Pediatric Asthma: An Evidence-Based Practice Study

Childhood asthma is an inflammation of lung’s airways affecting infants and children in nearly all industrialized countries listed as 1 of the top 3 indications of children hospitalizations. As Ferrante and La Grutta (2018) posited it is a chronic respiratory childhood disease and a leading cause of emergency room visits. The inflammation is characterized by reversible and episodic constriction of the airway in response to irritants, infection and environmental allergens. The disease is also provoked by poor air quality, tobacco smoke and exercise. Patel and Teach (2019) elucidated that the condition is immune mediated, multifactorial and complex with a plethora of clinical phenotypes. Childhood asthma precipitates bothersome daily symptoms which disrupt school, sleep, play and sport among toddlers. Missed work, medical care and missed school due to pediatric asthma overburden communities and cost more than $80 billion annually. The condition disproportionately affects children from socioeconomically disadvantaged backgrounds. An evidence based study by Mirra, Montella and Santamaria (2018), indicated that many infants and pre-school children contract bronchial symptoms and recurrent episodes beginning few months of age after birth. Symptoms of pediatric asthma are frequently transient and common in preschool years. An acute asthma attack can manifest as the first episode in undiagnosed children or among infants who have had history of Asthma diagnosis and an uncontrolled malady. 

Irrespective of the array of medical advances in therapy, optimal control of pediatric asthma has not been achieved globally. A study by Ferrante and La Grutta (2018) reported that asthma attacks can be life threatening, increasingly exorbitant to treat and particularly recurrent among unresponsive children. Pediatric Asthma has no treatment as the current medications are only meant to control symptoms and enable patients’ live full and rewarding lives ( Burnset al., 2017) . An array of guidelines have been fronted to support pediatric asthma management by healthcare professionals such as the Global Strategy for Asthma Management and Prevention (GINA). The study explores pediatric asthma in respect to aspects such as morbidity, pathophysiology, clinical presentation, diagnostic criteria and treatment plans using evidence based guidelines. 

Morbidity and Mortality 

Globally, pediatric asthma morbidity and mortality rates have surged over the last two decades due to increased globalization. WHO approximated that there occurs 500,000 hospitalizations annually representing 34.6% due to asthma. According to World Health Organization, current trends have been soaring with approximately 250,000 children dying from Pediatric asthma. Pediatric asthma prevalence soared from 8.7% to 9.4% in 2001 and 2010 respectively and then plummeted in 2016 to 8.3% (NCBI, n.d) . In 2013, juveniles aged 5 to 17 years missed 13.8 million school days equating to an average of 2.6 days per toddler. Between 2002 and 2003, asthma prevalence among children varied widely with 4.3% of the global population reporting a physician’s diagnosis ( Patel & Teach, 2019 ). 4.5% of the population indicated that they were under asthma treatment while 8.6% reported experiencing symptoms of whistling or wheezing in the preceding one year ( Serebrisky & Wiznia, 2019) . The United States registers 1 asthma case in every 12 children whose age range from 0 to 17 years. Between 2010 and 2012, pediatric asthma prevalence plateaued. In black children, asthma incidences rose between 2001 and 2009 and levelled in 2013. An exponential rise was recorded in black children prevalence to 15.7% equivalent to 2.3% increment from 2014 and 2015, a number twice that of white children ( Patel & Teach, 2019 ). The rate even exceeded that recorded by Puerto Rican juveniles who had registered the highest morbidity. Prevalence among children from poverty stricken backgrounds rose between 2001 and 2013 and increased higher to 10.5% in 2016. Center for Disease Control and Prevention reported than by 2018, number of children diagnosed with asthma were 5.5 million representing a 7.5% ( CDCP, 2019) . The number of physician visits with asthma as the primary diagnosis stood at 9.8 million while visits to the emergency room were 1.6 million ( Patel & Teach, 2019 ). In 2015, asthma related fatalities stood at 3,615 with those under 18 years making up 219 of the demises. Death rates among juveniles worldwide vary from 0 to 0.7 per every hundred thousand people. In the United States childhood asthma related deaths has risen in age, sex strata and race. The mortality rate caused by pediatric asthma is more than 17 fatalities per a population of 1 million which equates to 5,000 demises every year. The non-Hispanic blacks have the highest likelihood of dying from pediatric asthma with a fatality rate of more than 200%, which exceeds that of Hispanic whites and 160% more than Hispanics. CDC 2017 data on mortality reported that the United States recorded 3,564 deaths ( CDCP, 2019) . 

Etiology 

A study by Subbarao, Mandhane and Sears (2009), indicated that pediatric asthma presents a multiplicity of heterogeneous phenotypes. The etiology factors for recognized phenotypes range from host, genetic and environmental triggers. Asthma family history and environmental causative agents contribute immensely to the burgeoning of pediatric asthma epidemic. 

Genetic 

Epidemiological studies indicate that genetics are key contributors of development of allergy and asthma. Several genes of moderate effect give rise to risks in range of 1.2-2. Case control studies supplemented by genome wide linkage research have pin pointed over 100 genes and 18 genome regions linked with asthma and allergy in 11 heterogeneous populations. The long chromosomal arms 2, 5, 6, 12 and 13 have consistent replication of genome regions. A recent genome wide linkage research isolated a new gene ORMDL3, whose association with asthma was highly significant with a p  < 10 −12 and confidence interval of 95%, 1.43–2.42 and an odds ratio of 1.84 (Chung, Hathaway & Lew, 2015). The studies found a likely extensive heterogeneity in pediatric asthma genetic basis coupled with an in gene-by-environment relationship. 

Prenatal Etiology Factors 

Prenatal Tobacco Smoke 

Studies have linked early childhood asthma to pre-natal maternal smoking. Exposure to tobacco smoke and decreased airway in infancy has a dose double relation. Prenatal tobacco abuse has a direct relationship with heightened risk of food allergy, cytokine cord blood responses and high nitric oxide concentrations in infants. 

Diet and Nutrition 

Observational studies on dietary interventions paid attention to antioxidants such as zinc and vitamin E and focussed on anti-inflammatory foods like mega-3 fatty acids. The prenatal nutrient studies indicated that higher fish consumption during pregnancy lowers atopic disease risk up to 6 years. Likewise, higher levels of zinc and vitamin E reduces likelihood of wheezing up to age 5 (Subbarao et al., 2009). During pregnancy, the studies showed no protective effect against manifestation of atopic disease in infants for maternal diet that foregone foods such as eggs and cow milk. An inverse correlation manifested between maternal vitamin D levels and wheezing in childhood phase but with zero association with atopy or akin symptoms in later years. 

Stress 

Stress during maternal period acts through controlling an infant’s hypothalamic pituitary adrenal axis to lower levels of cortisol which may impact allergic phenotype development. Studies have showcased a relationship between care giver stress during an infant’s life and increased amounts of immunoglobulin E in the juvenile and early wheezing. 

Use of Antibiotic 

Previous studies have examined the relationship between development of atopic disease in infants and prenatal antibiotic treatment. Longitudinal cohort researches examined use of any antibiotic and showed a significant likelihood of developing asthma and persistent wheeze during infancy. 

Mode of Delivery 

Emergency caesarean section increased the risk of developing atopy among infants 2 to 3 times relative to normal delivery; however, elective caesarean section exhibited no such association (Sevelsted, Stokholm, & Bisgaaard, 2016). The longitudinal studies cited reasons such as microflora infant’s gut differences and maternal stress linked with different delivery modes. 

Childhood risk factors 

Breastfeeding 

Although the association between breastfeeding and development of asthma in infants remain controversial, some studies have shown a degree of protection while others reported increased risk of allergy among breastfed children. Accumulated meta-analysis data indicate that 3 months exclusive breastfeeding decreases risk of developing asthma among children aged 2 to 5 years with the most conspicuous effect noted among children whose parents had a previously atopy history. The difference in result interpretation however occurs in distinguishing between childhood viral wheezing and that caused by development of atopic asthma. A longitudinal study by Ramratnam, Bacharier and Guilbert (2017) reported that breastfeeding immensely contributed to development of atopic asthma later in childhood with those children whose parents had a previous atopy history having the greatest influence. 

Sex and Gender 

Development of pediatric asthma based on a child’s sex is time dependent. Until 13 to 14 years, boys experience a high asthma prevalence and incidence in relation to girls. Several longitudinal studies on puberty have indicated that adolescents and young adult females have a relatively high risk of asthma incidence and a greater proportion of asthma remission among males. Prior to attaining 12 years, boys report high cases of hospital asthma admission than girls. Males during childhood experience common and severe cases of airway hyper-responsiveness than females, with girls being at risk of having an increased risk of airway hyper-responsiveness during adolescence. 

Pathophysiology 

Pediatric asthma is highly complex with an immune mediation which manifests through obstruction of lower airway due to muscle constriction. Numerous inflammatory pathways to swelling of airways lead to myriad clinical phenotypes of childhood asthma. Longitudinal studies have isolated three distinct phenotypes linked to wheezing; non-atopic wheezing, transient wheezing and atopy ( Galowitz & Chang, 2015) . 

Airway inflammation associated to asthma is precipitated a plethora of sell subtypes which lead to hyper-responsive airways, eventually constricting flow of air and triggering variable symptoms. Airway bronchoconstriction precedes airway edema which is followed by exaggerated mucus production thereby triggering airway hyper-responsiveness and acute alterations in airway epithelium (( Patel & Teach, 2019 ). A variety of chemokines and cytokines mediate airway inflammation. Mast cells, eosinophils and lymphocytes produce cytokines. T-helper (Th)2 lymphocytes excrete proinflammatory cytokines such as IL-13, IL-4 and IL-5 which catalyzes acute allergic asthma inflammation. Chronic asthma inflammation is triggered by Th1 and Th2 lymphocytes imbalance. Neutrophils, eosinophils and Th2 lymphocytes cells are recruited by proteins such as chemokines. Mast cells and eosinophils catalyze asthma pathogenesis by excreting leukotrienes and proinflammatory cytokines which cause bronchoconstriction ( Galowitz & Chang, 2015) . Infectious, environmental and infectious causative agents such as allergens, cold air, and chemical, agents target airway epithelium via increased cytokines ultimately causing injury as indicated in figure 1 above. The viral infections coupled with airborne allergens trigger a biphasic reaction which precipitates asthma attack. IgE-mediated reaction to an allergen causes degranulation of basophils and mast cells ultimately spurring excretion of chemokines and precipitation of bronchospasm ( Mirra, Montella & Santamaria, 2018) . Structural alterations in the epithelium airway on a cellular level also characterizes pediatric asthma. Occurrence of airway remodelling is linked with epithelium structural changes such as mucus gland hyperplasia, epithelial membrane thickening, fibrotic alterations and angiogenesis. 

Diagnostic Testing 

Peak Flows 

Peak expiratory flow (PEF) is an inexpensive diagnostic method that provides children families with objective data to commence medications. The method uses a pre-determined child’s personal best to guide acute management. A personal best that falls below 80% prompts caregivers to commence rescue treatment using asthma action plan ( Matsunaga et al. 2015) . 70% to 80% of a child’s personal best equates to yellow zone management while 40 % to 70 % indicates red zone management ( Patel & Teach, 2019 ). 

Spirometry/PFT 

The diagnostic test measures the amount of air a child can take out and how quickly which is a lung function test. Spirometry documents obstruction or limitation of respiratory flow with reversibility. A less than 0.80 FEV 1% indicates airflow obstruction which confirms asthma. A FEV 1% that exceeds 0.8 indicates normal respiration. Periodic spirometry lung function measurements are critical in maintaining healthy lung function. 

Methacholine Challenge 

The test includes brochoprovocation diagnostics such as methacholine test. Brocho-provocation measures how a child’s lungs responds to provocation such as inhaling of a drug that triggers mild narrowing of airways ( McGeachie et al., 2016) . The test is associated to greater negative predictive potency which makes it perform well in ruling out asthma. 

Clinical Presentation 

Wheezing characterized by high pitched sound generated by turbulence of airflow is a common pediatric asthma clinical presentation. In its mildest form, the wheezing sound is end expiratory. Increased severity of wheezing lasts through the span of expiration. According to Bass (2019) during severe episodes, severe obstruction of airflow associated with respiratory muscle lethargy and airway narrowing make wheezing absent. Wheezing albeit common does not necessary indicate pediatric asthma diagnosis as it can be linked to cystic fibrosis and heart failure. Children with inducible laryngeal obstruction present a monophonic wheeze that differs from polyphonic wheeze in asthma. Patients with extreme airway collapse, tracheomalacia or brochomalacia may also present monophonic wheeze detected over large airways ( Smit et al., 2015) . Wheezing may also clinically present after exercise in induced bronchoconstriction. Wheezing in nocturia asthma presents itself during the night only. 

Persistent and continuous coughing particularly in cases of nocturnal asthma or exercise induced test may be the only symptom of pediatric asthma. The persistent cough indicative of pediatric asthma is usually non-paroxysmal and non-productive. Coughing during the day and after mid-night among children would be a manifestation of nocturnal asthma. In exercise induced testing, chest aches or chest tightness may manifest with or without asthmatic symptoms. Additional clinical presentation associated with pediatric asthma include history of recurrent pneumonia, chest rattling, recurrent coup, bronchiolitis and recurrent bronchitis ( Riverin, Maguire & Li, 2015) . Most children previously diagnosed with recurrent bronchitis are also asthmatic. Longitudinal studies have indicated that children with recurrent pneumonia also present asthma as a common underlying diagnosis. 

Tachypnea, nasal flaring, use of accessory muscles and retractions are clinical presentations of pediatric asthma. Tachypnea is characterized by rapid, shallow and fast breathing. Patients with acute pediatric asthma present tachycardia and right hear strain. As Zeretzke-Bien (2018) asserts, tachycardia makes a patient’s heart exceed more than 100 heart beats in one minute. Severely asthmatic children should be subjected to ECG monitoring to test for presence of sinus tachycardia. Cyanosis although rare is a clinical presentation that can indicate pediatric asthma. Cyanosis manifests though presence of bluish hands or feet discoloration due to limited oxygen levels or difficulties from receiving oxygenated blood from red blood cells. Following restriction of air entering a person’s lugs due to obstruction of airways, cyanosis may manifest. Restriction of air constrains a person’s body ability to absorb optimal oxygen levels necessary to oxygenate blood and deliver oxygen to rest organs of the body. 

The clinician examining the child for possible asthma diagnosis should determine the symptoms pattern on whether the clinical presentation is perennial or seasonal, day time or time, onset or duration, contionous or intermittent. The clinical symptoms presentation among children manifest early in life with the first sign incidence occurring in juveniles younger than 4 years. A study by AL-Eryani et al., (2016) indicated that children who exhibited asthmatic symptoms during their first year of life were 36% cases, between 1 to 3 years 46.0% and 18.0% after the 3 rd year. The finding agreed with a research by Beasley, Semprini and Mitchell (2015) who posited that age of onset of asthma before 4 years had a mark of 86% while nearly half of pediatric asthma cases manifested during the infants first year of life. 

Diagnostic Criteria and Management 

Routine screening is a clinical preventative measure that plays a crucial role in early detection and slowing progression of pediatric asthma. Children can undergo asthma screening such as spirometry, challenge tests and exhaled nitric oxide diagnostic. Annual examination of children exposed to allergens is a recommended clinical preventative practice. Routine examination by a clinician entails checking of throat, skin, ears, lungs, nose, head and eyes as a baseline and on annual basis. Pulmonary function testing following the American Thoracic Society protocol is vital in determining if the pulmonary function is normal or abnormal. Early vaccination for pneumonia and influenza is vital in preventing the two diseases and also plays a pivotal role in averting cases of asthma flare ups. 

Treatment Plan 

The Global Strategy for Asthma Management and Prevention guidelines issued by GINA and the American Thoracic Society guidelines are widely accepted in treating pediatric asthma. Pharmacological treatment options entail using reliever medications which permit symptoms relief for a short while. The pharmacological medications are also used during asthma exacerbation and in preventing exercise induced bronchoconstriction. The drug classifications mostly recommended include corticosteroids, beta-2 adrenergic agonists and leukotriene modifiers ( Tesse et al., 2018) . Pharmacological management of pediatric asthma should follow a step wise approach as indicated by table 1.1. If control is not realized after the first step of treatment within 3 months stepping up is recommended after therapy, associated comorbidities and environmental factors considerations. 

Step 1 treatment is effected using inhaled short acting beta2-antagonists only, commonly salbutamol. SABAs provide relief for acute asthma symptoms among patients with normal lung function but with occasional daytime symptoms. The second line relievers include anticholinergic agents mainly ipratropium although they are less efficacious than SABA but produce synergistic impact when supplemented with SABA during acute exercibation. Long term asthma control is realized through uptake of inhaled corticosteroids. ISC therapeutic doses in addition to SABA are recommended for long term control among children. ICS starting dose should be equal to or less than 200 micrograms administered twice daily ( Medscape.com, 2019) . The table indicates low, medium and high doses of inhaled corticosteroids among asthmatic adolescents and children as recommended by national guidelines. 

Long acting beta-2 adrenergic agonists (LABA) for example formoterol and salmeterol are recommended with combination of ICS to improve asthma outcomes. LABA ought to be administered in fixed dose combinations but not as a monotherapy for pediatric asthma. Leukotriene receptor antagonists (LTRAs) treatment is recommended to hinder airway muscle stiffening and impede excretion mucus triggered by leukotriens. International treatment guidelines recommend usage of LTRA as a second choice immunotherapy after a low dosage of ICS. LTRAs also serve as add on medications in improving pulmonary function in addition to ICS ( Tesse et al., 2018) . Omalizumab drugs such as anti-immunoglobulin E are recommended for adolescents with impaired lung function, allergic asthma and those with allergen Ige-mediated sensitivity. Immunotherapy treatment plan using sublingual allergen and subcutaneous immunotherapy have been proved to be efficacious in managing bronchia hyper -reactivity and hypersensitivity among children who are unresponsive to preventative options such as ICS. 

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