airway hyperresponsiveness and aid in asthma control.

Clinical Exam

   When evaluating the child with asthma, the prehospital care provider should inquire as to the age of the patient, the duration and severity of the event, recent medication use, and if there is a possibility of a choking episode and foreign body aspiration. If there have been other attacks, the parents should attempt to compare the present ones with past attacks. Identify all medication types and doses. Any history of difficulty sleeping or eating during the attack suggests a moderate to severe exacerbation.

Common clinical exam findings associated with asthma include tachypnea, tachycardia, wheezing and dry cough. In addition to wheezing, crackles or rhonchi may be auscultated over areas where mucus and inflammatory exudate have accumulated in the airways. A silent chest can be an ominous sign in asthma, as it may indicate that ventilation is extremely diminished or nonexistent. Another ominous sign is head-bobbing or lethargy, indicating that the patient is becoming tired, hypoxic, or approaching respiratory failure. An oxygen saturation should be determined, as it can assist in determining the degree of illness.¹⁶ During the early stages of an exacerbation of asthma, hyperventilation results in hypocapnia and a decreased end-tidal carbon dioxide (ETCO2) reading. As bronchoconstriction and edema worsen airflow, alveolar ventilation decreases and hypercapnia develops, resulting in an increase in ETCO2. No single asthma scoring table has been universally adopted to assess the degree of illness or aid in decision-making regarding management, but Table 1 can be used as a guide.

   Measuring peak expiratory flow rate (PEFR) is an easy and objective method of determining the severity of asthma in an adult, but arguably has limited utility in the infant and child with asthma, who may be unable to follow commands necessary for this testing. In one study, just two-thirds of children above age 5 were able to complete PEFR testing during an asthma exacerbation.¹⁷

Management of Wheezing

   After initial evaluation of airway, breathing and circulation, and the immediate treatment of life-threats identified during the primary exam, the treatment of wheezing in the pediatric patient revolves around increasing ventilation and oxygenation through the reversal of bronchoconstriction and airway edema.

Oxygen

   All patients with wheezing should be administered oxygen via an appropriate delivery device to maintain a SpO₂ above 90%. Patients with adequate breathing (rate and tidal volume normal for age) can utilize a nasal cannula or nonrebreather mask, while patients with inadequate breathing (rate and/or tidal volume outside of norms for age) require BVM ventilation. Care must be taken when providing BVM or mechanical ventilation, as air trapping can result in increased intrathoracic pressures and the risk of decreased venous return. This could lead to decreased cardiac output and barotrauma, resulting in pneumothorax. As such, adequate (extended) expiratory time must be allowed for air to exit from the lungs. Permissive hypercapnia is a term used to describe the increase in ETCO₂ that occurs when a strategy of minimizing tidal volumes and respiratory rate in order to minimize peak airway and intrathoracic pressures is utilized.

   Some EMS and critical care transport services use heliox in the treatment of severe asthma. Heliox is a low-density mixture (an 80:20 ratio is common) of helium and oxygen that results in less-turbulent flow through airways narrowed by bronchoconstriction and edema. In theory, the decrease in turbulent airflow should result in decreased work of breathing, less respiratory muscle fatigue, and a lower likelihood of respiratory failure. However, an analysis of clinical trials assessing the use of heliox suggests that there is insufficient evidence to support widespread use, and it is usually considered only for children with severe exacerbation of asthma not responding to conventional therapy.¹⁸

   A relatively new form of oxygen therapy used in cases of mild wheezing in neonates and infants is heated, humidified, high-flow nasal cannula (HFNC) therapy. HFNC allows for the delivery of high gas flows (1-8 L/min in infants), with or without an increased oxygen concentration.¹⁹ HFNC provides some level of continuous positive airway pressure (CPAP), though exact rates are hard to predict. Neonatal studies show that the amount of CPAP generated depends on the flow delivered relative to the size of the patient and on the leak around the nasal cannula.^20,21,22

   Continuous positive airway pressure, or more specifically, nasal continuous positive airway pressure (NCPAP), has been shown to improve clinical scores, decrease respiratory rate and improve ventilation in infants with bronchiolitis or asthma.^23,24 Like PEFP, however, NCPAP is not typically well tolerated by infants and children.²⁵ Infants and children with more significant respiratory distress or with apnea require endotracheal intubation and mechanical ventilation to support oxygenation and ventilation. A hallmark of respiratory failure and impending respiratory arrest is the restless, agitated child in respiratory distress who suddenly becomes compliant. This may indicate that the patient is tired and/or severely hypercapnic.

Beta-2 Agonists

   Short-acting beta-2 agonists (SABAs), such as albuterol and levalbuterol, delivered by small-volume nebulizer, are the treatment of choice for children with acute exacerbation of asthma. The evidence supporting their use in children with wheezing secondary to bronchiolitis is less conclusive; however, there is enough clinical overlap between asthma and bronchiolitis that the two cannot be distinguished on physical examination findings alone. Therefore, for the paramedic working in the prehospital environment, management of the infant or child presenting with wheezing of unknown etiology should include the use of SABAs.

Beta-agonists activate beta-2 receptors in the lungs, resulting in relaxation of bronchial smooth muscle, bronchodilation and improved airflow.

   Epinephrine 1:1000 and terbutaline, administered subcutaneously, can be utilized in moderate to severe exacerbations of asthma. Due to its profound cardiovascular effects, epinephrine is commonly reserved for those infant and child patients in moderate to severe asthma; it is not recommended in those pediatric patients with comorbidities (e.g., congenital heart disease) that may be complicated by the excessive cardiac stimulation that accompanies its use.

Anticholinergics

   Anticholinergics inhibit muscarinic cholinergic receptors in the airway, reducing the intrinsic vagal tone present and resulting in bronchodilation. Ipratropium bromide (IB) is an anticholinergic commonly used in the prehospital environment. The onset of action of IB is long, and clinical benefits can be delayed for up to 60 minutes. Despite the delayed onset of action, studies have shown that the use of SABAs with IB is more effective in reversing bronchoconstriction than using SABAs alone.^26,27 It is not uncommon to have prehospital protocols that allow for administration of both medications, which are placed into a small-volume nebulizer and administered concurrently.

Corticosteroids

   While corticosteroids are commonly used in the treatment of moderate to severe asthma, their use in bronchiolitis is limited. They are not considered a standard of care for the management of bronchiolitis (although they are used), and are not recommended for use in previously healthy infants with RSV.²⁸ Corticosteroids are used to reduce the inflammation and edema associated with both acute exacerbation and chronic asthma, and are most commonly administered via IV in the prehospital environment. Like anticholinergics, there is a delayed onset of action (up to several hours), so the benefits may not be clinically apparent in the prehospital environment, but there is an advantage to early administration. An example of an intravenous corticosteroid commonly utilized by EMS is methylprednisolone (Solu-Medrol).

Magnesium Sulfate

   There is sufficient evidence to suggest that IV or inhaled magnesium sulfate may benefit both adults and children with severe asthma.^29,30 Magnesium acts as a smooth muscle relaxant and promotes bronchodilation, and the administration of magnesium has been shown to result in decreased airway resistance and improved ventilation in adults. Current recommendations published in the National Heart, Lung, and Blood Institute, National Institutes of Health's National Asthma Education and Prevention Program Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma do not recommend a specific dose or route for magnesium in the infant or pediatric population.

Table 1: Asthma in the Pediatric Patient Assessment Tool

This continuing education activity is approved by EMS World Magazine, an organization accredited by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS), for 1.5 CEUs. To earn your credits, go to www.rapidce.com, or to print and mail a copy, download the test here.

References

1. Henrickson KJ, Hoover S, Kehl KS, Hua W. National disease burden of respiratory viruses detected in children by polymerase chain reaction. Pediatr Infect Dis J 23(Suppl):11, 2004.
2. Centers for Disease Control and Prevention. Respiratory Sycytial Virus Infection: Infection and Incidence. www.cdc.gov/rsv/about/infection.html. Updated January 25, 2010.
3. Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr 143(suppl):S127 -S132, 2003.
4. Mullins JA, Lamonte AC, Bresee JS, Anderson LJ. Substantial variability in community respiratory syncytial virus season timing. Pediatr Infect Dis J 22:857-886, 2003.
5. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289(2):179-186, Jan 8 2003.
6. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 360(6):588-598, Feb 5, 2009.
7. Purcell K, Fergie J. Driscoll Children's Hospital respiratory syncytial virus database: Risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002. Pediatr Infect Dis J 23:418-423, 2004.
8. Welliver RC. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 143:S112-S117, 2003.
9. Navas L, Wang E, de Carvalho V, et al. Improved outcome of respiratory syncytial virus infections in a high-risk hospitalized population of Canadian children. J Pediatr121:348-354, 1992.
10. López-Alarcón M, Villalpando S, Fajardo A. Breastfeeding lowers the frequency and duration of acute respiratory infection and diarrhea in infants under six months of age. J Nutr 127(3):436 -443, 1997.
11. Wright AL, Bauer M, Naylor A, et al. Increasing breastfeeding rates to reduce infant illness at the community level. Pediatrics 101(5):837-844, 1998.
12. Centers for Disease Control and Prevention. Respiratory syncytial virus infection (RSV).
13. Centers for Disease Control and Prevention. 2007 National Health Interview Survey Public Use Data File. www.cdc.gov.
14. Centers for Disease Control and Prevention. National Surveillance for Asthma-United States, 1980-2004. www.cdc.gov/mmwr/preview/mmwrhtml/ss5608a1.htm.
15. Akinbami L. The state of childhood asthma, United States, 1980-2005. Adv Data 381:1, 2006.
16. Geelhoed GC, Landau LI, Le Souef PN. Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma. Ann Emerg Med 23:1236, 1994.
17. Gorelick MH, Stevens MW, Schultz TR, Scribano PV. Performance of a novel clinical score, the Pediatric Asthma Severity Score (PASS), in the evaluation of acute asthma. Acad Emerg Med 11:10, 2004
18. Rodrigo G, Pollack C, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database Systematic Reviews 4:CD002884, 2006.
19. de Klerk A. Humidified high-flow nasal cannula: Is it the new and improved CPAP? Adv Neonatal Care 8:98-106, 2008.
20. Kubicka ZJ, Limauro J, Darnell RA. Heated humidified high-flow nasal cannula therapy: Yet another way to deliver continuous positive airway pressure? Pediatrics 121: 82-88, 2008.
21. Lampland AL, Plumm B, Meyers PA, et al. Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure. J Pediatr 154:177-182, 2009.
22. Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannulae in the management of apnea of prematurity: A comparison with conventional nasal continuous positive airway pressure. Pediatrics 107:1081-1083, 2001.
23. Thia LP, McKenzie SA, Blyth TP, et al. Randomised controlled trial of nasal continuous positive airway pressure in bronchiolitis. Arch Dis Child 93:637-638, 2008.
24. Larrar S, Essouri S, Durand P, et al. Effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis. Archives de Pediatrie 13:1397-1403, 2006.
25. Yong SC, Chen SJ, Boo NY. Incidence of nasal trauma associated with nasal prong versus nasal mask during continuous positive airway pressure treatment in very low birthweight infants: A randomized control study. Arch Dis Child Fetal Neonatal Ed 90:F480-F483, 2005.
26. Schuh S, et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. J Pediatr, 1995.
27. Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med 339:1030, 1998.
28. Watts KD, Goodman DM. Wheezing, Bronchiolitis, and Bronchitis. In: Kliegman: Nelson Textbook of Pediatrics, 18th ed., Saunders, 2007.
29. Rowe BH, et al. Intravenous magnesium sulfate treatment for acute asthma in the emergency department: A systematic review of the literature. Ann Emerg Med 36:181, 2000.
30. Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child 90:74, 2005.

   Scott R. Snyder, BS, NREMT-P, is the EMS education manager for the San Francisco Paramedic Association in San Francisco, CA, where he is responsible for the original and continuing education of EMTs and paramedics. Contact him at scottrsnyder@me.com.

Michael Santiago, DO, EMT-P, is an attending physician in the ED and director of prehospital care at Rochester General Hospital in Rochester, NY. Contact him at ems@rochestergeneral.org.

   Kevin T. Collopy, BA, CCEMT-P, NREMT-P, WEMT, is an educator, e-learning content developer and author of numerous articles and textbook chapters. He is also a flight paramedic for Spirit Ministry Medical Transportation in central Wisconsin and a lead instructor for Wilderness Medical Associates. Contact him at kcollopy@colgatealumni.org.